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  • 51.
    Alarcon-Riquelme, Marta E.
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Fernández, C
    Expression of the B cell repertoire in lpr mice1995In: Clin Exp Immunol, Vol. 99, p. 262-Article in journal (Refereed)
  • 52.
    Alarcon-Riquelme, Marta E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Kozyrev, Sergey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Shared genes in rheumatic diseases: The role of PDCD1 and RUNX genes in disease susceptibility2006In: Hereditary Basis of Rheumatic Diseases, Basel: Birkhäuser , 2006, p. 79-85Chapter in book (Other academic)
  • 53.
    Alarcon-Riquelme, Marta E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Prokunina, Ludmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Finding genes for SLE: complex interactions and complex populations2003In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 21, no 2, p. 117p. 117-120Article in journal (Other academic)
    Abstract [en]

    Many years of work, multiplex family collection and endless genotyping finally give fruit. The original aim cannot be lost. The aim is not only to identify mutations involved in susceptibility for systemic lupus erythematosus (SLE) but to elucidate the disease pathogenesis as well. After genetics comes the biology. We review our recent findings on the genetics of lupus, provide possible mechanisms for disease susceptibility and present some facts on the problematic of identifying susceptibility mutations for complex diseases in complex human populations.

  • 54.
    Alarcon-Riquelme, Marta
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Wistrand, Per
    Department of Neuroscience.
    The Genetics of systemic lupus erythematosus: identification of hSLE12000In: Scandinavian Journal of Rheumatology, Vol. 29, p. 19-Article, book review (Other scientific)
  • 55.
    Alarcon-Riquelme, ME
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    A Runx Trio with a Taste for Autoimmunity2003In: Nat Genet, Vol. 35, p. 299Other (Other scientific)
  • 56.
    Alarcon-Riquelme, ME
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Family studies in SLE2002In: Rheumatology, Vol. 41, p. 364Other (Other scientific)
  • 57.
    Alarcon-Riquelme, ME
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Functional Genomics in the study of Autoimmune Diseases2003In: Autoimmunity Reviews , Vol. 2, p. 177Other (Other scientific)
  • 58.
    Alarcon-Riquelme, ME
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Lindqvist, AK
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Jonasson, I
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Johanneson, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Sandino, S
    Alcocer-Varela, J
    Granados, J
    Kristjansdottir, H
    Grondal, G
    Svenungsson, E
    Lundberg, I
    Steinsson, K
    Klareskog, L
    Sturfelt, G
    Truedsson, L
    Alarcon-Segovia, D
    Gyllensten, UB
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Genetic analysis of the contribution of IL10 to systemic lupuserythematosus.1999In: J Rheumatol, Vol. 26, p. 2148-Article in journal (Refereed)
  • 59. Alarcon-Segovia, D
    et al.
    Alarcon-Riquelme, Marta
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Etiopathogenesis of Systemic Lupus Erythematosus2003In: Ed. Lahita., Academic Press , 2003Chapter in book (Other scientific)
  • 60.
    Alarcón-Riquelme, Marta E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    The genetics of systemic lupus erythematosus: understanding how SNPs confer disease susceptibility.2006In: Springer Semin Immunopathol, ISSN 0344-4325, Vol. 28, no 2, p. 109-17Article in journal (Refereed)
  • 61.
    Alarcón-Riquelme, Marta E.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Collaborative network on the genetics of systemic lupus erythematosus: towards the determination of susceptibility loci through a genome-wide microsatellite scanning1996In: European Workshop of Rheumatology ResearchArticle, book review (Other scientific)
  • 62.
    Alarcón-Riquelme, Marta E.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Cooperative Network on the genetics of systemic lupus erythematosus1998In: Fifth International Conference on Systemic Lupus ErythematosusArticle, book review (Other scientific)
  • 63.
    Alarcón-Riquelme, Marta E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Nucleic acid by-products and chronic inflammation.2006In: Nat Genet, ISSN 1061-4036, Vol. 38, no 8, p. 866-7Article in journal (Other scientific)
  • 64.
    Alarcón-Riquelme, Marta E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Recent advances in the genetics of autoimmune diseases2007In: AUTOIMMUNITY, PT B: NOVEL APPLICATIONS OF BASIC RESEARCH / [ed] Gershwin ME, Shoenfeld Y, 2007, Vol. 1110, p. 1-9Conference paper (Refereed)
    Abstract [en]

    Autoimmune diseases in general are complex genetic diseases where genes and environment interact in unknown ways. In recent years technologies have advanced our knowledge and new genes are being identified very rapidly. We can expect that most genes of major importance for the various autoimmune diseases will be discovered in the coming 5 years. The real challenge comes when we try to understand the mechanisms through which these genes confer disease susceptibility and how the interaction with environment takes place such that clinical expression of the disease results.

  • 65.
    Alarcón-Riquelme, MArta E.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Studies on the effects of gamma irradiation on the lupus-prone strain (NZBxNZW)F11997In: International Conference on Immunopathology of mucous membranes and exocrine glandsArticle, book review (Other scientific)
  • 66.
    Alarcón-Riquelme, Marta E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    The genetics of shared autoimmunity.2005In: Autoimmunity, ISSN 0891-6934, Vol. 38, no 3, p. 205-8Article, book review (Other (popular scientific, debate etc.))
  • 67.
    Alarcón-Riquelme, Marta E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    The genetics of systemic lúpus erythematosus: The path ahead.2007In: Autoimmunity, ISSN 1607-842X, Vol. 40, no 8, p. 549-Article, review/survey (Other (popular scientific, debate etc.))
  • 68.
    Alarcón-Riquelme, ME
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Family studies in systemic lupus erythematosus2002In: Rheumatology, Vol. 41, p. 364Other (Other scientific)
  • 69.
    Alarcón-Riquelme, ME
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Alarcón-Segovia, D
    Factores Genéticos en la Patogenia del Lupus eritematoso sistemico2002Chapter in book (Other scientific)
  • 70. Alarcón-Segovia, D
    et al.
    Alarcón-Riquelme, Marta
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Etiopathogenesis of systemic lupus erythematosus1998Chapter in book (Other scientific)
  • 71. Alarcón-Segovia, Donato
    et al.
    Alarcón-Riquelme, Marta
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Shared autoimmunity: The concept and introduction.2005Other (Other scientific)
  • 72. Alarcón-Segovia, Donato
    et al.
    Alarcón-Riquelme, Marta E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Cardiel, Mario H
    Caeiro, Francisco
    Massardo, Loreto
    Villa, Antonio R
    Pons-Estel, Bernardo A
    Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort.2005In: Arthritis Rheum, ISSN 0004-3591, Vol. 52, no 4, p. 1138-47Article in journal (Refereed)
  • 73. Albert, Frank W.
    et al.
    Carlborg, Örjan
    SLU.
    Plyusnina, Irina
    Besnier, Francois
    Hedwig, Daniela
    Lautenschläger, Susann
    Lorenz, Doreen
    McIntosh, Jenny
    Neumann, Christof
    Richter, Henning
    Zeising, Claudia
    Kozhemyakina, Rimma
    Shchepina, Olesya
    Kratzsch, Jürgen
    Trut, Lyudmila
    Teupser, Daniel
    Thiery, Joachim
    Schöneberg, Torsten
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Pääbo, Svante
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Genetic architecture of tameness in a rat model of animal domestication2009In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 182, no 2, p. 541-554Article in journal (Refereed)
    Abstract [en]

    A common feature of domestic animals is tameness - i.e., they tolerate and are unafraid of human presence and handling. To gain insight into the genetic basis of tameness and aggression, we studied an intercross between two lines of rats (Rattus norvegicus) selected over >60 generations for increased tameness and increased aggression against humans, respectively. We measured 45 traits, including tameness and aggression, anxiety-related traits, organ weights, and levels of serum components in >700 rats from an intercross population. Using 201 genetic markers, we identified two significant quantitative trait loci (QTL) for tameness. These loci overlap with QTL for adrenal gland weight and for anxiety-related traits and are part of a five-locus epistatic network influencing tameness. An additional QTL influences the occurrence of white coat spots, but shows no significant effect on tameness. The loci described here are important starting points for finding the genes that cause tameness in these rats and potentially in domestic animals in general.

  • 74. Albert, Frank W.
    et al.
    Shchepina, Olesya
    Winter, Christine
    Roempler, Holger
    Teupser, Daniel
    Palme, Rupert
    Ceglarek, Uta
    Kratzsch, Juergen
    Sohr, Reinhard
    Trut, Lyudmila N.
    Thiery, Joachim
    Morgenstern, Rudolf
    Plyusnina, Irina Z.
    Schöneberg, Torsten
    Pääbo, Svante
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Phenotypic differences in behavior, physiology and neurochemistry between rats selected for tameness and for defensive aggression towards humans2008In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 53, no 3, p. 413-421Article in journal (Refereed)
    Abstract [en]

    To better understand the biology of tameness, i.e. tolerance of human presence and handling, we analyzed two lines of wild-derived rats (Rattus norvegicus) artificially selected for tameness and defensive aggression towards humans. In response to a gloved human hand, tame rats tolerated handling, whereas aggressive rats attacked. Cross-fostering showed that these behavioral differences are not caused by postnatal maternal effects. Tame rats were more active and explorative and exhibited fewer anxiety-related behaviors. They also had smaller adrenal glands, larger spleens and lower levels of serum corticosterone. Blood glucose levels were lower in tame rats, whereas the concentrations of nine amino acids were higher. In the brain, tame rats had lower serotonin and higher taurine levels than aggressive rats. Our findings reinforce the notion that tameness is correlated with differences in stress response and will facilitate future efforts to uncover the genetic basis for animal tameness.

  • 75. Albuquerque, Joaquim F. S.
    et al.
    Ferra, Maria A.
    Portela-Gomes, Guida M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Adaptive changes of the enterochromaffin and gastrin cells in the rat gastrointestinal tract following subtotal colectomy2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 8, p. 963-968Article in journal (Refereed)
    Abstract [en]

    Objective. Colectomized patients often have diarrhoea and increased gastric acid secretion. Although serotonin influences gastrointestinal (GI) motility and secretion, GI serotonin-producing enterochromaffin (EC) cells have not been investigated after colectomy, nor have the antral gastrin cells. The aim of this experimental study was to investigate the GI tract in rats 8 weeks after subtotal colectomy, with particular emphasis on the frequency and distribution of EC and gastrin cells. Material and methods. Immunohistochemical techniques were used to identify the two endocrine cell types. Results. The colectomized animals had diarrhoea. Body-weight was lower and the small intestine shorter in the colectomized animals compared with sham-operated and untreated controls. In the two surgically treated groups, the antral mucosa was thinner and the small intestinal mucosa was thicker compared with that of the untreated rats, whereas the thickness of the rectum of the colectomized rats was increased compared with that of the control groups. In the colectomized animals, the number of EC cells was increased in the small intestine and rectum, whereas the numbers of both EC and gastrin cells were decreased in the antrum. Conclusions. The results indicate that colectomy exerts a significant influence on the GI mucosa and on the endocrine cell systems studied. An increased number of EC cells can result in alterations in motility and secretion, which may be important in the pathogenesis of the diarrhoea that often occurs after colectomy.

  • 76. Alderborn, A
    et al.
    Anvret, M
    Gustavson, K-H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Hagenas, L
    Wadelius, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Achondroplasia in Sweden caused by a specific point mutation in FGFR3.1996In: Acta Paediatr., Vol. 85, p. 1506-Article in journal (Refereed)
  • 77. Alderborn, A
    et al.
    Anvret, M
    Gustavson, K-H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Hagenas, L
    Wadelius, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Arvsmassans vanligaste nymutation orsakar akondroplasi - kan nu diagnosticeras med DNA-analys.1997In: Läkartidningen, Vol. 94, p. 341-Article in journal (Other scientific)
  • 78.
    Alderborn, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Siegbahn, A
    Faculty of Medicine, Department of Medical Sciences.
    Wadelius, C
    Department of Genetics and Pathology.
    Venous thrombosis: factor V G1691A genotyping related to APC resistance as measured by 2 methods1997In: Eur J Haematol, Vol. 58, p. 229-Article in journal (Refereed)
  • 79.
    Alderborn, Anders
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Kamali, Masood
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Söderberg, Ola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Schlingemann, Heidi
    Nilsson, Mats
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Landegren, Ulf
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    The hunt for cancer biomarkers: Proximity ligation – a new technology for ultra-sensitive protein analysis2006Other (Other (popular scientific, debate etc.))
  • 80.
    Alderborn, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sundström, Jens
    Soeria-Atmadja, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandberg, Martin
    Andersson, H. Christer
    Hammerling, Ulf
    Genetically modified plants for non-food or non-feed purposes: straightforward screening for their appearance in food and feed2010In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 48, no 2, p. 453-464Article in journal (Refereed)
    Abstract [en]

    Genetically modified (GM) plants aimed at producing food/feed are part of regular agriculture in many areas of the World. Commodity plants have also found application as bioreactors, designated non-food/non-feed GM (NFGM) plants, thereby making raw material for further refinement to industrial, diagnostic or pharmaceutical preparations. Many among them may pose health challenge to consumers or livestock animals, if occurring in food/feed. NFGM plants are typically released into the environment, but are grown under special oversight and any among several containment practices, none of which provide full protection against accidental dispersal. Adventitious admixture with food or feed can occur either through distributional mismanagement or as a consequence of gene flow to plant relatives. To facilitate NFGM surveillance we propose a new mandatory tagging of essentially all such plants, prior to cultivation or marketing in the European Union. The suggested tag--Plant-Made Industrial or Pharmaceutical Products Tag (PMIP-T)--is envisaged to occur as a transgenic silent DNA identifier in host plants and designed to enable technically simple identification and characterisation of any NFGM. Implementation of PMIP-T would permit inexpensive, reliable and high-throughput screening for NFGM specifically. The paper outlines key NFGM prospects and challenges as well as the PMIP-T concept.

  • 81.
    Alemany Ripoll, Montserrat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Gustafsson, O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Siösteen, B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Olsson, Y.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    MR follow-up of small experimental intracranial haemorrhages from hyperacute to subacute phase2002In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 43, no 1, p. 2-9Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare pulse sequences in revealing intracranial bleeding from the hyperacute to subacute phase. MATERIAL AND METHODS: We injected 0.3-1 ml of autologous blood into the brain of 8 rabbits. MR imaging was performed immediately after haematoma creation and then at determined intervals up to 9-12 days. All images were analysed by two observers. After the last MR investigation, the brain was fixed in formalin. The last MR images were compared to the fixed brain sections and to the histologic findings. RESULTS: T2*-weighted GE sequences, both conventional spoiled and echoplanar sequences, revealed the intraparenchymal haematomas as hypointensities in all but 1 case, which was negative from the second day onward (a rabbit with 0.3 ml blood injected). The signal patterns remained unchanged during the follow-up. The haematoma sizes and shapes corresponded well to gross pathology. Blood in the cerebrospinal fluid (CSF) space was detected with T2*-weighted GE sequences in a great majority of the examinations during the first 2 days. The cases with the smallest injected volume of blood were negative. SE sequences were rather insensitive. The FLAIR sequence often revealed blood in CSF spaces but not in the brain. CONCLUSION: T2*-weighted GE sequences are capable of revealing very small intraparenchymal haemorrhages from the hyperacute to the subacute phase, and blood in CSF spaces during at least the first 2 days.

  • 82.
    Alemi, M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Andersson, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Sallstrom, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Wilander, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Rapid test for identification of a Human Papillomavirus 16 L83V E6 Variant.1999In: Diagn Mol Pathol, Vol. 8, p. 97-Article in journal (Refereed)
  • 83.
    Alemi, M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Lucas, SD
    Department of Surgical Sciences.
    Sallstrom, JF
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Bergholm, U
    Department of Surgical Sciences.
    Åkerström, Göran
    Department of Surgical Sciences.
    Wilander, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    A complex nine base pair deletion in RET exon 11 common in sporadic medullary thyroid carcinoma1997In: Oncogene, Vol. 14, p. 2041-Article in journal (Refereed)
  • 84.
    Alemi, Mansour
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Molecular biological techniques as a tool in diagnostic pathology: Applications in B-cell lymphoproliferative disease, medullary thyroid carcinoma and cervical carcinoma2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Identification of malignancy associated with mutations in gene sequences requires detection ofas little as a single base difference. A powerful technique in mutation detection is polymerasechain reaction (PCR) followed by single-strand conformational polymorphism (SSCP) andsequencing.

    The present investigation is focused on improving tests for the following diagnostic questions:(i) clonality in malignancy of lymphoid origin by developing simple laboratory methodsbased on PCR in which the monoclonal B-cell lineage can be distinguished from thepolyclonal, (ii) presence of mutations in RET proto-oncogene involved in sporadic medullarythyroid carcinoma (MTC), and (iii) development of a simple test which can distinguishbetween prototype human papillomavirus 16 (HPV16) and variant HPV16 containing a pointmutation at codon 83 of the E6 gene.

    The rearrangement of the immunoglobulin heavy chain gene can be used as a marker of B-celllineage and clonality. By using PCR with specific primers corresponding to the variable and joining regions, it is possible to detect the rearrangement of a small amount of clonal B-cells ina polyclonal background. This study has shown that the SSCP analysis of PCR fragmentsincreases the sensitivity and the specificity of the test.

    Oncogenic activation of the RET related to somatic missense mutations has been shown insporadic MTC. These mutations are believed to play an important role in the tumorigenesis ofMTC. By combining microdissection of tumor cells followed by PCR-SSCP, fragment sizeanalysis and sequencing, a small proportion of cells with mutation in a subpopulation of cellswithin a tumor can be detected. A variant of HPV 16 has previously been shown to be moreprevalent in invasive cervical carcinoma than in preinvasive lesions. In the present study asimple, rapid PCR-SSCP assay has been developed to identify women who are at increasedrisk of progression to invasive cervical carcinoma.

  • 85.
    Alemi, Mansour
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Lucas, Steven. D.
    Department of Surgical Sciences.
    Sallstrom, Jan. F.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Åkerström, Göran
    Department of Surgical Sciences.
    Wilander, Erik
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    A novel deletion in the RET proto-oncogen in sporadic medullary thyroid carcinoma1996In: Anticancer Res, Vol. 16, p. 2619-Article in journal (Refereed)
  • 86.
    Aleskog, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Larsson, R
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Hoglund, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Sundstrom, C
    Department of Genetics and Pathology.
    Kristensen, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Evaluation of purine and pyrimidine analogues in human tumor cells from patients with low-grade lymphoproliferative disorders using the FMCA1999In: Eur J Haematol, Vol. 62, p. 293-Article in journal (Refereed)
  • 87. Alexanderson, Camilla
    et al.
    Stener-Victorin, Elisabet
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Nilsson, Staffan
    Levin, Max
    Cajander, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Lönn, Lars
    Lönn, Malin
    Holmäng, Agneta
    A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats2010In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 122, no 1-3, p. 82-90Article in journal (Refereed)
    Abstract [en]

    Events during early life can affect reproductive and metabolic functions in adulthood. We evaluated the programming effects of a single early postnatal estradiol injection (within 3h after birth) in female rats. We assessed ovarian and parametrial adipose tissue morphology, evaluated gene expression related to follicular development and adipose tissue metabolism, and developed a non-invasive volumetric estimation of parametrial adipose tissue by magnetic resonance imaging. Estradiol reduced ovarian weight, increased antral follicle size and number of atretic antral follicles, and decreased theca interna thickness in atretic antral follicles. Adult estradiol-injected rats also had malformed vaginal openings and lacked corpora lutea, confirming anovulation. Estradiol markedly reduced parametrial adipose tissue mass. Adipocyte size was unchanged, suggesting reduced adipocyte number. Parametrial adipose tissue lipoprotein lipase activity was increased. In ovaries, estradiol increased mRNA expression of adiponectin, complement component 3, estrogen receptor alpha, and glucose transporter 3 and 4; in parametrial adipose tissue, expression of complement component 3 was increased, expression of estrogen receptor alpha was decreased, and expression of leptin, lipoprotein lipase, and hormone-sensitive lipase was unaffected. These findings suggest that early postnatal estradiol exposure of female rats result in long-lasting effects on the ovary and parametrial adipose tissue at adult age.

  • 88. Alfonso, Julieta
    et al.
    Pollevick, Guido
    Castensson, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Jazin, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Frasch, Alberto
    Analysis of gene expression in the rat hippocampus using Real Time PCR reveals high inter-individual variation in mRNA expression levels2002In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 67, no 2, p. 225-34Article in journal (Refereed)
    Abstract [en]

    In mammals, gene transcription is a step subjected to tight regulation mechanisms. In fact, changes in mRNA levels in the central nervous system (CNS) can account for numerous phenotypic differences in brain function. We performed a high-resolution analysis of mRNA expression levels for 37 genes selected from a normal rat hippocampus cDNA library. mRNA amounts were quantified using a Real Time PCR SYBR Green assay. We found that, in general, individuals from an inbred rat population (n = 20) have shown 2-3 times differences in the basal level of expression of the genes analyzed. Up to several fold differences among individuals were observed for certain genes. These inter-individual differences were obtained after correction for the different amounts of mRNA in each sample. Power calculations were performed to determine the number of individuals required to detect reliable differences in expression levels between a control and an experimental group. These data indicated that, depending on the variability of the candidate gene selected, it was necessary to analyze from five to 135 individuals in each group to detect differences of 50% in the levels of mRNA expression between two groups investigated. The comparison of mRNA abundance from different genes revealed a wide range of expression levels for the 37 genes, showing a 26,000-fold difference between the highest and lowest expressed gene.

  • 89.
    Alfredsson, Jessica
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Molecular Studies of Mast Cell Migration and Apoptosis: Two Ways of Regulating Mast Cell Numbers at Sites of Inflammation2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Upon activation mast cells release numerous proinflammatory mediators. With this feature, mast cells play an important role in host defense against pathogens, and are involved in tissue remodeling and wound healing. However, in cases of excessive inflammation the effects of mast cells are detrimental. This is observed in allergy, asthma, rheumatoid arthritis, atherosclerosis, certain types of heart failure, and in several other chronic destructive inflammations. Mast cell numbers are typically increased at inflammatory sites. There they act both directly, as effector cells, and in a regulatory manner, secreting agents that recruit and activate other immune cells.

    The studies presented here investigated mechanisms regulating mast cell numbers at sites of inflammation, focusing on cell migration and regulation of survival/apoptosis. We report that SCF-induced mast cell migration requires p38 MAP kinase activity. Moreover, we found that SCF-mediated mast cell survival is regulated through downregulation of the proapoptotic Bcl-2 family member Bim, as well as through phoshorylation of Bim. SCF seems to control Bim protein levels via FOXO transcription factors, and to induce phosphorylation of Bim via the Mek/Erk and the PI3-kinase/Akt signaling pathways. Furthermore, mast cell death triggered by deprivation of SCF and/or IL-3 involves the Bim protein, as demonstrated using bim-/- mast cells. Additional studies revealed that IgE-receptor activation, which occurs in allergy, promotes both prosurvival and proapoptotic signaling events. This includes upregulation of Bim and the prosurvival Bcl-XL and A1, as well as phosphorylation of Akt, FOXO factors, GSK-3β, IκB-α, Bad, and Bim. The simultaneous stimulation of prosurvival and proapoptotic signaling events could be a way to fine-tune the fate of mast cells after IgE-receptor activation and degranulation.

    The new insights about mechanisms involved in mast cell migration and regulation of survival/apoptosis might prove useful for future efforts to design new drugs to be used for mast cell-associated diseases.

    List of papers
    1. Stem Cell Factor-Induced Migration of Mast Cells Requires p38 Mitogen-Activated Protein Kinase Activity
    Open this publication in new window or tab >>Stem Cell Factor-Induced Migration of Mast Cells Requires p38 Mitogen-Activated Protein Kinase Activity
    2001 In: Experimental Cell Research, Vol. 267, no 1, p. 144-151Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92671 (URN)
    Available from: 2005-03-11 Created: 2005-03-11Bibliographically approved
    2. Stem cell factor promotes mast cell survival via inactivation of FOXO3a mediated transcriptional induction and MEK regulated phosphorylation of the pro-apoptotic protein Bim
    Open this publication in new window or tab >>Stem cell factor promotes mast cell survival via inactivation of FOXO3a mediated transcriptional induction and MEK regulated phosphorylation of the pro-apoptotic protein Bim
    Show others...
    Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-92672 (URN)
    Available from: 2005-03-11 Created: 2005-03-11Bibliographically approved
    3. Porapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation
    Open this publication in new window or tab >>Porapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation
    Show others...
    2005 In: Cell Death and Differentiation, Vol. 12, no 2, p. 136-144Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92673 (URN)
    Available from: 2005-03-11 Created: 2005-03-11Bibliographically approved
    4. IgE-receptor activation of mast cells regulates phosphorylation and expression of forkhead and Bcl-2 family members
    Open this publication in new window or tab >>IgE-receptor activation of mast cells regulates phosphorylation and expression of forkhead and Bcl-2 family members
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-92674 (URN)
    Available from: 2005-03-11 Created: 2005-03-11 Last updated: 2010-01-13Bibliographically approved
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  • 90.
    Alfredsson, Jessica
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Möller, Christine
    Nilsson, Gunnar
    IgE-receptor activation of mast cells regulates phosphorylation and expression of forkhead and Bcl-2 family membersManuscript (Other academic)
  • 91.
    Alfredsson, Jessica
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Puthalakath, Hamsa
    Martin, Helene
    Strasser, Andreas
    Nilsson, Gunnar
    Porapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation2005In: Cell Death and Differentiation, Vol. 12, no 2, p. 136-144Article in journal (Refereed)
  • 92.
    Ali, Muhammad Akhtar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sjöblom, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Molecular pathways in tumor progression: from discovery to functional understanding2009In: Molecular bioSystems, ISSN 1742-206X, Vol. 5, no 9, p. 902-908Article, review/survey (Refereed)
    Abstract [en]

    The advent of large scale sequencing methods has enabled analyses of the protein-coding parts of cancer genomes to find the mutated genes that cause common human cancers. Unbiased mutation analyses of human tumors originating in the breast, colon, brain, and pancreas have revealed genomic landscapes composed of a few frequently mutated genes alongside a multitude of infrequently mutated genes. These analyses have revealed a stark heterogeneity in the compendium of mutated genes even among tumors of the same tissue origin, and provide evidence for a larger number of driver mutations during tumorigenesis than hitherto presumed. From the multitude of mutated genes, a limited number of central molecular pathways are emerging. Systems biology approaches will be increasingly important to identify and better define these core pathways. Downstream of genetic analyses, scalable methods for prediction and experimental determination of the phenotypes of mutant alleles and pathways will be instrumental for improved mechanistic understanding of cancer as well as future drug discovery efforts.

  • 93.
    Alimohammadi, Mohammad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Dubois, Noemie
    Sköldberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Hallgren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tradivel, Isabelle
    Hedstrand, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Haavik, Jan
    Husebye, Eystein
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Meloni, Antonella
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Vilattes, Bernard
    Kajosaari, Merja
    Egner, William
    Sargur, Ravishankar
    Amoura, Zahir
    Grimfeld, Alain
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    De Luca, Filippo
    Betterle, Corrado
    Perheentupa, Jaakko
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 11, p. 4396-4401Article in journal (Refereed)
    Abstract [en]

    Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.

  • 94. Allen, Hana Lango
    et al.
    Estrada, Karol
    Lettre, Guillaume
    Berndt, Sonja I.
    Weedon, Michael N.
    Rivadeneira, Fernando
    Willer, Cristen J.
    Jackson, Anne U.
    Vedantam, Sailaja
    Raychaudhuri, Soumya
    Ferreira, Teresa
    Wood, Andrew R.
    Weyant, Robert J.
    Segre, Ayellet V.
    Speliotes, Elizabeth K.
    Wheeler, Eleanor
    Soranzo, Nicole
    Park, Ju-Hyun
    Yang, Jian
    Gudbjartsson, Daniel
    Heard-Costa, Nancy L.
    Randall, Joshua C.
    Qi, Lu
    Smith, Albert Vernon
    Maegi, Reedik
    Pastinen, Tomi
    Liang, Liming
    Heid, Iris M.
    Luan, Jian'an
    Thorleifsson, Gudmar
    Winkler, Thomas W.
    Goddard, Michael E.
    Lo, Ken Sin
    Palmer, Cameron
    Workalemahu, Tsegaselassie
    Aulchenko, Yurii S.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Zillikens, M. Carola
    Feitosa, Mary F.
    Esko, Tonu
    Johnson, Toby
    Ketkar, Shamika
    Kraft, Peter
    Mangino, Massimo
    Prokopenko, Inga
    Absher, Devin
    Albrecht, Eva
    Ernst, Florian
    Glazer, Nicole L.
    Hayward, Caroline
    Hottenga, Jouke-Jan
    Jacobs, Kevin B.
    Knowles, Joshua W.
    Kutalik, Zoltan
    Monda, Keri L.
    Polasek, Ozren
    Preuss, Michael
    Rayner, Nigel W.
    Robertson, Neil R.
    Steinthorsdottir, Valgerdur
    Tyrer, Jonathan P.
    Voight, Benjamin F.
    Wiklund, Fredrik
    Xu, Jianfeng
    Zhao, Jing Hua
    Nyholt, Dale R.
    Pellikka, Niina
    Perola, Markus
    Perry, John R. B.
    Surakka, Ida
    Tammesoo, Mari-Liis
    Altmaier, Elizabeth L.
    Amin, Najaf
    Aspelund, Thor
    Bhangale, Tushar
    Boucher, Gabrielle
    Chasman, Daniel I.
    Chen, Constance
    Coin, Lachlan
    Cooper, Matthew N.
    Dixon, Anna L.
    Gibson, Quince
    Grundberg, Elin
    Hao, Ke
    Junttila, M. Juhani
    Kaplan, Lee M.
    Kettunen, Johannes
    Koenig, Inke R.
    Kwan, Tony
    Lawrence, Robert W.
    Levinson, Douglas F.
    Lorentzon, Mattias
    McKnight, Barbara
    Morris, Andrew P.
    Mueller, Martina
    Ngwa, Julius Suh
    Purcell, Shaun
    Rafelt, Suzanne
    Salem, Rany M.
    Salvi, Erika
    Sanna, Serena
    Shi, Jianxin
    Sovio, Ulla
    Thompson, John R.
    Turchin, Michael C.
    Vandenput, Liesbeth
    Verlaan, Dominique J.
    Vitart, Veronique
    White, Charles C.
    Ziegler, Andreas
    Almgren, Peter
    Balmforth, Anthony J.
    Campbell, Harry
    Citterio, Lorena
    De Grandi, Alessandro
    Dominiczak, Anna
    Duan, Jubao
    Elliott, Paul
    Elosua, Roberto
    Eriksson, Johan G.
    Freimer, Nelson B.
    Geus, Eco J. C.
    Glorioso, Nicola
    Haiqing, Shen
    Hartikainen, Anna-Liisa
    Havulinna, Aki S.
    Hicks, Andrew A.
    Hui, Jennie
    Igl, Wilmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Illig, Thomas
    Jula, Antti
    Kajantie, Eero
    Kilpelaeinen, Tuomas O.
    Koiranen, Markku
    Kolcic, Ivana
    Koskinen, Seppo
    Kovacs, Peter
    Laitinen, Jaana
    Liu, Jianjun
    Lokki, Marja-Liisa
    Marusic, Ana
    Maschio, Andrea
    Meitinger, Thomas
    Mulas, Antonella
    Pare, Guillaume
    Parker, Alex N.
    Peden, John F.
    Petersmann, Astrid
    Pichler, Irene
    Pietilainen, Kirsi H.
    Pouta, Anneli
    Riddertrale, Martin
    Rotter, Jerome I.
    Sambrook, Jennifer G.
    Sanders, Alan R.
    Schmidt, Carsten Oliver
    Sinisalo, Juha
    Smit, Jan H.
    Stringham, Heather M.
    Walters, G. Bragi
    Widen, Elisabeth
    Wild, Sarah H.
    Willemsen, Gonneke
    Zagato, Laura
    Zgaga, Lina
    Zitting, Paavo
    Alavere, Helene
    Farrall, Martin
    McArdle, Wendy L.
    Nelis, Mari
    Peters, Marjolein J.
    Ripatti, Samuli
    vVan Meurs, Joyce B. J.
    Aben, Katja K.
    Ardlie, Kristin G.
    Beckmann, Jacques S.
    Beilby, John P.
    Bergman, Richard N.
    Bergmann, Sven
    Collins, Francis S.
    Cusi, Daniele
    den Heijer, Martin
    Eiriksdottir, Gudny
    Gejman, Pablo V.
    Hall, Alistair S.
    Hamsten, Anders
    Huikuri, Heikki V.
    Iribarren, Carlos
    Kahonen, Mika
    Kaprio, Jaakko
    Kathiresan, Sekar
    Kiemeney, Lambertus
    Kocher, Thomas
    Launer, Lenore J.
    Lehtimaki, Terho
    Melander, Olle
    Mosley, Tom H., Jr.
    Musk, Arthur W.
    Nieminen, Markku S.
    O'Donnell, Christopher J.
    Ohlsson, Claes
    Oostra, Ben
    Palmer, Lyle J.
    Raitakari, Olli
    Ridker, Paul M.
    Rioux, John D.
    Rissanen, Aila
    Rivolta, Carlo
    Schunkert, Heribert
    Shuldiner, Alan R.
    Siscovick, David S.
    Stumvoll, Michael
    Toenjes, Anke
    Tuomilehto, Jaakko
    van Ommen, Gert-Jan
    Viikari, Jorma
    Heath, Andrew C.
    Martin, Nicholas G.
    Montgomery, Grant W.
    Province, Michael A.
    Kayser, Manfred
    Arnold, Alice M.
    Atwood, Larry D.
    Boerwinkle, Eric
    Chanock, Stephen J.
    Deloukas, Panos
    Gieger, Christian
    Gronberg, Henrik
    Hall, Per
    Hattersley, Andrew T.
    Hengstenberg, Christian
    Hoffman, Wolfgang
    Lathrop, G. Mark
    Salomaa, Veikko
    Schreiber, Stefan
    Uda, Manuela
    Waterworth, Dawn
    Wright, Alan F.
    Assimes, Themistocles L.
    Barroso, Ines
    Hofman, Albert
    Mohlke, Karen L.
    Boomsma, Dorret I.
    Caulfield, Mark J.
    Cupples, L. Adrienne
    Erdmann, Jeanette
    Fox, Caroline S.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Harris, Tamara B.
    Hayes, Richard B.
    Jarvelin, Marjo-Ritta
    Mooser, Vincent
    Munroe, Patricia B.
    Ouwehand, Willem H.
    Penninx, Brenda W.
    Pramstaller, Peter P.
    Quertermous, Thomas
    Rudan, Igor
    Samani, Nilesh J.
    Spector, Timothy D.
    Voelzke, Henry
    Watkins, Hugh
    Wilson, James F.
    Groop, Leif C.
    Haritunians, Talin
    Hu, Frank B.
    Kaplan, Robert C.
    Metspalu, Andres
    North, Kari E.
    Schlessinger, David
    Wareham, Nicholas J.
    Hunter, David J.
    O'Connell, Jeffrey R.
    Strachan, David P.
    Schadt, H. -Erich
    Thorsteinsdottir, Unnur
    Peltonen, Leena
    Uitterlinden, Andre G.
    Visscher, Peter M.
    Chatterjee, Nilanjan
    Loos, Ruth J. F.
    Boehnke, Michael
    McCarthy, Mark I.
    Ingelsson, Erik
    Lindgren, Cecilia M.
    Abecasis, Goncalo R.
    Stefansson, Kari
    Frayling, Timothy M.
    Hirschhorn, Joel N.
    Hundreds of variants clustered in genomic loci and biological pathways affect human height2010In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 467, no 7317, p. 832-838Article in journal (Refereed)
    Abstract [en]

    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

  • 95.
    Allen, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Divne, Anna-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Universal tag arrays in forensic SNP analysis.2005In: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 297, p. 141-154Article in journal (Refereed)
    Abstract [en]

    Microarray-based single nucleotide polymorphism (SNP) genotyping enables simultaneous and rapid detection of a large number of markers and is thus an attractive method for forensic individual acid identification. This assay relies on a one-color detection system and minisequencing in solution before hybridization to universal tag arrays. The minisequencing reaction is based on incorporation of a fluorescent dideoxynucleotide to a primer containing a tag-sequence flanking the position to be interrogated. This one-color system detects C and T polymorphisms in separate reactions on multiple polymerase chain reaction targets with the fluorophore TAMRA coupled to the respective dideoxynucleotide. After incorporation, tagged primer sequences are hybridized through their complementary sequence on the array, and positive signals are detected by a confocal laser-scanner.

  • 96.
    Allen, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Liu, Limin
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    A comprehensive polymerase chain reaction-oligonucleotide typing system for the HLA class I A locus1994In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 40, no 1, p. 25-32Article in journal (Refereed)
    Abstract [en]

    A comprehensive system for genetic typing of the HLA class I A locus is described, based on PCR amplification and typing with nonradioactively labeled SSO probes. Exons 1-3 of the A locus are amplified and typing is performed with a set of 30 nonradioactively labeled oligonucleotide probes. This system resolves 34 of 39 known alleles and 561 (94%) of 595 possible genotypes. Among a sample of 354 individuals from Sweden and China, 97.5% of the genotypes were resolved. Probes were directed preferentially at replacement substitutions in foreign antigen-binding sites, in order to detect not only the known alleles but also new combinations of polymorphic motifs, indicative of previously unrecognized alleles. Three individuals were found with a new combination of polymorphic motifs, suggesting the presence of at least one previously undescribed allele in the populations sampled. This typing system is useful for disease association studies, tissue typing, and in forensic medicine.

  • 97.
    Allen, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Saldeen, T.
    Pettersson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Genetic typing of HLA class II genes in Swedish populations: application to forensic analysis1993In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 38, no 3, p. 554-70Article in journal (Refereed)
    Abstract [en]

    In an attempt to determine the value of DNA based typing of HLA class II loci to forensic analysis, allele and genotype frequencies at DQA1, DQB1, DPB1, and DRB1 were determined in samples from two Swedish populations using hybridization with sequence specific oligonucleotides to PCR amplified DNA. Significant allele frequency differences were observed at the DQB1 and DRB1 loci between the two populations, as well as between one of the Swedish and a Norwegian population. The average heterozygosity varies between 0.74 to 0.91 and the power of discrimination between 0.90 to 0.98, with the highest values obtained for the DRB1 locus. The probability of genotype identity by chance differs on average 2% between the populations. When applied to a paternity case with one parent deceased and a criminal case, typing of class II loci proved in both cases informative. Analyses of DR and DQ genes does not increase the power of discrimination, due to strong linkage, but offers through the reconstruction of putative haplotypes an internal control for the consistency of the typing results at several loci. Typing of the DRB1 and DPB1 loci was found to result in an approximate combined average probability of genotype identity by chance of one in a thousand.

  • 98.
    Allen, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sandberg-Wollheim, Magnhild
    Sjögren, Karin
    Erlich, Henry A.
    Petterson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Association of susceptibility to multiple sclerosis in Sweden with HLA class II DRB1 and DQB1 alleles1994In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 39, no 1, p. 41-8Article in journal (Refereed)
    Abstract [en]

    The association of MS with HLA class II alleles was studied by PCR-based typing of the DQA1, DQB1, DRB1, and DPB1 loci in 94 Swedish patients with relapses and remissions of the disease. The haplotype DRB1*1501-DQA1*0102-DQB1*0602 was found to be positively associated and three haplotypes were found to be negatively associated with MS. Linkage disequilibrium makes it difficult to assess whether DRB1 or DQB1 plays the primary role in the disease association, while the association with DPB1 and DQA1 appears to be secondary to that of DQB1 and DRB1. Two of the three haplotypes negatively associated with MS carry the DQB1*0301 allele. Also, the negatively associated DRB1*0401-DQA1*0301-DQB1*0301 haplotype differs from those with nonassociated DRB1*0401-DQA1*0301-DQB1*0302 haplotype only at DQB1. These results suggest that DQB1 alleles, as well as some DRB1 alleles, are involved in susceptibility and protection to MS. In searching for sequence motifs in the DR beta chain associated with MS susceptibility, all DRB1 alleles on haplotypes positively associated with MS, including the DRB1*1501, were found to encode a Val at position 86 of the DR beta chain. Also, DRB1 alleles that are negatively associated with MS all encode a Gly at position 86, suggesting that the residue at position 86 may be critical in conferring susceptibility and protection to MS. Finally, when the effect of the DRB1*1501 haplotype was removed there was no support for the hypothesis that MS is associated with a putative DQ-alpha beta heterodimer, encoded for by certain DQA1 and DQB1 alleles.

  • 99. Allikmets, R
    et al.
    Seddon, JM
    Bernstein, PS
    Hutchinson, A
    Atkinson, A
    Sharma, S
    Gerrard, B
    Li, W
    Metzker, ML
    Wadelius, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Caskey, CT
    Dean, M
    Petrukhin, K
    Evaluation of the Best disease gene in patients with age-related maculardegeneration and other maculopathies.1999In: Hum Genet, Vol. 104, p. 449-Article in journal (Refereed)
  • 100. Almroth, A
    et al.
    Ljung, G
    Eklund, T
    Nordgren, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Kalafatidis, D
    Ringqvist, I
    Nilsson, S
    Value of sextant biopsies in the assessment of local cure following external beam radiotherapy of prostatic adenocarcinoma.1998In: Scand J Urol Nephrol, Vol. 32, p. 111-Article in journal (Refereed)
1234567 51 - 100 of 3130
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