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  • 51. Borry, Pascal
    et al.
    Rusu, Olivia
    Howard, Heidi C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Genetic testing: anonymity of sperm donors under threat.2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 496, no 7444, p. 169-Article in journal (Refereed)
  • 52. Botella, Hector
    et al.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Dorka, Markus
    Ahlberg, Per Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Janvier, Philippe
    Jaws and teeth of the earliest bony fishes2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 448, no 7153, p. 583-586Article in journal (Refereed)
    Abstract [en]

    Extant jawed vertebrates, or gnathostomes, fall into two major monophyletic groups, namely chondrichthyans (cartilaginous fishes) and osteichthyans (bony fishes and tetrapods). Fossil representatives of the osteichthyan crown group are known from the latest Silurian period, 418 million years (Myr) ago, to the present. By contrast, stem chondrichthyans and stem osteichthyans are still largely unknown. Two extinct Palaeozoic groups, the acanthodians and placoderms, may fall into these stem groups or the common stem group of gnathostomes, but their relationships and monophyletic status are both debated. Here we report unambiguous evidence for osteichthyan characters in jaw bones referred to the late Silurian (423–416-Myr-old) fishes Andreolepis hedei and Lophosteus superbus, long known from isolated bone fragments, scales and teeth, and whose affinities to, or within, osteichthyans have been debated1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. The bones are a characteristic osteichthyan maxillary and dentary, but the organization of the tooth-like denticles they bear differs from the large, conical teeth of crown-group osteichthyans, indicating that they can be assigned to the stem group. Andreolepis and Lophosteus are thus not only the oldest but also the most phylogenetically basal securely identified osteichthyans known so far.

  • 53. Brawand, David
    et al.
    Wagner, Catherine E.
    Li, Yang I.
    Malinsky, Milan
    Keller, Irene
    Fan, Shaohua
    Simakov, Oleg
    Ng, Alvin Y.
    Lim, Zhi Wei
    Bezault, Etienne
    Turner-Maier, Jason
    Johnson, Jeremy
    Alcazar, Rosa
    Noh, Hyun Ji
    Russell, Pamela
    Aken, Bronwen
    Alfoeldi, Jessica
    Amemiya, Chris
    Azzouzi, Naoual
    Baroiller, Jean-Francois
    Barloy-Hubler, Frederique
    Berlin, Aaron
    Bloomquist, Ryan
    Carleton, Karen L.
    Conte, Matthew A.
    D'Cotta, Helena
    Eshel, Orly
    Gaffney, Leslie
    Galibert, Francis
    Gante, Hugo F.
    Gnerre, Sante
    Greuter, Lucie
    Guyon, Richard
    Haddad, Natalie S.
    Haerty, Wilfried
    Harris, Rayna M.
    Hofmann, Hans A.
    Hourlier, Thibaut
    Hulata, Gideon
    Jaffe, David B.
    Lara, Marcia
    Lee, Alison P.
    MacCallum, Iain
    Mwaiko, Salome
    Nikaido, Masato
    Nishihara, Hidenori
    Ozouf-Costaz, Catherine
    Penman, David J.
    Przybylski, Dariusz
    Rakotomanga, Michaelle
    Renn, Suzy C. P.
    Ribeiro, Filipe J.
    Ron, Micha
    Salzburger, Walter
    Sanchez-Pulido, Luis
    Santos, M. Emilia
    Searle, Steve
    Sharpe, Ted
    Swofford, Ross
    Tan, Frederick J.
    Williams, Louise
    Young, Sarah
    Yin, Shuangye
    Okada, Norihiro
    Kocher, Thomas D.
    Miska, Eric A.
    Lander, Eric S.
    Venkatesh, Byrappa
    Fernald, Russell D.
    Meyer, Axel
    Ponting, Chris P.
    Streelman, J. Todd
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Seehausen, Ole
    Di Palma, Federica
    The genomic substrate for adaptive radiation in African cichlid fish2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 513, no 7518, p. 375-381Article in journal (Refereed)
    Abstract [en]

    Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand themolecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.

  • 54.
    Brazeau, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    The braincase and jaws of a Devonian “acanthodian” and modern gnathostome origins2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 457, no 7227, p. 305-308Article in journal (Refereed)
    Abstract [en]

    Modern gnathostomes ( jawed vertebrates) emerged in the early Palaeozoic era(1), but this event remains unclear owing to a scant early fossil record. The exclusively Palaeozoic 'acanthodians' are possibly the earliest(2,3) gnathostome group and exhibit amosaic of shark- and bony fish- like characters that has long given them prominence in discussions of early gnathostome evolution(1). Their relationships with modern gnathostomes have remained mysterious, partly because their un- mineralized endoskeletons rarely fossilized. Here I present the first- known braincase of an Early Devonian (approximately 418-412 Myr BP) acanthodian, Ptomacanthus anglicus(4), and re- evaluate the interrelationships of basal gnathostomes. Acanthodian braincases have previously been represented by a single genus, Acanthodes(5), which occurs more than 100 million years later in the fossil record. The braincase of Ptomacanthus differs radically from the osteichthyan- like braincase of Acanthodes(5) in exhibiting several plesiomorphic features shared with placoderms(6,7) and some early chondrichthyans(8,9). Most striking is its extremely short sphenoid region and its jaw suspension, which displays features intermediate between some Palaeozoic chondrichthyans and osteichthyans. Phylogenetic analysis resolves Ptomacanthus as either the most basal chondrichthyan or as the sister group of all living gnathostomes. These new data alter earlier conceptions of basal gnathostome phylogeny and thus help to provide a more detailed picture of the acquisition of early gnathostome characters.

  • 55.
    Budd, Graham E.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Palaeontology: Cambrian nervous wrecks2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 490, no 7419, p. 180-181Article in journal (Other academic)
  • 56.
    Budd, Graham E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Telford, Maximilian J.
    The origin and evolution of arthropods2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 457, no 7231, p. 812-817Article, review/survey (Refereed)
    Abstract [en]

    The past two decades have witnessed profound changes in our understanding of the evolution of arthropods. Many of these insights derive from the adoption of molecular methods by systematists and developmental biologists, prompting a radical reordering of the relationships among extant arthropod classes and their closest non- arthropod relatives, and shedding light on the developmental basis for the origins of key characteristics. A complementary source of data is the discovery of fossils from several spectacular Cambrian faunas. These fossils form well- characterized groupings, making the broad pattern of Cambrian arthropod systematics increasingly consensual.

  • 57. Burstein, Roy
    et al.
    Henry, Nathaniel J
    Collison, Michael L
    Marczak, Laurie B
    Sligar, Amber
    Watson, Stefanie
    Marquez, Neal
    Abbasalizad-Farhangi, Mahdieh
    Abbasi, Masoumeh
    Abd-Allah, Foad
    Abdoli, Amir
    Abdollahi, Mohammad
    Abdollahpour, Ibrahim
    Abdulkader, Rizwan Suliankatchi
    Abrigo, Michael R M
    Acharya, Dilaram
    Adebayo, Oladimeji M
    Adekanmbi, Victor
    Adham, Davoud
    Afshari, Mahdi
    Aghaali, Mohammad
    Ahmadi, Keivan
    Ahmadi, Mehdi
    Ahmadpour, Ehsan
    Ahmed, Rushdia
    Akal, Chalachew Genet
    Akinyemi, Joshua O
    Alahdab, Fares
    Alam, Noore
    Alamene, Genet Melak
    Alene, Kefyalew Addis
    Alijanzadeh, Mehran
    Alinia, Cyrus
    Alipour, Vahid
    Aljunid, Syed Mohamed
    Almalki, Mohammed J
    Al-Mekhlafi, Hesham M
    Altirkawi, Khalid
    Alvis-Guzman, Nelson
    Amegah, Adeladza Kofi
    Amini, Saeed
    Amit, Arianna Maever Loreche
    Anbari, Zohreh
    Androudi, Sofia
    Anjomshoa, Mina
    Ansari, Fereshteh
    Antonio, Carl Abelardo T
    Arabloo, Jalal
    Arefi, Zohreh
    Aremu, Olatunde
    Armoon, Bahram
    Arora, Amit
    Artaman, Al
    Asadi, Anvar
    Asadi-Aliabadi, Mehran
    Ashraf-Ganjouei, Amir
    Assadi, Reza
    Ataeinia, Bahar
    Atre, Sachin R
    Quintanilla, Beatriz Paulina Ayala
    Ayanore, Martin Amogre
    Azari, Samad
    Babaee, Ebrahim
    Babazadeh, Arefeh
    Badawi, Alaa
    Bagheri, Soghra
    Bagherzadeh, Mojtaba
    Baheiraei, Nafiseh
    Balouchi, Abbas
    Barac, Aleksandra
    Bassat, Quique
    Baune, Bernhard T
    Bayati, Mohsen
    Bedi, Neeraj
    Beghi, Ettore
    Behzadifar, Masoud
    Behzadifar, Meysam
    Belay, Yared Belete
    Bell, Brent
    Bell, Michelle L
    Berbada, Dessalegn Ajema
    Bernstein, Robert S
    Bhattacharjee, Natalia V
    Bhattarai, Suraj
    Bhutta, Zulfiqar A
    Bijani, Ali
    Bohlouli, Somayeh
    Breitborde, Nicholas J K
    Britton, Gabrielle
    Browne, Annie J
    Nagaraja, Sharath Burugina
    Busse, Reinhard
    Butt, Zahid A
    Car, Josip
    Cárdenas, Rosario
    Castañeda-Orjuela, Carlos A
    Cerin, Ester
    Chanie, Wagaye Fentahun
    Chatterjee, Pranab
    Chu, Dinh-Toi
    Cooper, Cyrus
    Costa, Vera M
    Dalal, Koustuv
    Dandona, Lalit
    Dandona, Rakhi
    Daoud, Farah
    Daryani, Ahmad
    Das Gupta, Rajat
    Davis, Ian
    Davis Weaver, Nicole
    Davitoiu, Dragos Virgil
    De Neve, Jan-Walter
    Demeke, Feleke Mekonnen
    Demoz, Gebre Teklemariam
    Deribe, Kebede
    Desai, Rupak
    Deshpande, Aniruddha
    Desyibelew, Hanna Demelash
    Dey, Sagnik
    Dharmaratne, Samath Dhamminda
    Dhimal, Meghnath
    Diaz, Daniel
    Doshmangir, Leila
    Duraes, Andre R
    Dwyer-Lindgren, Laura
    Earl, Lucas
    Ebrahimi, Roya
    Ebrahimpour, Soheil
    Effiong, Andem
    Eftekhari, Aziz
    Ehsani-Chimeh, Elham
    El Sayed, Iman
    El Sayed Zaki, Maysaa
    El Tantawi, Maha
    El-Khatib, Ziad
    Emamian, Mohammad Hassan
    Enany, Shymaa
    Eskandarieh, Sharareh
    Eyawo, Oghenowede
    Ezalarab, Maha
    Faramarzi, Mahbobeh
    Fareed, Mohammad
    Faridnia, Roghiyeh
    Faro, Andre
    Fazaeli, Ali Akbar
    Fazlzadeh, Mehdi
    Fentahun, Netsanet
    Fereshtehnejad, Seyed-Mohammad
    Fernandes, João C
    Filip, Irina
    Fischer, Florian
    Foigt, Nataliya A
    Foroutan, Masoud
    Francis, Joel Msafiri
    Fukumoto, Takeshi
    Fullman, Nancy
    Gallus, Silvano
    Gebre, Destallem Gebremedhin
    Gebrehiwot, Tsegaye Tewelde
    Gebremeskel, Gebreamlak Gebremedhn
    Gessner, Bradford D
    Geta, Birhanu
    Gething, Peter W
    Ghadimi, Reza
    Ghadiri, Keyghobad
    Ghajarzadeh, Mahsa
    Ghashghaee, Ahmad
    Gill, Paramjit Singh
    Gill, Tiffany K
    Golding, Nick
    Gomes, Nelson G M
    Gona, Philimon N
    Gopalani, Sameer Vali
    Gorini, Giuseppe
    Goulart, Bárbara Niegia Garcia
    Graetz, Nicholas
    Greaves, Felix
    Green, Manfred S
    Guo, Yuming
    Haj-Mirzaian, Arvin
    Haj-Mirzaian, Arya
    Hall, Brian James
    Hamidi, Samer
    Haririan, Hamidreza
    Haro, Josep Maria
    Hasankhani, Milad
    Hasanpoor, Edris
    Hasanzadeh, Amir
    Hassankhani, Hadi
    Hassen, Hamid Yimam
    Hegazy, Mohamed I
    Hendrie, Delia
    Heydarpour, Fatemeh
    Hird, Thomas R
    Hoang, Chi Linh
    Hollerich, Gillian
    Rad, Enayatollah Homaie
    Hoseini-Ghahfarokhi, Mojtaba
    Hossain, Naznin
    Hosseini, Mostafa
    Hosseinzadeh, Mehdi
    Hostiuc, Mihaela
    Hostiuc, Sorin
    Househ, Mowafa
    Hsairi, Mohamed
    Ilesanmi, Olayinka Stephen
    Imani-Nasab, Mohammad Hasan
    Iqbal, Usman
    Irvani, Seyed Sina Naghibi
    Islam, Nazrul
    Islam, Sheikh Mohammed Shariful
    Jürisson, Mikk
    Balalami, Nader Jafari
    Jalali, Amir
    Javidnia, Javad
    Jayatilleke, Achala Upendra
    Jenabi, Ensiyeh
    Ji, John S
    Jobanputra, Yash B
    Johnson, Kimberly
    Jonas, Jost B
    Shushtari, Zahra Jorjoran
    Jozwiak, Jacek Jerzy
    Kabir, Ali
    Kahsay, Amaha
    Kalani, Hamed
    Kalhor, Rohollah
    Karami, Manoochehr
    Karki, Surendra
    Kasaeian, Amir
    Kassebaum, Nicholas J
    Keiyoro, Peter Njenga
    Kemp, Grant Rodgers
    Khabiri, Roghayeh
    Khader, Yousef Saleh
    Khafaie, Morteza Abdullatif
    Khan, Ejaz Ahmad
    Khan, Junaid
    Khan, Muhammad Shahzeb
    Khang, Young-Ho
    Khatab, Khaled
    Khater, Amir
    Khater, Mona M
    Khatony, Alireza
    Khazaei, Mohammad
    Khazaei, Salman
    Khazaei-Pool, Maryam
    Khubchandani, Jagdish
    Kianipour, Neda
    Kim, Yun Jin
    Kimokoti, Ruth W
    Kinyoki, Damaris K
    Kisa, Adnan
    Kisa, Sezer
    Kolola, Tufa
    Kosen, Soewarta
    Koul, Parvaiz A
    Koyanagi, Ai
    Kraemer, Moritz U G
    Krishan, Kewal
    Krohn, Kris J
    Kugbey, Nuworza
    Kumar, G Anil
    Kumar, Manasi
    Kumar, Pushpendra
    Kuupiel, Desmond
    Lacey, Ben
    Lad, Sheetal D
    Lami, Faris Hasan
    Larsson, Anders O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lee, Paul H
    Leili, Mostafa
    Levine, Aubrey J
    Li, Shanshan
    Lim, Lee-Ling
    Listl, Stefan
    Longbottom, Joshua
    Lopez, Jaifred Christian F
    Lorkowski, Stefan
    Magdeldin, Sameh
    Abd El Razek, Hassan Magdy
    Abd El Razek, Muhammed Magdy
    Majeed, Azeem
    Maleki, Afshin
    Malekzadeh, Reza
    Malta, Deborah Carvalho
    Mamun, Abdullah A
    Manafi, Navid
    Manda, Ana-Laura
    Mansourian, Morteza
    Martins-Melo, Francisco Rogerlândio
    Masaka, Anthony
    Massenburg, Benjamin Ballard
    Maulik, Pallab K
    Mayala, Benjamin K
    Mazidi, Mohsen
    McKee, Martin
    Mehrotra, Ravi
    Mehta, Kala M
    Meles, Gebrekiros Gebremichael
    Mendoza, Walter
    Menezes, Ritesh G
    Meretoja, Atte
    Meretoja, Tuomo J
    Mestrovic, Tomislav
    Miller, Ted R
    Miller-Petrie, Molly K
    Mills, Edward J
    Milne, George J
    Mini, G K
    Mir, Seyed Mostafa
    Mirjalali, Hamed
    Mirrakhimov, Erkin M
    Mohamadi, Efat
    Mohammad, Dara K
    Darwesh, Aso Mohammad
    Mezerji, Naser Mohammad Gholi
    Mohammed, Ammas Siraj
    Mohammed, Shafiu
    Mokdad, Ali H
    Molokhia, Mariam
    Monasta, Lorenzo
    Moodley, Yoshan
    Moosazadeh, Mahmood
    Moradi, Ghobad
    Moradi, Masoud
    Moradi, Yousef
    Moradi-Lakeh, Maziar
    Moradinazar, Mehdi
    Moraga, Paula
    Morawska, Lidia
    Mosapour, Abbas
    Mousavi, Seyyed Meysam
    Mueller, Ulrich Otto
    Muluneh, Atalay Goshu
    Mustafa, Ghulam
    Nabavizadeh, Behnam
    Naderi, Mehdi
    Nagarajan, Ahamarshan Jayaraman
    Nahvijou, Azin
    Najafi, Farid
    Nangia, Vinay
    Ndwandwe, Duduzile Edith
    Neamati, Nahid
    Negoi, Ionut
    Negoi, Ruxandra Irina
    Ngunjiri, Josephine W
    Thi Nguyen, Huong Lan
    Nguyen, Long Hoang
    Nguyen, Son Hoang
    Nielsen, Katie R
    Ningrum, Dina Nur Anggraini
    Nirayo, Yirga Legesse
    Nixon, Molly R
    Nnaji, Chukwudi A
    Nojomi, Marzieh
    Noroozi, Mehdi
    Nosratnejad, Shirin
    Noubiap, Jean Jacques
    Motlagh, Soraya Nouraei
    Ofori-Asenso, Richard
    Ogbo, Felix Akpojene
    Oladimeji, Kelechi E
    Olagunju, Andrew T
    Olfatifar, Meysam
    Olum, Solomon
    Olusanya, Bolajoko Olubukunola
    Oluwasanu, Mojisola Morenike
    Onwujekwe, Obinna E
    Oren, Eyal
    Ortega-Altamirano, Doris D V
    Ortiz, Alberto
    Osarenotor, Osayomwanbo
    Osei, Frank B
    Osgood-Zimmerman, Aaron E
    Otstavnov, Stanislav S
    Owolabi, Mayowa Ojo
    P A, Mahesh
    Pagheh, Abdol Sattar
    Pakhale, Smita
    Panda-Jonas, Songhomitra
    Pandey, Animika
    Park, Eun-Kee
    Parsian, Hadi
    Pashaei, Tahereh
    Patel, Sangram Kishor
    Pepito, Veincent Christian Filipino
    Pereira, Alexandre
    Perkins, Samantha
    Pickering, Brandon V
    Pilgrim, Thomas
    Pirestani, Majid
    Piroozi, Bakhtiar
    Pirsaheb, Meghdad
    Plana-Ripoll, Oleguer
    Pourjafar, Hadi
    Puri, Parul
    Qorbani, Mostafa
    Quintana, Hedley
    Rabiee, Mohammad
    Rabiee, Navid
    Radfar, Amir
    Rafiei, Alireza
    Rahim, Fakher
    Rahimi, Zohreh
    Rahimi-Movaghar, Vafa
    Rahimzadeh, Shadi
    Rajati, Fatemeh
    Raju, Sree Bhushan
    Ramezankhani, Azra
    Ranabhat, Chhabi Lal
    Rasella, Davide
    Rashedi, Vahid
    Rawal, Lal
    Reiner, Robert C
    Renzaho, Andre M N
    Rezaei, Satar
    Rezapour, Aziz
    Riahi, Seyed Mohammad
    Ribeiro, Ana Isabel
    Roever, Leonardo
    Roro, Elias Merdassa
    Roser, Max
    Roshandel, Gholamreza
    Roshani, Daem
    Rostami, Ali
    Rubagotti, Enrico
    Rubino, Salvatore
    Sabour, Siamak
    Sadat, Nafis
    Sadeghi, Ehsan
    Saeedi, Reza
    Safari, Yahya
    Safari-Faramani, Roya
    Safdarian, Mahdi
    Sahebkar, Amirhossein
    Salahshoor, Mohammad Reza
    Salam, Nasir
    Salamati, Payman
    Salehi, Farkhonde
    Zahabi, Saleh Salehi
    Salimi, Yahya
    Salimzadeh, Hamideh
    Salomon, Joshua A
    Sambala, Evanson Zondani
    Samy, Abdallah M
    Santric Milicevic, Milena M
    Jose, Bruno Piassi Sao
    Saraswathy, Sivan Yegnanarayana Iyer
    Sarmiento-Suárez, Rodrigo
    Sartorius, Benn
    Sathian, Brijesh
    Saxena, Sonia
    Sbarra, Alyssa N
    Schaeffer, Lauren E
    Schwebel, David C
    Sepanlou, Sadaf G
    Seyedmousavi, Seyedmojtaba
    Shaahmadi, Faramarz
    Shaikh, Masood Ali
    Shams-Beyranvand, Mehran
    Shamshirian, Amir
    Shamsizadeh, Morteza
    Sharafi, Kiomars
    Sharif, Mehdi
    Sharif-Alhoseini, Mahdi
    Sharifi, Hamid
    Sharma, Jayendra
    Sharma, Rajesh
    Sheikh, Aziz
    Shields, Chloe
    Shigematsu, Mika
    Shiri, Rahman
    Shiue, Ivy
    Shuval, Kerem
    Siddiqi, Tariq J
    Silva, João Pedro
    Singh, Jasvinder A
    Sinha, Dhirendra Narain
    Sisay, Malede Mequanent
    Sisay, Solomon
    Sliwa, Karen
    Smith, David L
    Somayaji, Ranjani
    Soofi, Moslem
    Soriano, Joan B
    Sreeramareddy, Chandrashekhar T
    Sudaryanto, Agus
    Sufiyan, Mu'awiyyah Babale
    Sykes, Bryan L
    Sylaja, P N
    Tabarés-Seisdedos, Rafael
    Tabb, Karen M
    Tabuchi, Takahiro
    Taveira, Nuno
    Temsah, Mohamad-Hani
    Terkawi, Abdullah Sulieman
    Tessema, Zemenu Tadesse
    Thankappan, Kavumpurathu Raman
    Thirunavukkarasu, Sathish
    To, Quyen G
    Tovani-Palone, Marcos Roberto
    Tran, Bach Xuan
    Tran, Khanh Bao
    Ullah, Irfan
    Usman, Muhammad Shariq
    Uthman, Olalekan A
    Vahedian-Azimi, Amir
    Valdez, Pascual R
    van Boven, Job F M
    Vasankari, Tommi Juhani
    Vasseghian, Yasser
    Veisani, Yousef
    Venketasubramanian, Narayanaswamy
    Violante, Francesco S
    Vladimirov, Sergey Konstantinovitch
    Vlassov, Vasily
    Vos, Theo
    Vu, Giang Thu
    Vujcic, Isidora S
    Waheed, Yasir
    Wakefield, Jon
    Wang, Haidong
    Wang, Yafeng
    Wang, Yuan-Pang
    Ward, Joseph L
    Weintraub, Robert G
    Weldegwergs, Kidu Gidey
    Weldesamuel, Girmay Teklay
    Westerman, Ronny
    Wiysonge, Charles Shey
    Wondafrash, Dawit Zewdu
    Woyczynski, Lauren
    Wu, Ai-Min
    Xu, Gelin
    Yadegar, Abbas
    Yamada, Tomohide
    Yazdi-Feyzabadi, Vahid
    Yilgwan, Christopher Sabo
    Yip, Paul
    Yonemoto, Naohiro
    Lebni, Javad Yoosefi
    Younis, Mustafa Z
    Yousefifard, Mahmoud
    Yousof, Hebat-Allah Salah A
    Yu, Chuanhua
    Yusefzadeh, Hasan
    Zabeh, Erfan
    Moghadam, Telma Zahirian
    Bin Zaman, Sojib
    Zamani, Mohammad
    Zandian, Hamed
    Zangeneh, Alireza
    Zerfu, Taddese Alemu
    Zhang, Yunquan
    Ziapour, Arash
    Zodpey, Sanjay
    Murray, Christopher J L
    Hay, Simon I
    Mapping 123 million neonatal, infant and child deaths between 2000 and 2017.2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 574, no 7778, p. 353-358Article in journal (Refereed)
    Abstract [en]

    Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

  • 58.
    Carlsbecker, Annelie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Physiological Botany.
    Lee, Ji-Young
    Roberts, Christina J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Physiological Botany.
    Dettmer, Jan
    Lehesranta, Satu
    Zhou, Jing
    Lindgren, Ove
    Moreno-Risueno, Miguel A.
    Vatén, Anne
    Thitamadee, Siripong
    Campilho, Ana
    Sebastian, Jose
    Bowman, John L.
    Helariutta, Yka
    Benfey, Philip N.
    Cell signalling by microRNA165/6 directs gene dose-dependent root cell fate2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 465, no 7296, p. 316-321Article in journal (Refereed)
    Abstract [en]

    A key question in developmental biology is how cells exchange positional information for proper patterning during organ development. In plant roots the radial tissue organization is highly conserved with a central vascular cylinder in which two water conducting cell types, protoxylem and metaxylem, are patterned centripetally. We show that this patterning occurs through crosstalk between the vascular cylinder and the surrounding endodermis mediated by cell-to-cell movement of a transcription factor in one direction and microRNAs in the other. SHORT ROOT, produced in the vascular cylinder, moves into the endodermis to activate SCARECROW. Together these transcription factors activate MIR165a and MIR166b. Endodermally produced microRNA165/6 then acts to degrade its target mRNAs encoding class III homeodomain-leucine zipper transcription factors in the endodermis and stele periphery. The resulting differential distribution of target mRNA in the vascular cylinder determines xylem cell types in a dosage-dependent manner.

  • 59.
    Castroviejo-Fisher, Santiago
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Population and Conservation Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    De la Riva, Ignacio
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Vilà, Carles
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Population and Conservation Biology.
    Transparent frogs show potential of natural world2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 449, no 7165, p. 972-972Article in journal (Refereed)
  • 60. Cederwall, B.
    et al.
    Moradi, F. Ghazi
    Back, T.
    Johnson, A.
    Blomqvist, J.
    Clement, E.
    de France, G.
    Wadsworth, R.
    Andgren, K.
    Lagergren, K.
    Dijon, A.
    Jaworski, G.
    Liotta, R.
    Qi, C.
    Nyako, B. M.
    Nyberg, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy. Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics.
    Palacz, M.
    Al-Azri, H.
    Algora, A.
    de Angelis, G.
    Atac, A.
    Bhattacharyya, S.
    Brock, T.
    Brown, J. R.
    Davies, P.
    Di Nitto, A.
    Dombradi, Zs.
    Gadea, A.
    Gal, J.
    Hadinia, B.
    Johnston-Theasby, F.
    Joshi, P.
    Juhasz, K.
    Julin, R.
    Jungclaus, A.
    Kalinka, G.
    Kara, S. O.
    Khaplanov, A.
    Kownacki, J.
    La Rana, G.
    Lenzi, S. M.
    Molnar, J.
    Moro, R.
    Napoli, D. R.
    Singh, B. S. Nara
    Persson, A.
    Recchia, F.
    Sandzelius, M.
    Scheurer, J. -N
    Sletten, G.
    Sohler, D.
    Söderström, Pär-Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Taylor, M. J.
    Timar, J.
    Valiente-Dobon, J. J.
    Vardaci, E.
    Williams, S.
    Evidence for a spin-aligned neutron-proton paired phase from the level structure of Pd-922011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 469, no 7328, p. 68-71Article in journal (Refereed)
    Abstract [en]

    Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work(1) that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing(2-6), in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus Pd-92. Gamma rays emitted following the Ni-58(Ar-36,2n)Pd-92 fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution c-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction(2-6). We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling(7,8)) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis.

  • 61.
    Chabera, Pavel
    et al.
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden..
    Liu, Yizhu
    Lund Univ, Dept Chem, CAS, Box 124, SE-22100 Lund, Sweden..
    Prakash, Om
    Lund Univ, Dept Chem, CAS, Box 124, SE-22100 Lund, Sweden..
    Thyrhaug, Erling
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden..
    El Nahhas, Amal
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden..
    Honarfar, Alireza
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden..
    Essen, Sofia
    Lund Univ, Dept Chem, CAS, Box 124, SE-22100 Lund, Sweden..
    Fredin, Lisa A.
    Lund Univ, Dept Chem, Div Theoret Chem, Box 124, SE-22100 Lund, Sweden..
    Harlang, Tobias C. B.
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden.;Tech Univ Denmark, Dept Phys, DK-2800 Lyngby, Denmark..
    Kjaer, Kasper S.
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden.;Tech Univ Denmark, Dept Phys, DK-2800 Lyngby, Denmark..
    Handrup, Karsten
    Lund Univ, Dept Phys, Div Synchrotron Radiat Res, Box 118, SE-22100 Lund, Sweden..
    Ericson, Fredric
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Tatsuno, Hideyuki
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden..
    Morgan, Kelsey
    NIST, Boulder, CO 80305 USA..
    Schnadt, Joachim
    Lund Univ, Dept Phys, Div Synchrotron Radiat Res, Box 118, SE-22100 Lund, Sweden..
    Häggström, Lennart
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Ericsson, Tore
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Sobkowiak, Adam
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Lidin, Sven
    Lund Univ, Dept Chem, CAS, Box 124, SE-22100 Lund, Sweden..
    Huang, Ping
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Styring, Stenbjörn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Uhlig, Jens
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden..
    Bendix, Jesper
    Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen, Denmark..
    Lomoth, Reiner
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Sundström, Villy
    Lund Univ, Dept Chem, Div Phys Chem, Box 124, SE-22100 Lund, Sweden..
    Persson, Petter
    Lund Univ, Dept Chem, Div Theoret Chem, Box 124, SE-22100 Lund, Sweden..
    Warnmark, Kenneth
    Lund Univ, Dept Chem, CAS, Box 124, SE-22100 Lund, Sweden..
    A low-spin Fe(III) complex with 100-ps ligand-to-metal charge transfer photoluminescence2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 543, no 7647, p. 695-+Article in journal (Refereed)
    Abstract [en]

    Transition-metal complexes are used as photosensitizers(1), in light-emitting diodes, for biosensing and in photocatalysis(2). A key feature in these applications is excitation from the ground state to a charge-transfer state(3,4); the long charge-transfer-state lifetimes typical for complexes of ruthenium(5) and other precious metals are often essential to ensure high performance. There is much interest in replacing these scarce elements with Earth-abundant metals, with iron(6) and copper(7) being particularly attractive owing to their low cost and non-toxicity. But despite the exploration of innovative molecular designs(6,8-10), it remains a formidable scientific challenge(11) to access Earth-abundant transition-metal complexes with long-lived charge-transfer excited states. No known iron complexes are considered(12) photoluminescent at room temperature, and their rapid excited-state deactivation precludes their use as photosensitizers(13-15). Here we present the iron complex [Fe(btz)(3)](3+) (where btz is 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene)), and show that the superior sigma-donor and pi-acceptor electron properties of the ligand stabilize the excited state sufficiently to realize a long charge-transfer lifetime of 100 picoseconds (ps) and room-temperature photoluminescence. This species is a low-spin Fe(III) d(5) complex, and emission occurs from a long-lived doublet ligand-to-metal charge-transfer ((LMCT)-L-2) state that is rarely seen for transition-metal complexes(4,16,17). The absence of intersystem crossing, which often gives rise to large excited-state energy losses in transition-metal complexes, enables the observation of spin-allowed emission directly to the ground state and could be exploited as an increased driving force in photochemical reactions on surfaces. These findings suggest that appropriate design strategies can deliver new iron-based materials for use as light emitters and photosensitizers.

  • 62. Chapman, Henry N.
    et al.
    Fromme, Petra
    Barty, Anton
    White, Thomas A.
    Kirian, Richard A.
    Aquila, Andrew
    Hunter, Mark S.
    Schulz, Joachim
    DePonte, Daniel P.
    Weierstall, Uwe
    Doak, R. Bruce
    Maia, Filipe R. N. C.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Martin, Andrew V.
    Schlichting, Ilme
    Lomb, Lukas
    Coppola, Nicola
    Shoeman, Robert L.
    Epp, Sascha W.
    Hartmann, Robert
    Rolles, Daniel
    Rudenko, Artem
    Foucar, Lutz
    Kimmel, Nils
    Weidenspointner, Georg
    Holl, Peter
    Liang, Mengning
    Barthelmess, Miriam
    Caleman, Carl
    Boutet, Sebastien
    Bogan, Michael J.
    Krzywinski, Jacek
    Bostedt, Christoph
    Bajt, Sasa
    Gumprecht, Lars
    Rudek, Benedikt
    Erk, Benjamin
    Schmidt, Carlo
    Hoemke, Andre
    Reich, Christian
    Pietschner, Daniel
    Strueder, Lothar
    Hauser, Guenter
    Gorke, Hubert
    Ullrich, Joachim
    Herrmann, Sven
    Schaller, Gerhard
    Schopper, Florian
    Soltau, Heike
    Kuehnel, Kai-Uwe
    Messerschmidt, Marc
    Bozek, John D.
    Hau-Riege, Stefan P.
    Frank, Matthias
    Hampton, Christina Y.
    Sierra, Raymond G.
    Starodub, Dmitri
    Williams, Garth J.
    Hajdu, Janos
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Timneanu, Nicusor
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Seibert, M. Marvin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Andreasson, Jakob
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Rocker, Andrea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Jönsson, Olof
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Svenda, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Stern, Stephan
    Nass, Karol
    Andritschke, Robert
    Schroeter, Claus-Dieter
    Krasniqi, Faton
    Bott, Mario
    Schmidt, Kevin E.
    Wang, Xiaoyu
    Grotjohann, Ingo
    Holton, James M.
    Barends, Thomas R. M.
    Neutze, Richard
    Marchesini, Stefano
    Fromme, Raimund
    Schorb, Sebastian
    Rupp, Daniela
    Adolph, Marcus
    Gorkhover, Tais
    Andersson, Inger
    SLU.
    Hirsemann, Helmut
    Potdevin, Guillaume
    Graafsma, Heinz
    Nilsson, Björn
    Spence, John C. H.
    Femtosecond X-ray protein nanocrystallography2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 470, no 7332, p. 73-77Article in journal (Refereed)
    Abstract [en]

    X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded(1-3). It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source(4). We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes(5). More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (similar to 200 nm to 2 mm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes(6). This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.

  • 63. Chapman, Henry N
    et al.
    Hau-Riege, Stefan P
    Bogan, Michael J
    Bajt, Sasa
    Barty, Anton
    Boutet, Sébastien
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Marchesini, Stefano
    Frank, Matthias
    Woods, Bruce W
    Benner, W Henry
    London, Richard A
    Rohner, Urs
    Szöke, Abraham
    Spiller, Eberhard
    Möller, Thomas
    Bostedt, Christoph
    Shapiro, David A
    Kuhlmann, Marion
    Treusch, Rolf
    Plönjes, Elke
    Burmeister, Florian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Bergh, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Caleman, Carl
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Huldt, Gösta
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Seibert, M. Marvin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Hajdu, Janos
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
    Femtosecond time-delay X-ray holography2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 448, no 7154, p. 676-679Article in journal (Refereed)
    Abstract [en]

    Extremely intense and ultrafast X-ray pulses from free-electron lasers offer unique opportunities to study fundamental aspects of complex transient phenomena in materials. Ultrafast time-resolved methods usually require highly synchronized pulses to initiate a transition and then probe it after a precisely defined time delay. In the X-ray regime, these methods are challenging because they require complex optical systems and diagnostics. Here we propose and apply a simple holographic measurement scheme, inspired by Newton's 'dusty mirror' experiment1, to monitor the X-ray-induced explosion of microscopic objects. The sample is placed near an X-ray mirror; after the pulse traverses the sample, triggering the reaction, it is reflected back onto the sample by the mirror to probe this reaction. The delay is encoded in the resulting diffraction pattern to an accuracy of one femtosecond, and the structural change is holographically recorded with high resolution. We apply the technique to monitor the dynamics of polystyrene spheres in intense free-electron-laser pulses, and observe an explosion occurring well after the initial pulse. Our results support the notion that X-ray flash imaging2, 3 can be used to achieve high resolution, beyond radiation damage limits for biological samples4. With upcoming ultrafast X-ray sources we will be able to explore the three-dimensional dynamics of materials at the timescale of atomic motion.

  • 64.
    Chapron, Guillaume
    et al.
    Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Epstein, Yaffa
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Law, Department of Law.
    López-Bao, José Vicente
    Oviedo University, Oviedo, Spain.
    Don’t let triage put a gloss on extinctions2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 554, no 7692, p. 300-300Article in journal (Refereed)
  • 65.
    Chen, Donglei
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Sanchez, Sophie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. European Synchrotron Radiat Facil, 6 Rue Jules Horowitz, F-38043 Grenoble, France..
    Tafforeau, Paul
    European Synchrotron Radiat Facil, 6 Rue Jules Horowitz, F-38043 Grenoble, France..
    Ahlberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The stem osteichthyan Andreolepis and the origin of tooth replacement2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 539, no 7628, p. 237-+Article in journal (Refereed)
    Abstract [en]

    The teeth of gnathostomes (jawed vertebrates) show rigidly patterned, unidirectional replacement that may or may not be associated with a shedding mechanism. These mechanisms, which are critical for the maintenance of the dentition, are incongruently distributed among extant gnathostomes. Although a permanent tooth-generating dental lamina is present in all chondrichthyans, many tetrapods and some teleosts, it is absent in the non-teleost actinopterygians. Tooth-shedding by basal hard tissue resorption occurs in most osteichthyans (including tetrapods) but not in chondrichthyans. Here we report a three-dimensional virtual dissection of the dentition of a 424-million-year-old stem osteichthyan, Andreolepis hedei, using propagation phase-contrast synchrotron microtomography, with a reconstruction of its growth history. Andreolepis, close to the common ancestor of all extant osteichthyans, shed its teeth by basal resorption but probably lacked a permanent dental lamina. This is the earliest documented instance of resorptive tooth shedding and may represent the primitive osteichthyan mode of tooth replacement.

  • 66. Chen, Richard Z
    et al.
    Pettersson, Ulf
    Whitehead Institute for Biomedical Research, Department of Biology, Cambridge, USA.
    Beard, Caroline
    Jackson-Grusby, Laurie
    Jaenisch, Rudolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Medical Genetics.
    DNA hypomethylation leads to elevated mutation rates1998In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 395, no 6697, p. 89-93Article in journal (Refereed)
    Abstract [en]

    Genome-wide demethylation has been suggested to be a step in carcinogenesis. Evidence for this notion comes from the frequently observed global DNA hypomethylation in tumour cells, and from a recent study suggesting that defects in DNA methylation might contribute to the genomic instability of some colorectal tumour cell lines. DNA hypomethylation has also been associated with abnormal chromosomal structures, as observed in cells from patients with ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome and in cells treated with the demethylating agent 5-azadeoxycytidine. Here we report that murine embryonic stem cells nullizygous for the major DNA methyltransferase (Dnmt1) gene exhibited significantly elevated mutation rates at both the endogenous hypoxanthine phosphoribosyltransferase (Hprt) gene and an integrated viral thymidine kinase (tk) transgene. Gene deletions were the predominant mutations at both loci. The major cause of the observed tk deletions was either mitotic recombination or chromosomal loss accompanied by duplication of the remaining chromosome. Our results imply an important role for mammalian DNA methylation in maintaining genome stability.

  • 67. Clack, J. A.
    et al.
    Ahlberg, Per E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Finney, S. M.
    Dominguez Alonso, P.
    Robinson, J.
    Ketcham, R. A.
    A uniquely specialized ear in a very early tetrapod2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 425, no 6953, p. 66-69Article in journal (Refereed)
  • 68. Clark, Andrew G.
    et al.
    Eisen, Michael B.
    Smith, Douglas R.
    Bergman, Casey M.
    Oliver, Brian
    Markow, Therese A.
    Kaufman, Thomas C.
    Kellis, Manolis
    Gelbart, William
    Iyer, Venky N.
    Pollard, Daniel A.
    Sackton, Timothy B.
    Larracuente, Amanda M.
    Singh, Nadia D.
    Abad, Jose P.
    Abt, Dawn N.
    Adryan, Boris
    Aguade, Montserrat
    Akashi, Hiroshi
    Anderson, Wyatt W.
    Aquadro, Charles F.
    Ardell, David H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Arguello, Roman
    Artieri, Carlo G.
    Barbash, Daniel A.
    Barker, Daniel
    Barsanti, Paolo
    Batterham, Phil
    Batzoglou, Serafim
    Begun, Dave
    Bhutkar, Arjun
    Blanco, Enrico
    Bosak, Stephanie A.
    Bradley, Robert K.
    Brand, Adrianne D.
    Brent, Michael R.
    Brooks, Angela N.
    Brown, Randall H.
    Butlin, Roger K.
    Caggese, Corrado
    Calvi, Brian R.
    de Carvalho, A. Bernardo
    Caspi, Anat
    Castrezana, Sergio
    Celniker, Susan E.
    Chang, Jean L.
    Chapple, Charles
    Chatterji, Sourav
    Chinwalla, Asif
    Civetta, Alberto
    Clifton, Sandra W.
    Comeron, Josep M.
    Costello, James C.
    Coyne, Jerry A.
    Daub, Jennifer
    David, Robert G.
    Delcher, Arthur L.
    Delehaunty, Kim
    Do, Chuong B.
    Ebling, Heather
    Edwards, Kevin
    Eickbush, Thomas
    Evans, Jay D.
    Filipski, Alan
    Findeiss, Sven
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Fulton, Lucinda
    Fulton, Robert
    Garcia, Ana C. L.
    Gardiner, Anastasia
    Garfield, David A.
    Garvin, Barry E.
    Gibson, Greg
    Gilbert, Don
    Gnerre, Sante
    Godfrey, Jennifer
    Good, Robert
    Gotea, Valer
    Gravely, Brenton
    Greenberg, Anthony J.
    Griffiths-Jones, Sam
    Gross, Samuel
    Guigo, Roderic
    Gustafson, Erik A.
    Haerty, Wilfried
    Hahn, Matthew W.
    Halligan, Daniel L.
    Halpern, Aaron L.
    Halter, Gillian M.
    Han, Mira V.
    Heger, Andreas
    Hillier, LaDeana
    Hinrichs, Angie S.
    Holmes, Ian
    Hoskins, Roger A.
    Hubisz, Melissa J.
    Hultmark, Dan
    Huntley, Melanie A.
    Jaffe, David B.
    Jagadeeshan, Santosh
    Jeck, William R.
    Johnson, Justin
    Jones, Corbin D.
    Jordan, William C.
    Karpen, Gary H.
    Kataoka, Eiko
    Keightley, Peter D.
    Kheradpour, Pouya
    Kirkness, Ewen F.
    Koerich, Leonardo B.
    Kristiansen, Karsten
    Kudrna, Dave
    Kulathinal, Rob J.
    Kumar, Sudhir
    Kwok, Roberta
    Lander, Eric
    Langley, Charles H.
    Lapoint, Richard
    Lazzaro, Brian P.
    Lee, So-Jeong
    Levesque, Lisa
    Li, Ruiqiang
    Lin, Chiao-Feng
    Lin, Michael F.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Llopart, Ana
    Long, Manyuan
    Low, Lloyd
    Lozovsky, Elena
    Lu, Jian
    Luo, Meizhong
    Machado, Carlos A.
    Makalowski, Wojciech
    Marzo, Mar
    Matsuda, Muneo
    Matzkin, Luciano
    McAllister, Bryant
    McBride, Carolyn S.
    McKernan, Brendan
    McKernan, Kevin
    Mendez-Lago, Maria
    Minx, Patrick
    Mollenhauer, Michael U.
    Montooth, Kristi
    Mount, Stephen M.
    Mu, Xu
    Myers, Eugene
    Negre, Barbara
    Newfeld, Stuart
    Nielsen, Rasmus
    Noor, Mohamed A. F.
    O'Grady, Patrick
    Pachter, Lior
    Papaceit, Montserrat
    Parisi, Matthew J.
    Parisi, Michael
    Parts, Leopold
    Pedersen, Jakob S.
    Pesole, Graziano
    Phillippy, Adam M.
    Ponting, Chris P.
    Pop, Mihai
    Porcelli, Damiano
    Powell, Jeffrey R.
    Prohaska, Sonja
    Pruitt, Kim
    Puig, Marta
    Quesneville, Hadi
    Ram, Kristipati Ravi
    Rand, David
    Rasmussen, Matthew D.
    Reed, Laura K.
    Reenan, Robert
    Reily, Amy
    Remington, Karin A.
    Rieger, Tania T.
    Ritchie, Michael G.
    Robin, Charles
    Rogers, Yu-Hui
    Rohde, Claudia
    Rozas, Julio
    Rubenfield, Marc J.
    Ruiz, Alfredo
    Russo, Susan
    Salzberg, Steven L.
    Sanchez-Gracia, Alejandro
    Saranga, David J.
    Sato, Hajime
    Schaeffer, Stephen W.
    Schatz, Michael C.
    Schlenke, Todd
    Schwartz, Russell
    Segarra, Carmen
    Singh, Rama S.
    Sirot, Laura
    Sirota, Marina
    Sisneros, Nicholas B.
    Smith, Chris D.
    Smith, Temple F.
    Spieth, John
    Stage, Deborah E.
    Stark, Alexander
    Stephan, Wolfgang
    Strausberg, Robert L.
    Strempel, Sebastian
    Sturgill, David
    Sutton, Granger
    Sutton, Granger G.
    Tao, Wei
    Teichmann, Sarah
    Tobari, Yoshiko N.
    Tomimura, Yoshihiko
    Tsolas, Jason M.
    Valente, Vera L. S.
    Venter, Eli
    Venter, J. Craig
    Vicario, Saverio
    Vieira, Filipe G.
    Vilella, Albert J.
    Villasante, Alfredo
    Walenz, Brian
    Wang, Jun
    Wasserman, Marvin
    Watts, Thomas
    Wilson, Derek
    Wilson, Richard K.
    Wing, Rod A.
    Wolfner, Mariana F.
    Wong, Alex
    Wong, Gane Ka-Shu
    Wu, Chung-I
    Wu, Gabriel
    Yamamoto, Daisuke
    Yang, Hsiao-Pei
    Yang, Shiaw-Pyng
    Yorke, James A.
    Yoshida, Kiyohito
    Zdobnov, Evgeny
    Zhang, Peili
    Zhang, Yu
    Zimin, Aleksey V.
    Baldwin, Jennifer
    Abdouelleil, Amr
    Abdulkadir, Jamal
    Abebe, Adal
    Abera, Brikti
    Abreu, Justin
    Acer, St Christophe
    Aftuck, Lynne
    Alexander, Allen
    An, Peter
    Anderson, Erica
    Anderson, Scott
    Arachi, Harindra
    Azer, Marc
    Bachantsang, Pasang
    Barry, Andrew
    Bayul, Tashi
    Berlin, Aaron
    Bessette, Daniel
    Bloom, Toby
    Blye, Jason
    Boguslavskiy, Leonid
    Bonnet, Claude
    Boukhgalter, Boris
    Bourzgui, Imane
    Brown, Adam
    Cahill, Patrick
    Channer, Sheridon
    Cheshatsang, Yama
    Chuda, Lisa
    Citroen, Mieke
    Collymore, Alville
    Cooke, Patrick
    Costello, Maura
    D'Aco, Katie
    Daza, Riza
    De Haan, Georgius
    DeGray, Stuart
    DeMaso, Christina
    Dhargay, Norbu
    Dooley, Kimberly
    Dooley, Erin
    Doricent, Missole
    Dorje, Passang
    Dorjee, Kunsang
    Dupes, Alan
    Elong, Richard
    Falk, Jill
    Farina, Abderrahim
    Faro, Susan
    Ferguson, Diallo
    Fisher, Sheila
    Foley, Chelsea D.
    Franke, Alicia
    Friedrich, Dennis
    Gadbois, Loryn
    Gearin, Gary
    Gearin, Christina R.
    Giannoukos, Georgia
    Goode, Tina
    Graham, Joseph
    Grandbois, Edward
    Grewal, Sharleen
    Gyaltsen, Kunsang
    Hafez, Nabil
    Hagos, Birhane
    Hall, Jennifer
    Henson, Charlotte
    Hollinger, Andrew
    Honan, Tracey
    Huard, Monika D.
    Hughes, Leanne
    Hurhula, Brian
    Husby, M. Erii
    Kamat, Asha
    Kanga, Ben
    Kashin, Seva
    Khazanovich, Dmitry
    Kisner, Peter
    Lance, Krista
    Lara, Marcia
    Lee, William
    Lennon, Niall
    Letendre, Frances
    LeVine, Rosie
    Lipovsky, Alex
    Liu, Xiaohong
    Liu, Jinlei
    Liu, Shangtao
    Lokyitsang, Tashi
    Lokyitsang, Yeshi
    Lubonja, Rakela
    Lui, Annie
    MacDonald, Pen
    Magnisalis, Vasilia
    Maru, Kebede
    Matthews, Charles
    McCusker, William
    McDonough, Susan
    Mehta, Teena
    Meldrim, James
    Meneus, Louis
    Mihai, Oana
    Mihalev, Atanas
    Mihova, Tanya
    Mittelman, Rachel
    Mlenga, Valentine
    Montmayeur, Anna
    Mulrain, Leonidas
    Navidi, Adam
    Naylor, Jerome
    Negash, Tamrat
    Nguyen, Thu
    Nguyen, Nga
    Nicol, Robert
    Norbu, Choe
    Norbu, Nyima
    Novod, Nathaniel
    O'Neill, Barry
    Osman, Sahal
    Markiewicz, Eva
    Oyono, Otero L.
    Patti, Christopher
    Phunkhang, Pema
    Pierre, Fritz
    Priest, Margaret
    Raghuraman, Sujaa
    Rege, Filip
    Reyes, Rebecca
    Rise, Cecil
    Rogov, Peter
    Ross, Keenan
    Ryan, Elizabeth
    Settipalli, Sampath
    Shea, Terry
    Sherpa, Ngawang
    Shi, Lu
    Shih, Diana
    Sparrow, Todd
    Spaulding, Jessica
    Stalker, John
    Stange-Thomann, Nicole
    Stavropoulos, Sharon
    Stone, Catherine
    Strader, Christopher
    Tesfaye, Senait
    Thomson, Talene
    Thoulutsang, Yama
    Thoulutsang, Dawa
    Topham, Kerri
    Topping, Ira
    Tsamla, Tsamla
    Vassiliev, Helen
    Vo, Andy
    Wangchuk, Tsering
    Wangdi, Tsering
    Weiand, Michael
    Wilkinson, Jane
    Wilson, Adam
    Yadav, Shailendra
    Young, Geneva
    Yu, Qing
    Zembek, Lisa
    Zhong, Danni
    Zimmer, Andrew
    Zwirko, Zac
    Alvarez, Pablo
    Brockman, Will
    Butler, Jonathan
    Chin, CheeWhye
    Grabherr, Manfred
    Kleber, Michael
    Mauceli, Evan
    MacCallum, Iain
    Evolution of genes and genomes on the Drosophila phylogeny.2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 450, no 7167, p. 203-218Article in journal (Refereed)
    Abstract [en]

    Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

  • 69. Clutton-Brock, T. H.
    et al.
    Hodge, S. J.
    Spong, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Animal Ecology.
    Russell, A. F.
    Jordan, N. R.
    Bennett, N. C.
    Sharpe, L. L.
    Manser, M. B.
    Intrasexual competition and sexual selection in cooperative mammals2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 444, no 7122, p. 1065-1068Article in journal (Refereed)
    Abstract [en]

    In most animals, the sex that invests least in its offspring competes more intensely for access to the opposite sex and shows greater development of secondary sexual characters than the sex that invests most(1,2). However, in some mammals where females are the primary care-givers, females compete more frequently or intensely with each other than males(3-5). A possible explanation is that, in these species, the resources necessary for successful female reproduction are heavily concentrated and intrasexual competition for breeding opportunities is more intense among females than among males. Intrasexual competition between females is likely to be particularly intense in cooperative breeders where a single female monopolizes reproduction in each group(6). Here, we use data from a twelve-year study of wild meerkats (Suricata suricatta), where females show high levels of reproductive skew, to show that females gain greater benefits from acquiring dominant status than males and traits that increase competitive ability exert a stronger influence on their breeding success. Females that acquire dominant status also develop a suite of morphological, physiological and behavioural characteristics that help them to control other group members. Our results show that sex differences in parental investment are not the only mechanism capable of generating sex differences in reproductive competition and emphasize the extent to which competition for breeding opportunities between females can affect the evolution of sex differences and the operation of sexual selection.

  • 70. Conrad, Donald F.
    et al.
    Pinto, Dalila
    Redon, Richard
    Feuk, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gokcumen, Omer
    Zhang, Yujun
    Aerts, Jan
    Andrews, T. Daniel
    Barnes, Chris
    Campbell, Peter
    Fitzgerald, Tomas
    Hu, Min
    Ihm, Chun Hwa
    Kristiansson, Kati
    MacArthur, Daniel G.
    MacDonald, Jeffrey R.
    Onyiah, Ifejinelo
    Pang, Andy Wing Chun
    Robson, Sam
    Stirrups, Kathy
    Valsesia, Armand
    Walter, Klaudia
    Wei, John
    Tyler-Smith, Chris
    Carter, Nigel P.
    Lee, Charles
    Scherer, Stephen W.
    Hurles, Matthew E.
    Origins and functional impact of copy number variation in the human genome2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7289, p. 704-712Article in journal (Refereed)
    Abstract [en]

    Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.

  • 71. Constância, Miguel
    et al.
    Hemberger, Myriam
    Hughes, Jennifer
    Dean, Wendy
    Ferguson-Smith, Anne
    Fundele, Reinald
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Stewart, Francesca
    Kelsey, Gavin
    Fowden, Abigail
    Sibley, Colin
    Reik, Wolf
    Placental-specific IGF-II is a major modulator of placental and fetal growth2002In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 417, no 6892, p. 945-8Article in journal (Refereed)
  • 72. Craddock, Nick
    et al.
    Hurles, Matthew E.
    Cardin, Niall
    Pearson, Richard D.
    Plagnol, Vincent
    Robson, Samuel
    Vukcevic, Damjan
    Barnes, Chris
    Conrad, Donald F.
    Giannoulatou, Eleni
    Holmes, Chris
    Marchini, Jonathan L.
    Stirrups, Kathy
    Tobin, Martin D.
    Wain, Louise V.
    Yau, Chris
    Aerts, Jan
    Ahmad, Tariq
    Andrews, T. Daniel
    Arbury, Hazel
    Attwood, Anthony
    Auton, Adam
    Ball, Stephen G.
    Balmforth, Anthony J.
    Barrett, Jeffrey C.
    Barroso, Ines
    Barton, Anne
    Bennett, Amanda J.
    Bhaskar, Sanjeev
    Blaszczyk, Katarzyna
    Bowes, John
    Brand, Oliver J.
    Braund, Peter S.
    Bredin, Francesca
    Breen, Gerome
    Brown, Morris J.
    Bruce, Ian N.
    Bull, Jaswinder
    Burren, Oliver S.
    Burton, John
    Byrnes, Jake
    Caesar, Sian
    Clee, Chris M.
    Coffey, Alison J.
    Connell, John M. C.
    Cooper, Jason D.
    Dominiczak, Anna F.
    Downes, Kate
    Drummond, Hazel E.
    Dudakia, Darshna
    Dunham, Andrew
    Ebbs, Bernadette
    Eccles, Diana
    Edkins, Sarah
    Edwards, Cathryn
    Elliot, Anna
    Emery, Paul
    Evans, David M.
    Evans, Gareth
    Eyre, Steve
    Farmer, Anne
    Ferrier, I. Nicol
    Feuk, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Fitzgerald, Tomas
    Flynn, Edward
    Forbes, Alistair
    Forty, Liz
    Franklyn, Jayne A.
    Freathy, Rachel M.
    Gibbs, Polly
    Gilbert, Paul
    Gokumen, Omer
    Gordon-Smith, Katherine
    Gray, Emma
    Green, Elaine
    Groves, Chris J.
    Grozeva, Detelina
    Gwilliam, Rhian
    Hall, Anita
    Hammond, Naomi
    Hardy, Matt
    Harrison, Pile
    Hassanali, Neelam
    Hebaishi, Husam
    Hines, Sarah
    Hinks, Anne
    Hitman, Graham A.
    Hocking, Lynne
    Howard, Eleanor
    Howard, Philip
    Howson, Joanna M. M.
    Hughes, Debbie
    Hunt, Sarah
    Isaacs, John D.
    Jain, Mahim
    Jewell, Derek P.
    Johnson, Toby
    Jolley, Jennifer D.
    Jones, Ian R.
    Jones, Lisa A.
    Kirov, George
    Langford, Cordelia F.
    Lango-Allen, Hana
    Lathrop, G. Mark
    Lee, James
    Lee, Kate L.
    Lees, Charlie
    Lewis, Kevin
    Lindgren, Cecilia M.
    Maisuria-Armer, Meeta
    Maller, Julian
    Mansfield, John
    Martin, Paul
    Massey, Dunecan C. O.
    McArdle, Wendy L.
    McGuffin, Peter
    McLay, Kirsten E.
    Mentzer, Alex
    Mimmack, Michael L.
    Morgan, Ann E.
    Morris, Andrew P.
    Mowat, Craig
    Myers, Simon
    Newman, William
    Nimmo, Elaine R.
    O'Donovan, Michael C.
    Onipinla, Abiodun
    Onyiah, Ifejinelo
    Ovington, Nigel R.
    Owen, Michael J.
    Palin, Kimmo
    Parnell, Kirstie
    Pernet, David
    Perry, John R. B.
    Phillips, Anne
    Pinto, Dalila
    Prescott, Natalie J.
    Prokopenko, Inga
    Quail, Michael A.
    Rafelt, Suzanne
    Rayner, Nigel W.
    Redon, Richard
    Reid, David M.
    Renwick, Anthony
    Ring, Susan M.
    Robertson, Neil
    Russell, Ellie
    St Clair, David
    Sambrook, Jennifer G.
    Sanderson, Jeremy D.
    Schuilenburg, Helen
    Scott, Carol E.
    Scott, Richard
    Seal, Sheila
    Shaw-Hawkins, Sue
    Shields, Beverley M.
    Simmonds, Matthew J.
    Smyth, Debbie J.
    Somaskantharajah, Elilan
    Spanova, Katarina
    Steer, Sophia
    Stephens, Jonathan
    Stevens, Helen E.
    Stone, Millicent A.
    Su, Zhan
    Symmons, Deborah P. M.
    Thompson, John R.
    Thomson, Wendy
    Travers, Mary E.
    Turnbull, Clare
    Valsesia, Armand
    Walker, Mark
    Walker, Neil M.
    Wallace, Chris
    Warren-Perry, Margaret
    Watkins, Nicholas A.
    Webster, John
    Weedon, Michael N.
    Wilson, Anthony G.
    Woodburn, Matthew
    Wordsworth, B. Paul
    Young, Allan H.
    Zeggini, Eleftheria
    Carter, Nigel P.
    Frayling, Timothy M.
    Lee, Charles
    McVean, Gil
    Munroe, Patricia B.
    Palotie, Aarno
    Sawcer, Stephen J.
    Scherer, Stephen W.
    Strachan, David P.
    Tyler-Smith, Chris
    Brown, Matthew A.
    Burton, Paul R.
    Caulfield, Mark J.
    Compston, Alastair
    Farrall, Martin
    Gough, Stephen C. L.
    Hall, Alistair S.
    Hattersley, Andrew T.
    Hill, Adrian V. S.
    Mathew, Christopher G.
    Pembrey, Marcus
    Satsangi, Jack
    Stratton, Michael R.
    Worthington, Jane
    Deloukas, Panos
    Duncanson, Audrey
    Kwiatkowski, Dominic P.
    McCarthy, Mark I.
    Ouwehand, Willem H.
    Parkes, Miles
    Rahman, Nazneen
    Todd, John A.
    Samani, Nilesh J.
    Donnelly, Peter
    Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7289, p. 713-720Article in journal (Refereed)
    Abstract [en]

    Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

  • 73. Curtis, Bruce A.
    et al.
    Tanifuji, Goro
    Burki, Fabien
    Gruber, Ansgar
    Irimia, Manuel
    Maruyama, Shinichiro
    Arias, Maria C.
    Ball, Steven G.
    Gile, Gillian H.
    Hirakawa, Yoshihisa
    Hopkins, Julia F.
    Kuo, Alan
    Rensing, Stefan A.
    Schmutz, Jeremy
    Symeonidi, Aikaterini
    Elias, Marek
    Eveleigh, Robert J. M.
    Herman, Emily K.
    Klute, Mary J.
    Nakayama, Takuro
    Obornik, Miroslav
    Reyes-Prieto, Adrian
    Armbrust, E. Virginia
    Aves, Stephen J.
    Beiko, Robert G.
    Coutinho, Pedro
    Dacks, Joel B.
    Durnford, Dion G.
    Fast, Naomi M.
    Green, Beverley R.
    Grisdale, Cameron J.
    Hempel, Franziska
    Henrissat, Bernard
    Höppner, Marc P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ishida, Ken-Ichiro
    Kim, Eunsoo
    Koreny, Lude. K.
    Kroth, Peter G.
    Liu, Yuan
    Malik, Shehre-Banoo
    Maier, Uwe G.
    McRose, Darcy
    Mock, Thomas
    Neilson, Jonathan A. D.
    Onodera, Naoko T.
    Poole, Anthony M.
    Pritham, Ellen J.
    Richards, Thomas A.
    Rocap, Gabrielle
    Roy, Scott W.
    Sarai, Chihiro
    Schaack, Sarah
    Shirato, Shu
    Slamovits, Claudio H.
    Spencer, David F.
    Suzuki, Shigekatsu
    Worden, Alexandra Z.
    Zauner, Stefan
    Barry, Kerrie
    Bell, Callum
    Bharti, Arvind K.
    Crow, John A.
    Grimwood, Jane
    Kramer, Robin
    Lindquist, Erika
    Lucas, Susan
    Salamov, Asaf
    McFadden, Geoffrey I.
    Lane, Christopher E.
    Keeling, Patrick J.
    Gray, Michael W.
    Grigoriev, Igor V.
    Archibald, John M.
    Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 492, no 7427, p. 59-65Article in journal (Refereed)
    Abstract [en]

    Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host-and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.

  • 74. Dahl-Jensen, D.
    et al.
    Albert, M. R.
    Aldahan, Ala
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, LUVAL.
    Azuma, N.
    Balslev-Clausen, D.
    Baumgartner, M.
    Berggren, Ann-Marie
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Bigler, M.
    Binder, T.
    Blunier, T.
    Bourgeois, J. C.
    Brook, E. J.
    Buchardt, S. L.
    Buizert, C.
    Capron, E.
    Chappellaz, J.
    Chung, J.
    Clausen, H. B.
    Cvijanovic, I.
    Davies, S. M.
    Ditlevsen, P.
    Eicher, O.
    Fischer, H.
    Fisher, D. A.
    Fleet, L. G.
    Gfeller, G.
    Gkinis, V.
    Gogineni, S.
    Goto-Azuma, K.
    Grinsted, A.
    Gudlaugsdottir, H.
    Guillevic, M.
    Hansen, S. B.
    Hansson, M.
    Hirabayashi, M.
    Hong, S.
    Hur, S. D.
    Huybrechts, P.
    Hvidberg, C. S.
    Iizuka, Y.
    Jenk, T.
    Johnsen, S. J.
    Jones, T. R.
    Jouzel, J.
    Karlsson, N. B.
    Kawamura, K.
    Keegan, K.
    Kettner, E.
    Kipfstuhl, S.
    Kjaer, H. A.
    Koutnik, M.
    Kuramoto, T.
    Koehler, P.
    Laepple, T.
    Landais, A.
    Langen, P. L.
    Larsen, L. B.
    Leuenberger, D.
    Leuenberger, M.
    Leuschen, C.
    Li, J.
    Lipenkov, V.
    Martinerie, P.
    Maselli, O. J.
    Masson-Delmotte, V.
    McConnell, J. R.
    Miller, H.
    Mini, O.
    Miyamoto, A.
    Montagnat-Rentier, M.
    Mulvaney, R.
    Muscheler, R.
    Orsi, A. J.
    Paden, J.
    Panton, C.
    Pattyn, F.
    Petit, J. -R
    Pol, K.
    Popp, T.
    Possnert, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, För teknisk-naturvetenskapliga fakulteten gemensamma enheter, Tandem Laboratory.
    Prie, F.
    Prokopiou, M.
    Quiquet, A.
    Rasmussen, S. O.
    Raynaud, D.
    Ren, J.
    Reutenauer, C.
    Ritz, C.
    Rockmann, T.
    Rosen, J. L.
    Rubino, M.
    Rybak, O.
    Samyn, D.
    Sapart, C. J.
    Schilt, A.
    Schmidt, A. M. Z.
    Schwander, J.
    Schuepbach, S.
    Seierstad, I.
    Severinghaus, J. P.
    Sheldon, S.
    Simonsen, S. B.
    Sjolte, J.
    Solgaard, A. M.
    Sowers, T.
    Sperlich, P.
    Steen-Larsen, H. C.
    Steffen, K.
    Steffensen, J. P.
    Steinhage, D.
    Stocker, T. F.
    Stowasser, C.
    Sturevik, A. S.
    Sturges, W. T.
    Sveinbjornsdottir, A.
    Svensson, A.
    Tison, J. -L
    Uetake, J.
    Vallelonga, P.
    van de Wal, R. S. W.
    van der Wel, G.
    Vaughn, B. H.
    Vinther, B.
    Waddington, E.
    Wegner, A.
    Weikusat, I.
    White, J. W. C.
    Wilhelms, F.
    Winstrup, M.
    Witrant, E.
    Wolff, E. W.
    Xiao, C.
    Zheng, J.
    Eemian interglacial reconstructed from a Greenland folded ice core2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 493, no 7433, p. 489-494Article in journal (Refereed)
    Abstract [en]

    Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.

  • 75.
    de Goffau, Marcus C.
    et al.
    Wellcome Sanger Inst, Cambridge, England;Univ Cambridge, Dept Vet Med, Cambridge, England.
    Lager, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research. Univ Cambridge, Natl Inst Hlth Res Biomed Res Ctr, Dept Obstet & Gynaecol, Cambridge, England;Univ Cambridge, Dept Physiol Dev & Neurosci, CTR, Cambridge, England.
    Sovio, Ulla
    Univ Cambridge, Natl Inst Hlth Res Biomed Res Ctr, Dept Obstet & Gynaecol, Cambridge, England;Univ Cambridge, Dept Physiol Dev & Neurosci, CTR, Cambridge, England.
    Gaccioli, Francesca
    Univ Cambridge, Natl Inst Hlth Res Biomed Res Ctr, Dept Obstet & Gynaecol, Cambridge, England;Univ Cambridge, Dept Physiol Dev & Neurosci, CTR, Cambridge, England.
    Cook, Emma
    Univ Cambridge, Natl Inst Hlth Res Biomed Res Ctr, Dept Obstet & Gynaecol, Cambridge, England.
    Peacock, Sharon J.
    Wellcome Sanger Inst, Cambridge, England;Univ Cambridge, Dept Med, Cambridge, England;London Sch Hyg & Trop Med, London, England.
    Parkhill, Julian
    Wellcome Sanger Inst, Cambridge, England;Univ Cambridge, Dept Vet Med, Cambridge, England.
    Charnock-Jones, D. Stephen
    Univ Cambridge, Natl Inst Hlth Res Biomed Res Ctr, Dept Obstet & Gynaecol, Cambridge, England;Univ Cambridge, Dept Physiol Dev & Neurosci, CTR, Cambridge, England.
    Smith, Gordon C. S.
    Univ Cambridge, Natl Inst Hlth Res Biomed Res Ctr, Dept Obstet & Gynaecol, Cambridge, England;Univ Cambridge, Dept Physiol Dev & Neurosci, CTR, Cambridge, England.
    Human placenta has no microbiome but can contain potential pathogens2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 572, no 7769, p. 329-334Article in journal (Refereed)
    Abstract [en]

    We sought to determine whether pre-eclampsia, spontaneous preterm birth or the delivery of infants who are small for gestational age were associated with the presence of bacterial DNA in the human placenta. Here we show that there was no evidence for the presence of bacteria in the large majority of placental samples, from both complicated and uncomplicated pregnancies. Almost all signals were related either to the acquisition of bacteria during labour and delivery, or to contamination of laboratory reagents with bacterial DNA. The exception was Streptococcus agalactiae (group B Streptococcus), for which non-contaminant signals were detected in approximately 5% of samples collected before the onset of labour. We conclude that bacterial infection of the placenta is not a common cause of adverse pregnancy outcome and that the human placenta does not have a microbiome, but it does represent a potential site of perinatal acquisition of S. agalactiae, a major cause of neonatal sepsis.

  • 76.
    Deodhar, Ganesh Bhaskar
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy, Mathematics and Science Section.
    Fine structure of K-absorption limit of silicon oxide1930In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 125, p. 777-778Article in journal (Refereed)
    Abstract [en]

    THAT the X-ray absorption limits are not simple but show a rather complicated structure has been known now for some time. The main difficulties in their experimental investigation are in respect of (1) amount of the absorbing substance, and (2) dispersion of the spectrograph. The amount of the absorber must not be either too great or too small, otherwise the details are lost. Secondly, the dispersion must be made as large as possible to bring out all the details and measure them with the usual accuracy.

  • 77. Ding, Li
    et al.
    Getz, Gad
    Wheeler, David A
    Mardis, Elaine R
    McLellan, Michael D
    Cibulskis, Kristian
    Sougnez, Carrie
    Greulich, Heidi
    Muzny, Donna M
    Morgan, Margaret B
    Fulton, Lucinda
    Fulton, Robert S
    Zhang, Qunyuan
    Wendl, Michael C
    Lawrence, Michael S
    Larson, David E
    Chen, Ken
    Dooling, David J
    Sabo, Aniko
    Hawes, Alicia C
    Shen, Hua
    Jhangiani, Shalini N
    Lewis, Lora R
    Hall, Otis
    Zhu, Yiming
    Mathew, Tittu
    Ren, Yanru
    Yao, Jiqiang
    Scherer, Steven E
    Clerc, Kerstin
    Metcalf, Ginger A
    Ng, Brian
    Milosavljevic, Aleksandar
    Gonzalez-Garay, Manuel L
    Osborne, John R
    Meyer, Rick
    Shi, Xiaoqi
    Tang, Yuzhu
    Koboldt, Daniel C
    Lin, Ling
    Abbott, Rachel
    Miner, Tracie L
    Pohl, Craig
    Fewell, Ginger
    Haipek, Carrie
    Schmidt, Heather
    Dunford-Shore, Brian H
    Kraja, Aldi
    Crosby, Seth D
    Sawyer, Christopher S
    Vickery, Tammi
    Sander, Sacha
    Robinson, Jody
    Winckler, Wendy
    Baldwin, Jennifer
    Chirieac, Lucian R
    Dutt, Amit
    Fennell, Tim
    Hanna, Megan
    Johnson, Bruce E
    Onofrio, Robert C
    Thomas, Roman K
    Tonon, Giovanni
    Weir, Barbara A
    Zhao, Xiaojun
    Ziaugra, Liuda
    Zody, Michael C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Giordano, Thomas
    Orringer, Mark B
    Roth, Jack A
    Spitz, Margaret R
    Wistuba, Ignacio I
    Ozenberger, Bradley
    Good, Peter J
    Chang, Andrew C
    Beer, David G
    Watson, Mark A
    Ladanyi, Marc
    Broderick, Stephen
    Yoshizawa, Akihiko
    Travis, William D
    Pao, William
    Province, Michael A
    Weinstock, George M
    Varmus, Harold E
    Gabriel, Stacey B
    Lander, Eric S
    Gibbs, Richard A
    Meyerson, Matthew
    Wilson, Richard K
    Somatic mutations affect key pathways in lung adenocarcinoma2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 455, no 7216, p. 1069-1075Article in journal (Refereed)
    Abstract [en]

    Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.

  • 78.
    Dupret, Vincent
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Sanchez, Sophie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Goujet, Daniel
    Tafforeau, Paul
    Ahlberg, Per Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    A primitive placoderm sheds light on the origin of the jawed vertebrate face2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 507, no 7493, p. 500-503Article in journal (Refereed)
    Abstract [en]

    Extant vertebrates form two clades, the jawless Cyclostomata (lampreys and hagfishes) and the jawed Gnathostomata (all other vertebrates), with contrasting facial architectures(1,2). These arise during development from just a few key differences in the growth patterns of the cranial primordia: notably, the nasal sacs and hypophysis originate from a single placode in cyclostomes but from separate placodes in gnathostomes, and infraoptic ectomesenchyme migrates forward either side of the single placode in cyclostomes but between the placodes in gnathostomes(3-8). Fossil stem gnathostomes preserve cranial anatomies rich in landmarks that provide proxies for developmental processes and allow the transition from jawless to jawed vertebrates to be broken down into evolutionary steps(7,9-12). Here we use propagation phase contrast synchrotron microtomography to image the cranial anatomy of the primitive placoderm (jawed stem gnathostome) Romundina(13), and show that itcombines jawed vertebrate architecture with cranial and cerebral proportions resembling those of cyclostomes and the galeaspid (jawless stem gnathostome) Shuyu(11). This combination seems to be primitive for jawed vertebrates, and suggests a decoupling between ectomesenchymal growth trajectory, ectomesenchymal proliferation, and cerebral shape change during the origin of gnathostomes.

  • 79. Eghbali, M
    et al.
    Curmi, J P
    Birnir, Bryndis
    John Curtin School of Medical Research, Australian National University.
    Gage, P W
    Hippocampal GABA(A) channel conductance increased by diazepam.1997In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 388, no 6637, p. 71-5Article in journal (Refereed)
    Abstract [en]

    Benzodiazepines, which are widely used clinically for relief of anxiety and for sedation, are thought to enhance synaptic inhibition in the central nervous system by increasing the open probability of chloride channels activated by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Here we show that the benzodiazepine diazepam can also increase the conductance of GABAA channels activated by low concentrations of GABA (0.5 or 5 microM) in rat cultured hippocampal neurons. Before exposure to diazepam, chloride channels activated by GABA had conductances of 8 to 53pS. Diazepam caused a concentration-dependent and reversible increase in the conductance of these channels towards a maximum conductance of 70-80 pS and the effect was as great as 7-fold in channels of lowest initial conductance. Increasing the conductance of GABAA channels tonically activated by low ambient concentrations of GABA in the extracellular environment may be an important way in which these drugs depress excitation in the central nervous system. That any drug has such a large effect on single channel conductance has not been reported previously and has implications for models of channel structure and conductance.

  • 80.
    Ehrenberg, Måns
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Protein synthesis: Translocation in slow motion2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7304, p. 325-326Article in journal (Refereed)
  • 81. Ehret, Georg B.
    et al.
    Munroe, Patricia B.
    Rice, Kenneth M.
    Bochud, Murielle
    Johnson, Andrew D.
    Chasman, Daniel I.
    Smith, Albert V.
    Tobin, Martin D.
    Verwoert, Germaine C.
    Hwang, Shih-Jen
    Pihur, Vasyl
    Vollenweider, Peter
    O'Reilly, Paul F.
    Amin, Najaf
    Bragg-Gresham, Jennifer L.
    Teumer, Alexander
    Glazer, Nicole L.
    Launer, Lenore
    Zhao, Jing Hua
    Aulchenko, Yurii
    Heath, Simon
    Sober, Siim
    Parsa, Afshin
    Luan, Jian'an
    Arora, Pankaj
    Dehghan, Abbas
    Zhang, Feng
    Lucas, Gavin
    Hicks, Andrew A.
    Jackson, Anne U.
    Peden, John F.
    Tanaka, Toshiko
    Wild, Sarah H.
    Rudan, Igor
    Igl, Wilmar
    Milaneschi, Yuri
    Parker, Alex N.
    Fava, Cristiano
    Chambers, John C.
    Fox, Ervin R.
    Kumari, Meena
    Go, Min Jin
    van der Harst, Pim
    Kao, Wen Hong Linda
    Sjogren, Marketa
    Vinay, D. G.
    Alexander, Myriam
    Tabara, Yasuharu
    Shaw-Hawkins, Sue
    Whincup, Peter H.
    Liu, Yongmei
    Shi, Gang
    Kuusisto, Johanna
    Tayo, Bamidele
    Seielstad, Mark
    Sim, Xueling
    Nguyen, Khanh-Dung Hoang
    Lehtimaki, Terho
    Matullo, Giuseppe
    Wu, Ying
    Gaunt, Tom R.
    Onland-Moret, N. Charlotte
    Cooper, Matthew N.
    Platou, Carl G. P.
    Org, Elin
    Hardy, Rebecca
    Dahgam, Santosh
    Palmen, Jutta
    Vitart, Veronique
    Braund, Peter S.
    Kuznetsova, Tatiana
    Uiterwaal, Cuno S. P. M.
    Adeyemo, Adebowale
    Palmas, Walter
    Campbell, Harry
    Ludwig, Barbara
    Tomaszewski, Maciej
    Tzoulaki, Ioanna
    Palmer, Nicholette D.
    Aspelund, Thor
    Garcia, Melissa
    Chang, Yen-Pei C.
    O'Connell, Jeffrey R.
    Steinle, Nanette I.
    Grobbee, Diederick E.
    Arking, Dan E.
    Kardia, Sharon L.
    Morrison, Alanna C.
    Hernandez, Dena
    Najjar, Samer
    McArdle, Wendy L.
    Hadley, David
    Brown, Morris J.
    Connell, John M.
    Hingorani, Aroon D.
    Day, Ian N. M.
    Lawlor, Debbie A.
    Beilby, John P.
    Lawrence, Robert W.
    Clarke, Robert
    Hopewell, Jemma C.
    Ongen, Halit
    Dreisbach, Albert W.
    Li, Yali
    Young, J. Hunter
    Bis, Joshua C.
    Kahonen, Mika
    Viikari, Jorma
    Adair, Linda S.
    Lee, Nanette R.
    Chen, Ming-Huei
    Olden, Matthias
    Pattaro, Cristian
    Bolton, Judith A. Hoffman
    Koettgen, Anna
    Bergmann, Sven
    Mooser, Vincent
    Chaturvedi, Nish
    Frayling, Timothy M.
    Islam, Muhammad
    Jafar, Tazeen H.
    Erdmann, Jeanette
    Kulkarni, Smita R.
    Bornstein, Stefan R.
    Graessler, Juergen
    Groop, Leif
    Voight, Benjamin F.
    Kettunen, Johannes
    Howard, Philip
    Taylor, Andrew
    Guarrera, Simonetta
    Ricceri, Fulvio
    Emilsson, Valur
    Plump, Andrew
    Barroso, Ine S.
    Khaw, Kay-Tee
    Weder, Alan B.
    Hunt, Steven C.
    Sun, Yan V.
    Bergman, Richard N.
    Collins, Francis S.
    Bonnycastle, Lori L.
    Scott, Laura J.
    Stringham, Heather M.
    Peltonen, Leena
    Perola, Markus
    Vartiainen, Erkki
    Brand, Stefan-Martin
    Staessen, Jan A.
    Wang, Thomas J.
    Burton, Paul R.
    Artigas, Maria Soler
    Dong, Yanbin
    Snieder, Harold
    Wang, Xiaoling
    Zhu, Haidong
    Lohman, Kurt K.
    Rudock, Megan E.
    Heckbert, Susan R.
    Smith, Nicholas L.
    Wiggins, Kerri L.
    Doumatey, Ayo
    Shriner, Daniel
    Veldre, Gudrun
    Viigimaa, Margus
    Kinra, Sanjay
    Prabhakaran, Dorairaj
    Tripathy, Vikal
    Langefeld, Carl D.
    Rosengren, Annika
    Thelle, Dag S.
    Corsi, Anna Maria
    Singleton, Andrew
    Forrester, Terrence
    Hilton, Gina
    McKenzie, Colin A.
    Salako, Tunde
    Iwai, Naoharu
    Kita, Yoshikuni
    Ogihara, Toshio
    Ohkubo, Takayoshi
    Okamura, Tomonori
    Ueshima, Hirotsugu
    Umemura, Satoshi
    Eyheramendy, Susana
    Meitinger, Thomas
    Wichmann, H. -Erich
    Cho, Yoon Shin
    Kim, Hyung-Lae
    Lee, Jong-Young
    Scott, James
    Sehmi, Joban S.
    Zhang, Weihua
    Hedblad, Bo
    Nilsson, Peter
    Smith, George Davey
    Wong, Andrew
    Narisu, Narisu
    Stancakova, Alena
    Raffel, Leslie J.
    Yao, Jie
    Kathiresan, Sekar
    O'Donnell, Christopher J.
    Schwartz, Stephen M.
    Ikram, M. Arfan
    Longstreth, W. T., Jr.
    Mosley, Thomas H.
    Seshadri, Sudha
    Shrine, Nick R. G.
    Wain, Louise V.
    Morken, Mario A.
    Swift, Amy J.
    Laitinen, Jaana
    Prokopenko, Inga
    Zitting, Paavo
    Cooper, Jackie A.
    Humphries, Steve E.
    Danesh, John
    Rasheed, Asif
    Goel, Anuj
    Hamsten, Anders
    Watkins, Hugh
    Bakker, Stephan J. L.
    van Gilst, Wiek H.
    Janipalli, Charles S.
    Mani, K. Radha
    Yajnik, Chittaranjan S.
    Hofman, Albert
    Mattace-Raso, Francesco U. S.
    Oostra, Ben A.
    Demirkan, Ayse
    Isaacs, Aaron
    Rivadeneira, Fernando
    Lakatta, Edward G.
    Orru, Marco
    Scuteri, Angelo
    Ala-Korpela, Mika
    Kangas, Antti J.
    Lyytikainen, Leo-Pekka
    Soininen, Pasi
    Tukiainen, Taru
    Wurtz, Peter
    Ong, Rick Twee-Hee
    Doerr, Marcus
    Kroemer, Heyo K.
    Voelker, Uwe
    Voelzke, Henry
    Galan, Pilar
    Hercberg, Serge
    Lathrop, Mark
    Zelenika, Diana
    Deloukas, Panos
    Mangino, Massimo
    Spector, Tim D.
    Zhai, Guangju
    Meschia, James F.
    Nalls, Michael A.
    Sharma, Pankaj
    Terzic, Janos
    Kumar, M. V. Kranthi
    Denniff, Matthew
    Zukowska-Szczechowska, Ewa
    Wagenknecht, Lynne E.
    Fowkes, F. Gerald R.
    Charchar, Fadi J.
    Schwarz, Peter E. H.
    Hayward, Caroline
    Guo, Xiuqing
    Rotimi, Charles
    Bots, Michiel L.
    Brand, Eva
    Samani, Nilesh J.
    Polasek, Ozren
    Talmud, Philippa J.
    Nyberg, Fredrik
    Kuh, Diana
    Laan, Maris
    Hveem, Kristian
    Palmer, Lyle J.
    van der Schouw, Yvonne T.
    Casas, Juan P.
    Mohlke, Karen L.
    Vineis, Paolo
    Raitakari, Olli
    Ganesh, Santhi K.
    Wong, Tien Y.
    Tai, E. Shyong
    Cooper, Richard S.
    Laakso, Markku
    Rao, Dabeeru C.
    Harris, Tamara B.
    Morris, Richard W.
    Dominiczak, Anna F.
    Kivimaki, Mika
    Marmot, Michael G.
    Miki, Tetsuro
    Saleheen, Danish
    Chandak, Giriraj R.
    Coresh, Josef
    Navis, Gerjan
    Salomaa, Veikko
    Han, Bok-Ghee
    Zhu, Xiaofeng
    Kooner, Jaspal S.
    Melander, Olle
    Ridker, Paul M.
    Bandinelli, Stefania
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Wright, Alan F.
    Wilson, James F.
    Ferrucci, Luigi
    Farrall, Martin
    Tuomilehto, Jaakko
    Pramstaller, Peter P.
    Elosua, Roberto
    Soranzo, Nicole
    Sijbrands, Eric J. G.
    Altshuler, David
    Loos, Ruth J. F.
    Shuldiner, Alan R.
    Gieger, Christian
    Meneton, Pierre
    Uitterlinden, Andre G.
    Wareham, Nicholas J.
    Gudnason, Vilmundur
    Rotter, Jerome I.
    Rettig, Rainer
    Uda, Manuela
    Strachan, David P.
    Witteman, Jacqueline C. M.
    Hartikainen, Anna-Liisa
    Beckmann, Jacques S.
    Boerwinkle, Eric
    Vasan, Ramachandran S.
    Boehnke, Michael
    Larson, Martin G.
    Jarvelin, Marjo-Riitta
    Psaty, Bruce M.
    Abecasis, Goncalo R.
    Chakravarti, Aravinda
    Elliott, Paul
    van Duijn, Cornelia M.
    Newton-Cheh, Christopher
    Levy, Daniel
    Caulfield, Mark J.
    Johnson, Toby
    Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk2011In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 478, no 7367, p. 103-109Article in journal (Refereed)
    Abstract [en]

    Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

  • 82.
    Ellegren, Hans
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Sheldon, Ben C.
    Genetic basis of fitness differences in natural populations2008In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 452, no 7184, p. 169-175Article, review/survey (Refereed)
    Abstract [en]

    Genomics profoundly influences current biology. One of many exciting consequences of this revolution is the potential for identifying and studying the genetic basis of those traits affecting fitness that are key to natural selection. Recent studies using a multitude of genomic approaches have established such genotype - phenotype relationships in natural populations, giving new insight into the genetic architecture of quantitative variation. In parallel, an emerging understanding of the quantitative genetics of fitness variation in the wild means that we are poised to see a synthesis of ecological and molecular approaches in evolutionary biology.

  • 83.
    Ellegren, Hans
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Smeds, Linnea
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Burri, Reto
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Ólason, Páll I.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Backström, Niclas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Kawakami, Takeshi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Künstner, Axel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Mäkinen, Hannu
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Nadachowska-Brzyska, Krystyna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Qvarnström, Anna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal Ecology.
    Uebbing, Severin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Wolf, Jochen B. W.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    The genomic landscape of species divergence in Ficedula flycatchers2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 491, no 7426, p. 756-760Article in journal (Refereed)
    Abstract [en]

    Unravelling the genomic landscape of divergence between lineages is key to understanding speciation. The naturally hybridizing collared flycatcher and pied flycatcher are important avian speciation models that show pre-as well as postzygotic isolation. We sequenced and assembled the 1.1-Gb flycatcher genome, physically mapped the assembly to chromosomes using a low-density linkage map and re-sequenced population samples of each species. Here we show that the genomic landscape of species differentiation is highly heterogeneous with approximately 50 'divergence islands' showing up to 50-fold higher sequence divergence than the genomic background. These non-randomly distributed islands, with between one and three regions of elevated divergence per chromosome irrespective of chromosome size, are characterized by reduced levels of nucleotide diversity, skewed allele-frequency spectra, elevated levels of linkage disequilibrium and reduced proportions of shared polymorphisms in both species, indicative of parallel episodes of selection. Proximity of divergence peaks to genomic regions resistant to sequence assembly, potentially including centromeres and telomeres, indicate that complex repeat structures may drive species divergence. A much higher background level of species divergence of the Z chromosome, and a lower proportion of shared polymorphisms, indicate that sex chromosomes and autosomes are at different stages of speciation. This study provides a roadmap to the emerging field of speciation genomics.

  • 84.
    Eme, Laura
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The eukaryotic ancestor shapes up2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 562, no 7727, p. 352-354Article in journal (Other academic)
    Abstract [en]

    Asgard archaea are the closest known relatives of nucleus-bearing organisms called eukaryotes. A study indicates that these archaea have a dynamic network of actin protein - a trait thought of as eukaryote-specific.

  • 85.
    Ettema, Thijs J. G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mitochondria in the second act2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 531, no 7592, p. 39-40Article in journal (Other academic)
    Abstract [en]

    A large phylogenomics study reveals that the symbiotic event that led to the emergence of organelles known as mitochondria may have occurred later in the evolution of complex cells than was thought.

  • 86.
    Evans, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Sports doping vastly underestimated2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 519, no 7541, p. 33-33Article in journal (Refereed)
  • 87.
    Fuchsberger, Christian
    et al.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.;Univ Lubeck, European Acad Bolzano Bozen EURAC, Ctr Biomed, Bolzano, Italy..
    Flannick, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Agarwala, Vineeta
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA..
    Gaulton, Kyle J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Ma, Clement
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Fontanillas, Pierre
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Moutsianas, Loukas
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    McCarthy, Davis J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Rivas, Manuel A.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Perry, John R. B.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England.;Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Blackwell, Thomas W.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Robertson, Neil R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Rayner, N. William
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Cingolani, Pablo
    McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.;McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Tajes, Juan Fernandez
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Human Genet Ctr, Houston, TX 77030 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Chines, Peter S.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Hartl, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Chen, Han
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Huyghe, Jeroen R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    van de Bunt, Martijn
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Pearson, Richard D.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Kumar, Ashish
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Basel, Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol, Basel, Switzerland..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Gamazon, Eric R.
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Lee, Jaehoon
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Chen, Yuhui
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Below, Jennifer E.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Chen, Peng
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Huang, Jinyan
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Go, Min Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Stitzel, Michael L.
    Jackson Lab Genom Med, Farmington, CT USA..
    Pasko, Dorota
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Parker, Stephen C. J.
    Univ Michigan, Dept Computat Med, Ann Arbor, MI USA.;Univ Michigan, Dept Bioinformat & Human Genet, Ann Arbor, MI USA..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden..
    Green, Todd
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Beer, Nicola L.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Day-Williams, Aaron G.
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Fingerlin, Tasha
    Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA..
    Horikoshi, Momoko
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hu, Cheng
    Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Huh, Iksoo
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Ikram, Mohammad Kamran
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Kim, Yongkang
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Kwon, Min-Seok
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Lee, Juyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Lee, Selyeong
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Lin, Keng-Han
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Maxwell, Taylor J.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Nagai, Yoshihiko
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada..
    Wang, Xu
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Welch, Ryan P.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Yoon, Joon
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Zhang, Weihua
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA..
    Voight, Benjamin F.
    Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Jenkinson, Christopher P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.;South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Manning, Alisa
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Balkau, Beverley
    INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France..
    Stancakova, Alena
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland..
    Abboud, Hanna E.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India..
    Gottesman, Omri
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Scott, James
    Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Carey, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Grant, George
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Smith, Joshua D.
    Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA..
    Neale, Benjamin M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA..
    Purcell, Shaun
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Psychiat, New York, NY 10029 USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Lee, Heung Man
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Kwak, Soo-Heon
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea..
    Zhao, Wei
    Univ Penn, Dept Med, Philadelphia, PA 19104 USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Lam, Vincent K. L.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Park, Kyong Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea.;Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea.;Seoul Natl Univ, Coll Med, Seoul, South Korea..
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    So, Wing Yee
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Tam, Claudia H. T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Afzal, Uzma
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Aguilar, David
    Baylor Coll Med, Div Cardiovasc, Houston, TX 77030 USA..
    Arya, Rector
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Aung, Tin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Chan, Edmund
    Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Navarro, Carmen
    IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.;Univ Murcia, CIBERESP, Murcia, Spain.;Univ Murcia, Sch Med, Unit Prevent Med & Publ Hlth, E-30001 Murcia, Spain..
    Cheng, Ching-Yu
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Florence, Italy..
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Curran, Joanne E.
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Rybin, Denis
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Farook, Vidya S.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Fowler, Sharon P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Freedman, Barry I.
    Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA..
    Griswold, Michael
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Hale, Daniel Esten
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Hicks, Pamela J.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Khor, Chiea-Chuen
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    Kumar, Satish
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Lehne, Benjamin
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Thuillier, Dorothee
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Lim, Wei Yen
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Liu, Jianjun
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Loh, Marie
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland.;ASTAR, TLGM, Singapore, Singapore..
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Puppala, Sobha
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Scott, William R.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Yengo, Loic
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Taylor, Herman A., Jr.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Thameem, Farook
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Wilson, Gregory, Sr.
    Jackson State Univ, Coll Publ Serv, Jackson, MS USA..
    Wong, Tien Yin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Njolstad, Pal Rasmus
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Dept Pediat, Bergen, Norway..
    Levy, Jonathan C.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Schwarzmayr, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Surdulescu, Gabriela L.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Herder, Christian
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Wieland, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark.;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark..
    Christensen, Cramer
    Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Minerva Fdn, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland..
    Doney, Alex S. F.
    Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA..
    Farmer, Andrew J.
    Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England..
    Hakaste, Liisa
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland..
    Hodgkiss, Dylan
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Kravic, Jasmina
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Lyssenko, Valeriya
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Hollensted, Mette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Jorgensen, Torben
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, Copenhagen, Denmark.;Aalborg Univ, Med, Aalborg, Denmark..
    Ladenvall, Claes
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland..
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Rathmann, Wolfgang
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lauritzen, Torsten
    Aarhus Univ, Sect Gen Practice, Dept Publ Hlth, Aarhus, Denmark..
    Narisu, Narisu
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Melander, Olle
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc, Malmo, Sweden..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden..
    Qi, Lu
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Qi, Qibin
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA..
    Roden, Michael
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Swift, Amy
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Rosengren, Anders H.
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Stirrups, Kathleen
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Blancher, Christine
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Carneiro, Mauricio O.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Maguire, Jared
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Poplin, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Shakir, Khalid
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Fennell, Timothy
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    DePristo, Mark
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    de Angelis, Martin Hrabe
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany.;Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, Freising Weihenstephan, Germany..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jun, Goo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Nilsson, Peter
    Lund Univ, Dept Clin Sci, Med, Malmo, Sweden..
    Murphy, Jacquelyn
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Onofrio, Robert
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark..
    Meisinger, Christa
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Hu, Frank B.
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Peters, Annette
    Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Huth, Cornelia
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    O'Rahilly, Stephen P.
    Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England..
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Autonomous Univ Madrid, Univ Hosp LaPaz, Inst Invest Sanitaria Hosp Univ LaPaz IdiPAZ, Madrid, Spain.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Watanabe, Richard M.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dabet & Obes Res Inst, Los Angeles, CA USA..
    Syvanen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergman, Richard N.
    Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA..
    Bharadwaj, Dwaipayan
    CSIR IGIB, Funct Genom Unit, New Delhi, India..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea..
    Chandak, Giriraj R.
    CSIR Ctr Cellular & Mol Biol, Hyderabad, Telangana, India..
    Chan, Juliana C. N.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    Chia, Kee Seng
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Daly, Mark J.
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Ebrahim, Shah B.
    Ctr Chron Dis Control, New Delhi, India..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Jablonski, Kathleen A.
    George Washington Univ, Biostat Ctr, Rockville, MD USA..
    Lehman, Donna M.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Jia, Weiping
    Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Ma, Ronald C. W.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    Pollin, Toni I.
    Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Sandhu, Manjinder
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Tandon, Nikhil
    All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India..
    Froguel, Philippe
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England..
    Teo, Yik Ying
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Inst Life Sci, Singapore, Singapore.;Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany..
    DeFronzo, Ralph A.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Glaser, Benjamin
    Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Banks, Eric
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Gieger, Christian
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Im, Hae Kyung
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Illig, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, NH, Germany.;Hannover Med Sch, Inst Human Genet, Hannover, NH, Germany..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Buck, Gemma
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Trakalo, Joseph
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Buck, David
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Prokopenko, Inga
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farjoun, Yossi
    Broad Inst, Data Sci & Data Engn, Cambridge, MA USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Gloyn, Anna L.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Tuomi, Tiinamaija
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.;Univ Helsinki, FIMM, Helsinki, Finland..
    Kooner, Jaspal Singh
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Lee, Jong-Young
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Park, Taesung
    Seoul Natl Univ, Dept Stat, Seoul, South Korea.;Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Donnelly, Peter
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Hattersley, Andrew T.
    Univ Exeter, Sch Med, Exeter, Devon, England..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Collins, Francis S.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Atzmon, Gil
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA.;Univ Haifa, Dept Nat Sci, Haifa, Israel..
    Chambers, John C.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Laakso, Markku
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Strom, Tim M.
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Bell, Graeme I.
    Univ Chicago, Dept Med Genet, Chicago, IL 60637 USA.;Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA..
    Blangero, John
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Duggirala, Ravindranath
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Tai, E. Shyong
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.;Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, Singapore..
    McVean, Gilean
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Hanis, Craig L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Seielstad, Mark
    Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.;Blood Syst Res Inst, San Francisco, CA USA..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Meigs, James B.
    Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Cox, Nancy J.
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Sladek, Rob
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada..
    Lander, Eric S.
    Broad Inst MIT & Harvard, Cambridge, MA USA..
    Gabriel, Stacey
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Meitinger, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Groop, Leif
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.;Univ Helsinki, FIMM, Helsinki, Finland..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Florez, Jose C.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA..
    Scott, Laura J.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Kang, Hyun Min
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Altshuler, David
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.;MIT, Dept Biol, Cambridge, MA USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    The genetic architecture of type 2 diabetes2016In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 536, no 7614, p. 41-47Article in journal (Refereed)
    Abstract [en]

    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

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    Jacques, Sylvain A.
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    Schultz, Niklas
    Lundback, Thomas
    Einarsdottir, Berglind Osk
    Saleh, Aljona
    Gokturk, Camilla
    Baranczewski, Pawel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Svensson, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Berntsson, Ronnie P. -A.
    Gustafsson, Robert
    Stromberg, Kia
    Sanjiv, Kumar
    Jacques-Cordonnier, Marie-Caroline
    Desroses, Matthieu
    Gustavsson, Anna-Lena
    Olofsson, Roger
    Johansson, Fredrik
    Homan, Evert J.
    Loseva, Olga
    Brautigam, Lars
    Johansson, Lars
    Hoglund, Andreas
    Hagenkort, Anna
    Pham, Therese
    Altun, Mikael
    Gaugaz, Fabienne Z.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Vikingsson, Svante
    Evers, Bastiaan
    Henriksson, Martin
    Vallin, Karl S. A.
    Wallner, Olov A.
    Hammarstrom, Lars G. J.
    Wiita, Elisee
    Almlof, Ingrid
    Kalderen, Christina
    Axelsson, Hanna
    Djureinovic, Tatjana
    Puigvert, Jordi Carreras
    Haggblad, Maria
    Jeppsson, Fredrik
    Martens, Ulf
    Lundin, Cecilia
    Lundgren, Bo
    Granelli, Ingrid
    Jensen, Annika Jenmalm
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nilsson, Jonas A.
    Stenmark, Pal
    Scobie, Martin
    Berglund, Ulrika Warpman
    Helleday, Thomas
    MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool2014In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 508, no 7495, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.

  • 89. Garrouste, Romain
    et al.
    Clement, Gael
    Nel, Patricia
    Engel, Michael S.
    Grandcolas, Philippe
    D'Haese, Cyrille A.
    Lagebro, Linda
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Denayer, Julien
    Gueriau, Pierre
    Lafaite, Patrick
    Olive, Sebastien
    Prestianni, Cyrille
    Nel, Andre
    Is Strudiella a Devonian insect?: Reply2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 494, no 7437, p. E4-E5Article in journal (Refereed)
  • 90. Garrouste, Romain
    et al.
    Clement, Gael
    Nel, Patricia
    Engel, Michael S.
    Grandcolas, Philippe
    D'Haese, Cyrille
    Lagebro, Linda
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology.
    Denayer, Julien
    Gueriau, Pierre
    Lafaite, Patrick
    Olive, Sebastien
    Prestianni, Cyrille
    Nel, Andre
    A complete insect from the Late Devonian period2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 488, no 7409, p. 82-85Article in journal (Refereed)
    Abstract [en]

    After terrestrialization, the diversification of arthropods and vertebrates is thought to have occurred in two distinct phases(1), the first between the Silurian and the Frasnian stages (Late Devonian period) (425-385 million years (Myr) ago), and the second characterized by the emergence of numerous new major taxa, during the Late Carboniferous period (after 345 Myr ago). These two diversification periods bracket the depauperate vertebrate Romer's gap (360-345 Myr ago) and arthropod gap (385-325 Myr ago)(1), which could be due to preservational artefact(2,3). Although a recent molecular dating has given an age of 390 Myr for the Holometabola(4), the record of hexapods during the Early-Middle Devonian (411.5-391 Myr ago, Pragian to Givetian stages) is exceptionally sparse and based on fragmentary remains, which hinders the timing of this diversification. Indeed, although Devonian Archaeognatha are problematic(5,6), the Pragian of Scotland has given some Collembola and the incomplete insect Rhyniognatha, with its diagnostic dicondylic, metapterygotan mandibles(5,7). The oldest, definitively winged insects are from the Serpukhovian stage (latest Early Carboniferous period)(8). Here we report the first complete Late Devonian insect, which was probably a terrestrial species. Its 'orthopteroid' mandibles are of an omnivorous type, clearly not modified for a solely carnivorous diet. This discovery narrows the 45-Myr gap in the fossil record of Hexapoda, and demonstrates [GRAPHICS] further a first Devonian phase of diversification for the Hexapoda, as in vertebrates, and suggests that the Pterygota diversified before and during Romer's gap.

  • 91. George, Julie
    et al.
    Lim, Jing Shan
    Jang, Se Jin
    Cun, Yupeng
    Ozretic, Luka
    Kong, Gu
    Leenders, Frauke
    Lu, Xin
    Fernandez-Cuesta, Lynnette
    Bosco, Graziella
    Mueller, Christian
    Dahmen, Ilona
    Jahchan, Nadine S.
    Park, Kwon-Sik
    Yang, Dian
    Karnezis, Anthony N.
    Vaka, Dedeepya
    Torres, Angela
    Wang, Maia Segura
    Korbel, Jan O.
    Menon, Roopika
    Chun, Sung-Min
    Kim, Deokhoon
    Wilkerson, Matt
    Hayes, Neil
    Engelmann, David
    Puetzer, Brigitte
    Bos, Marc
    Michels, Sebastian
    Vlasic, Ignacija
    Seidel, Danila
    Pinther, Berit
    Schaub, Philipp
    Becker, Christian
    Altmueller, Janine
    Yokota, Jun
    Kohno, Takashi
    Iwakawa, Reika
    Tsuta, Koji
    Noguchi, Masayuki
    Muley, Thomas
    Hoffmann, Hans
    Schnabel, Philipp A.
    Petersen, Iver
    Chen, Yuan
    Soltermann, Alex
    Tischler, Verena
    Choi, Chang-min
    Kim, Yong-Hee
    Massion, Pierre P.
    Zou, Yong
    Jovanovic, Dragana
    Kontic, Milica
    Wright, Gavin M.
    Russell, Prudence A.
    Solomon, Benjamin
    Koch, Ina
    Lindner, Michael
    Muscarella, Lucia A.
    la Torre, Annamaria
    Field, John K.
    Jakopovic, Marko
    Knezevic, Jelena
    Castanos-Velez, Esmeralda
    Roz, Luca
    Pastorino, Ugo
    Brustugun, Odd-Terje
    Lund-Iversen, Marius
    Thunnissen, Erik
    Koehler, Jens
    Schuler, Martin
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Sanchez-Cespedes, Montserrat
    Salvesen, Helga B.
    Achter, Viktor
    Lang, Ulrich
    Bogus, Magdalena
    Schneider, Peter M.
    Zander, Thomas
    Ansen, Sascha
    Hallek, Michael
    Wolf, Juergen
    Vingron, Martin
    Yatabe, Yasushi
    Travis, William D.
    Nuernberg, Peter
    Reinhardt, Christian
    Perner, Sven
    Heukamp, Lukas
    Buettner, Reinhard
    Haas, Stefan A.
    Brambilla, Elisabeth
    Peifer, Martin
    Sage, Julien
    Thomas, Roman K.
    Comprehensive genomic profiles of small cell lung cancer2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 524, no 7563, p. 47-U73Article in journal (Refereed)
    Abstract [en]

    We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

  • 92. Groenen, M. A.
    et al.
    Archibald, A. L.
    Uenishi, H.
    Tuggle, C. K.
    Takeuchi, Y.
    Rothschild, M. F.
    Rogel-Gaillard, C.
    Park, C.
    Milan, D.
    Megens, H. J.
    Li, S.
    Larkin, D. M.
    Kim, H.
    Frantz, L. A.
    Caccamo, M.
    Ahn, H.
    Aken, B. L.
    Anselmo, A.
    Anthon, C.
    Auvil, L.
    Badaoui, B.
    Beattie, C. W.
    Bendixen, C.
    Berman, D.
    Blecha, F.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Bolund, L.
    Bosse, M.
    Botti, S.
    Bujie, Z.
    Byström, M.
    Capitanu, B.
    Carvalho-Silva, D.
    Chardon, P.
    Chen, C.
    Cheng, R.
    Choi, S. H.
    Chow, W.
    Clark, R. C.
    Clee, C.
    Crooijmans, R. P.
    Dawson, H. D.
    Dehais, P.
    De Sapio, F.
    Dibbits, B.
    Drou, N.
    Du, Z. Q.
    Eversole, K.
    Fadista, J.
    Fairley, S.
    Faraut, T.
    Faulkner, G. J.
    Fowler, K. E.
    Fredholm, M.
    Fritz, E.
    Gilbert, J. G.
    Giuffra, E.
    Gorodkin, J.
    Griffin, D. K.
    Harrow, J. L.
    Hayward, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Howe, K.
    Hu, Z. L.
    Humphray, S. J.
    Hunt, T.
    Hornshoj, H.
    Jeon, J. T.
    Jern, Patric
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jones, M.
    Jurka, J.
    Kanamori, H.
    Kapetanovic, R.
    Kim, J.
    Kim, J. H.
    Kim, K. W.
    Kim, T. H.
    Larson, G.
    Lee, K.
    Lee, K. T.
    Leggett, R.
    Lewin, H. A.
    Li, Y.
    Liu, W.
    Loveland, J. E.
    Lu, Y.
    Lunney, J. K.
    Ma, J.
    Madsen, O.
    Mann, K.
    Matthews, L.
    McLaren, S.
    Morozumi, T.
    Murtaugh, M. P.
    Narayan, J.
    Nguyen, D. T.
    Ni, P.
    Oh, S. J.
    Onteru, S.
    Panitz, F.
    Park, E. W.
    Park, H. S.
    Pascal, G.
    Paudel, Y.
    Perez-Enciso, M.
    Ramirez-Gonzalez, R.
    Reecy, J. M.
    Rodriguez-Zas, S.
    Rohrer, G. A.
    Rund, L.
    Sang, Y.
    Schachtschneider, K.
    Schraiber, J. G.
    Schwartz, J.
    Scobie, L.
    Scott, C.
    Searle, S.
    Servin, B.
    Southey, B. R.
    Sperber, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Stadler, P.
    Sweedler, J. V.
    Tafer, H.
    Thomsen, B.
    Wali, R.
    Wang, J.
    White, S.
    Xu, X.
    Yerle, M.
    Zhang, G.
    Zhang, J.
    Zhao, S.
    Rogers, J.
    Churcher, C.
    Schook, L. B.
    Analyses of pig genomes provide insight into porcine demography and evolution2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 491, no 7424, p. 393-398Article in journal (Refereed)
    Abstract [en]

    For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

  • 93.
    Gudasz, Cristian
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Bastviken, David
    Steger, Kristin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Premke, Katrin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Sobek, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Tranvik, Lars J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Temperature-controlled organic carbon mineralization in lake sediments2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 466, no 7305, p. 478-481Article in journal (Refereed)
    Abstract [en]

    Peatlands, soils and the ocean floor are well-recognized as sites of organic carbonaccumulation andrepresentimportant global carbon sinks(1,2). Although the annual burial of organic carbon in lakes and reservoirs exceeds that of ocean sediments(3), these inland waters are components of the global carbon cycle that receive only limited attention(4-6). Of the organic carbon that is being deposited onto the sediments, a certain proportion will be mineralized and the remainder will be buried over geological timescales. Here we assess the relationship between sediment organic carbon mineralization and temperature in a cross-system survey of boreal lakes in Sweden, and with input froma compilation of published data from awide range of lakes that differ with respect to climate, productivity and organic carbon source. We find that the mineralization of organic carbon in lake sediments exhibits a strongly positive relationship with temperature, which suggests that warmer water temperatures lead to more mineralization and less organic carbon burial. Assuming that future organic carbon delivery to the lake sediments will be similar to that under present-day conditions, we estimate that temperature increases following the latest scenarios presented by the Intergovernmental Panel on Climate Change(7) could result in a 4-27 per cent (0.9-6.4 Tg Cyr(-1)) decrease in annual organic carbon burial in boreal lakes.

  • 94.
    Gustafsson, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Astronomy and Space Physics.
    Sanctions against scientists threaten progress2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 461, no 7265, p. 723-723Article in journal (Refereed)
  • 95.
    Gustafsson, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Astronomy and Space Physics.
    Scientists should promote co-operation, not boycott2007In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 447, no 7147, p. 908-908Article in journal (Refereed)
  • 96. Haas, Brian J.
    et al.
    Kamoun, Sophien
    Zody, Michael C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Jiang, Rays H. Y.
    Handsaker, Robert E.
    Cano, Liliana M.
    Grabherr, Manfred
    Kodira, Chinnappa D.
    Raffaele, Sylvain
    Torto-Alalibo, Trudy
    Bozkurt, Tolga O.
    Ah-Fong, Audrey M. V.
    Alvarado, Lucia
    Anderson, Vicky L.
    Armstrong, Miles R.
    Avrova, Anna
    Baxter, Laura
    Beynon, Jim
    Boevink, Petra C.
    Bollmann, Stephanie R.
    Bos, Jorunn I. B.
    Bulone, Vincent
    Cai, Guohong
    Cakir, Cahid
    Carrington, James C.
    Chawner, Megan
    Conti, Lucio
    Costanzo, Stefano
    Ewan, Richard
    Fahlgren, Noah
    Fischbach, Michael A.
    Fugelstad, Johanna
    Gilroy, Eleanor M.
    Gnerre, Sante
    Green, Pamela J.
    Grenville-Briggs, Laura J.
    Griffith, John
    Gruenwald, Niklaus J.
    Horn, Karolyn
    Horner, Neil R.
    Hu, Chia-Hui
    Huitema, Edgar
    Jeong, Dong-Hoon
    Jones, Alexandra M. E.
    Jones, Jonathan D. G.
    Jones, Richard W.
    Karlsson, Elinor K.
    Kunjeti, Sridhara G.
    Lamour, Kurt
    Liu, Zhenyu
    Ma, LiJun
    MacLean, Daniel
    Chibucos, Marcus C.
    McDonald, Hayes
    McWalters, Jessica
    Meijer, Harold J. G.
    Morgan, William
    Morris, Paul F.
    Munro, Carol A.
    O'Neill, Keith
    Ospina-Giraldo, Manuel
    Pinzon, Andres
    Pritchard, Leighton
    Ramsahoye, Bernard
    Ren, Qinghu
    Restrepo, Silvia
    Roy, Sourav
    Sadanandom, Ari
    Savidor, Alon
    Schornack, Sebastian
    Schwartz, David C.
    Schumann, Ulrike D.
    Schwessinger, Ben
    Seyer, Lauren
    Sharpe, Ted
    Silvar, Cristina
    Song, Jing
    Studholme, David J.
    Sykes, Sean
    Thines, Marco
    van de Vondervoort, Peter J. I.
    Phuntumart, Vipaporn
    Wawra, Stephan
    Weide, Rob
    Win, Joe
    Young, Carolyn
    Zhou, Shiguo
    Fry, William
    Meyers, Blake C.
    van West, Pieter
    Ristaino, Jean
    Govers, Francine
    Birch, Paul R. J.
    Whisson, Stephen C.
    Judelson, Howard S.
    Nusbaum, Chad
    Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans2009In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 461, no 7262, p. 393-398Article in journal (Refereed)
    Abstract [en]

    Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

  • 97. Hagberg, Carolina E.
    et al.
    Falkevall, Annelie
    Wang, Xun
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Huusko, Jenni
    Nilsson, Ingrid
    van Meeteren, Laurens A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Samen, Erik
    Lu, Li
    Vanwildemeersch, Maarten
    Klar, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Genove, Guillem
    Pietras, Kristian
    Stone-Elander, Sharon
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ylä-Herttuala, Seppo
    Lindahl, Per
    Eriksson, Ulf
    Vascular endothelial growth factor B controls endothelial fatty acid uptake2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 464, no 7290, p. 917-921Article in journal (Refereed)
    Abstract [en]

    The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology. However, the detailed role of VEGF-B in blood vessel function has remained unclear. Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood. Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb(-/-) mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.

  • 98.
    Hansson, Mats G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Biobanks: Validate gene findings before telling donors2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 484, no 7395, p. 455-455Article in journal (Refereed)
  • 99. Harrison, John A.
    et al.
    Barros, Nathan
    Bastviken, David
    Deemer, Bridget
    Evans, Christopher
    Grinham, Alistair
    Harby, Atle
    Lovelock, Catherine
    Peacock, Michael
    Prairie, Yves
    Sherman, Bradford
    Sobek, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Tranvik, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Dams: weigh pros and cons case by case2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 568, no 7751, p. 171-171Article in journal (Other (popular science, discussion, etc.))
  • 100.
    Hashimoto, Takuya
    et al.
    Osaka Sangyo Univ, Dept Environm Sci & Technol, Fac Design Technol, Osaka, Japan;Natl Astron Observ Japan, Tokyo, Japan.
    Laporte, Nicolas
    UCL, Dept Phys & Astron, London, England;Univ Toulouse, CNRS, IRAP, UPS,CNES, Toulouse, France.
    Mawatari, Ken
    Osaka Sangyo Univ, Dept Environm Sci & Technol, Fac Design Technol, Osaka, Japan.
    Ellis, Richard S.
    UCL, Dept Phys & Astron, London, England.
    Inoue, Akio K.
    Osaka Sangyo Univ, Dept Environm Sci & Technol, Fac Design Technol, Osaka, Japan.
    Zackrisson, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Observational Astronomy.
    Roberts-Borsani, Guido
    UCL, Dept Phys & Astron, London, England.
    Zheng, Wei
    Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
    Tamura, Yoichi
    Nagoya Univ, Grad Sch Sci, Div Particle & Astrophys Sci, Nagoya, Aichi, Japan.
    Bauer, Franz E.
    Pontificia Univ Catolica Chile, Fac Fis, Inst Astrofis, Santiago, Chile;Pontificia Univ Catolica Chile, Fac Fis, Ctr Astroingn, Santiago, Chile;Space Sci Inst, Boulder, CO USA.
    Fletcher, Thomas
    UCL, Dept Phys & Astron, London, England.
    Harikane, Yuichi
    Univ Tokyo, Inst Cosm Ray Res, Chiba, Japan;Univ Tokyo, Grad Sch Sci, Dept Phys, Tokyo, Japan.
    Hatsukade, Bunyo
    Univ Tokyo, Inst Astron, Tokyo, Japan.
    Hayatsu, Natsuki H.
    Univ Tokyo, Grad Sch Sci, Dept Phys, Tokyo, Japan;European Southern Observ, Garching, Germany.
    Matsuda, Yuichi
    Natl Astron Observ Japan, Tokyo, Japan;Grad Univ Adv Studies SOKENDAI, Sch Phys Sci, Dept Astron Sci, Tokyo, Japan.
    Matsuo, Hiroshi
    Natl Astron Observ Japan, Tokyo, Japan;Grad Univ Adv Studies SOKENDAI, Sch Phys Sci, Dept Astron Sci, Tokyo, Japan.
    Okamoto, Takashi
    Hokakido Univ, Dept Cosmosci, Grad Sch Sci, Sapporo, Hokkaido, Japan.
    Ouchi, Masami
    Univ Tokyo, Inst Cosm Ray Res, Chiba, Japan;Univ Tokyo, Kavli Inst Phys & Math Universe WPI, Todai Inst Adv Study, Chiba, Japan.
    Pello, Roser
    Univ Toulouse, CNRS, IRAP, UPS,CNES, Toulouse, France.
    Rydberg, Claes-Erik
    Heidelberg Univ, Zentrum Astron, Inst Theoret Astrophys, Heidelberg, Germany.
    Shimizu, Ikkoh
    Osaka Univ, Dept Earth & Space Sci, Theoret Astrophys, Osaka, Japan.
    Taniguchi, Yoshiaki
    Open Univ Japan, Chiba, Japan.
    Umehata, Hideki
    Open Univ Japan, Chiba, Japan;Inst Phys & Chem Res RIKEN, Saitama, Japan.
    Yoshida, Naoki
    Univ Tokyo, Grad Sch Sci, Dept Phys, Tokyo, Japan;Univ Tokyo, Kavli Inst Phys & Math Universe WPI, Todai Inst Adv Study, Chiba, Japan.
    The onset of star formation 250 million years after the Big Bang2018In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 557, no 7705, p. 392-395Article in journal (Refereed)
    Abstract [en]

    A fundamental quest of modern astronomy is to locate the earliest galaxies and study how they influenced the intergalactic medium a few hundred million years after the Big Bang(1-3). The abundance of star-forming galaxies is known to decline(4,5) from redshifts of about 6 to 10, but a key question is the extent of star formation at even earlier times, corresponding to the period when the first galaxies might have emerged. Here we report spectroscopic observations of MACS1149-JD1(6), a gravitationally lensed galaxy observed when the Universe was less than four per cent of its present age. We detect an emission line of doubly ionized oxygen at a redshift of 9.1096 +/- 0.0006, with an uncertainty of one standard deviation. This precisely determined redshift indicates that the red rest-frame optical colour arises from a dominant stellar component that formed about 250 million years after the Big Bang, corresponding to a redshift of about 15. Our results indicate that it may be possible to detect such early episodes of star formation in similar galaxies with future telescopes.

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