uu.seUppsala University Publications
Change search
Refine search result
1234 1 - 50 of 193
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1. 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.

  • 2.
    Alexander, Michelle
    et al.
    Univ York, York YO10 5DD, N Yorkshire, England.;Univ Aberdeen, Sch Geosci, Dept Archaeol, Aberdeen AB24 3UF, Scotland..
    Ho, Simon Y. W.
    Univ Sydney, Sch Biol Sci, Sydney, NSW 2006, Australia..
    Molak, Martyna
    Polish Acad Sci, Museum & Inst Zool, PL-00679 Warsaw, Poland..
    Barnett, Ross
    Palaeogen & Bioarchaeol Res Network, Res Lab Archaeol, Oxford OX1 3QY, England..
    Carlborg, Örjan
    Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Dorshorst, Ben
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Virginia Tech, Dept Anim & Poultry Sci, Blacksburg, VA 24061 USA..
    Honaker, Christa
    Virginia Tech, Dept Anim & Poultry Sci, Blacksburg, VA 24061 USA..
    Besnier, Francois
    Inst Marine Res, Sect Populat Genet, N-5024 Bergen, Norway..
    Wahlberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Dobney, Keith
    Univ Aberdeen, Sch Geosci, Dept Archaeol, Aberdeen AB24 3UF, Scotland..
    Siegel, Paul
    Virginia Tech, Dept Anim & Poultry Sci, Blacksburg, VA 24061 USA..
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, S-75007 Uppsala, Sweden..
    Larson, Greger
    Palaeogen & Bioarchaeol Res Network, Res Lab Archaeol, Oxford OX1 3QY, England..
    Mitogenomic analysis of a 50-generation chicken pedigree reveals a rapid rate of mitochondrial evolution and evidence for paternal mtDNA inheritance2015In: Biology Letters, ISSN 1744-9561, E-ISSN 1744-957X, Vol. 11, no 10, article id 20150561Article in journal (Refereed)
    Abstract [en]

    Mitochondrial genomes represent a valuable source of data for evolutionary research, but studies of their short-term evolution have typically been limited to invertebrates, humans and laboratory organisms. Here we present a detailed study of 12 mitochondrial genomes that span a total of 385 transmissions in a well-documented 50-generation pedigree in which two lineages of chickens were selected for low and high juvenile body weight. These data allowed us to test the hypothesis of time-dependent evolutionary rates and the assumption of strict maternal mitochondrial transmission, and to investigate the role of mitochondrial mutations in determining phenotype. The identification of a non-synonymous mutation in ND4L and a synonymous mutation in CYTB, both novel mutations in Gallus, allowed us to estimate a molecular rate of 3.13 x 10(-7) mutations/site/year (95% confidence interval 3.75 x 10(-8)-1.12 x 10(-6)). This is substantially higher than avian rate estimates based upon fossil calibrations. Ascertaining which of the two novel mutations was present in an additional 49 individuals also revealed an instance of paternal inheritance of mtDNA. Lastly, an association analysis demonstrated that neither of the point mutations was strongly associated with the phenotypic differences between the two selection lines. Together, these observations reveal the highly dynamic nature of mitochondrial evolution over short time periods.

  • 3.
    Ali, Muhammad Akhtar
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Younis, Shady
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Wallerman, Ola
    Gupta, Rajesh
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Andersson, Leif
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sjoblöm, Tobias
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 25, p. 7743-7748Article in journal (Refereed)
    Abstract [en]

    The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle-related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-beta, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.

  • 4.
    Almén, Markus Sällman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lamichhaney, Sangeet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Berglund, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Grant, B. Rosemary
    Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA..
    Grant, Peter R.
    Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA..
    Webster, Matthew T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden.;Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA..
    Adaptive radiation of Darwin's finches revisited using whole genome sequencing2016In: Bioessays, ISSN 0265-9247, E-ISSN 1521-1878, Vol. 38, no 1, p. 14-20Article in journal (Refereed)
    Abstract [en]

    We recently used genome sequencing to study the evolutionary history of the Darwin's finches. A prominent feature of our data was that different polymorphic sites in the genome tended to indicate different genetic relationships among these closely related species. Such patterns are expected in recently diverged genomes as a result of incomplete lineage sorting. However, we uncovered conclusive evidence that these patterns have also been influenced by interspecies hybridisation, a process that has likely played an important role in the radiation of Darwin's finches. A major discovery was that segregation of two haplotypes at the ALX1 locus underlies variation in beak shape among the Darwin's finches, and that differences between the two haplotypes in a 240 kb region in blunt and pointed beaked birds involve both coding and regulatory changes. As we review herein, the evolution of such adaptive haplotypes comprising multiple causal changes appears to be an important mechanism contributing to the evolution of biodiversity.

  • 5. Alvarez-Castro, José M
    et al.
    Le Rouzic, Arnaud
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Siegel, Paul B
    Carlborg, Örjan
    Modelling of genetic interactions improves prediction of hybrid patterns: a case study in domestic fowl2012In: Genetical Research, ISSN 0016-6723, E-ISSN 1469-5073, Vol. 94, no 5, p. 255-266Article in journal (Refereed)
    Abstract [en]

    Summary A major challenge in complex trait genetics is to unravel how multiple loci and environmental factors together cause phenotypic diversity. Both first (F1) and second (F2) generation hybrids often display phenotypes that deviate from what is expected under intermediate inheritance. We have here studied two chicken F2 populations generated by crossing divergent chicken lines to assess how epistatic loci, identified in earlier quantitative trait locus (QTL) studies, contribute to hybrid deviations from the mid-parent phenotype. Empirical evidence suggests that the average phenotypes of the intercross birds tend to be lower than the midpoint between the parental means in both crosses. Our results confirm that epistatic interactions, despite a relatively small contribution to the phenotypic variance, play an important role in the deviation of hybrid phenotypes from the mid-parent values (i.e. multi-locus hybrid genotypes lead to lower rather than higher body weights). To a lesser extent, dominance also appears to contribute to the mid-parent deviation, at least in one of the crosses. This observation coincides with the hypothesis that hybridization tends to break up co-adapted gene complexes, i.e. generate Bateson-Dobzhansky-Muller incompatibilities.

  • 6.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Domestic Animals: A Treasure Trove for Comparative Genomics2007In: Comparative Genomics: Basic and Applied Research / [ed] James R. Brown, Boca Raton: Taylor & Francis Group , 2007, , p. 22p. 341-362Chapter in book (Other academic)
  • 7.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden.;Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA..
    Domestic animals as models for biomedical research2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 1-11Article, review/survey (Refereed)
    Abstract [en]

    Domestic animals are unique models for biomedical research due to their long history (thousands of years) of strong phenotypic selection. This process has enriched for novel mutations that have contributed to phenotype evolution in domestic animals. The characterization of such mutations provides insights in gene function and biological mechanisms. This review summarizes genetic dissection of about 50 genetic variants affecting pigmentation, behaviour, metabolic regulation, and the pattern of locomotion. The variants are controlled by mutations in about 30 different genes, and for 10 of these our group was the first to report an association between the gene and a phenotype. Almost half of the reported mutations occur in non-coding sequences, suggesting that this is the most common type of polymorphism underlying phenotypic variation since this is a biased list where the proportion of coding mutations are inflated as they are easier to find. The review documents that structural changes (duplications, deletions, and inversions) have contributed significantly to the evolution of phenotypic diversity in domestic animals. Finally, we describe five examples of evolution of alleles, which means that alleles have evolved by the accumulation of several consecutive mutations affecting the function of the same gene.

  • 8.
    Andersson, Leif
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Farm animals2005In: Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics, John Wiley & Sons Ltd. Chichester , 2005, p. 1171-1183Chapter in book (Other scientific)
  • 9.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Genome-wide association analysis in domestic animals: a powerful approach for genetic dissection of trait loci2009In: Genetica, ISSN 0016-6707, E-ISSN 1573-6857, Vol. 136, no 2, p. 341-349Article in journal (Refereed)
    Abstract [en]

    Domestic animals have a sufficiently old history (thousands of generations) to allow evolution of phenotypes, but also a sufficiently young history (approximately 10,000 years) to allow powerful genetic dissection of phenotypic diversity. Domestic animals are therefore a unique resource for exploring genotype-phenotype relationships. Quantitative Trait Locus (QTL) mapping has been very successful in domestic animals but the identification of Quantitative Trait Mutations (QTMs) has been hard although a few prominent success histories have been reported. Genome-wide association analysis is now emerging as a powerful method for high-resolution mapping of loci controlling phenotypic traits in domestic animals. In two recent proof-of-principle studies we have used this approach to identify the mutations underlying two monogenic trait loci in dogs, white spotting and the hair ridge in Ridgeback dogs. In each case, we used only about 10 cases and 10 controls and mapped the locus to a region of about one mega base pair. In both cases the underlying mutations were non-coding underscoring the significance of regulatory mutations as a source for phenotypic diversity. Furthermore, we were able to shed light on the evolution of the allelic series at the white spotting (S) locus in dogs which encodes the microphthalmia-associated transcription factor (MITF). Our data showed that the three variant alleles described at this locus (Irish spotting, piebald and extreme white) do not represent three independent mutations but rather different combinations of a set of regulatory mutations affecting MITF expression. This is an excellent illustration of how the characterization of alleles selected during animal domestication contributes to an improved understanding of genotype-phenotype relationships.

  • 10.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    How selective sweeps in domestic animals provide new insight into biological mechanisms2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 271, no 1, p. 1-14Article, review/survey (Refereed)
    Abstract [en]

    Genetic studies of domestic animals are of general interest because there is more phenotypic diversity to explore in these species than in any experimental organism. Some mutations with favourable phenotypic effects have been highly enriched and gone through selective sweeps during the process of domestication and selective breeding. Three such selective sweeps are described in this review. All three mutations are intronic and constitute cis-acting regulatory mutations. Two of the mutations constitute structural changes (one duplication and one copy number expansion). These examples illustrate a general trend that noncoding mutations and structural changes have both contributed significantly to the evolution of phenotypic diversity in domestic animals. How the molecular characterization of trait loci in domestic animals can provide new basic knowledge of relevance for human medicine is discussed.

  • 11.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Melanocortin Receptor Variants with Phenotypic Effects in Horse, Pig and Chicken2003In: The melanocortin system / [ed] Cone, Roger D, New York: New York Academy of Sciences , 2003, Vol. 994, p. 313-318Conference paper (Other academic)
    Abstract [en]

    The melanocortin system is of considerable interest in domestic animals because their energy metabolism and pigmentation have been under strong selection. This article reviews our work on MC1R variants in horse, pig, and chicken, as well as a study on MC4R polymorphism in the pig. The chestnut coat color in horses is caused by an MC1R missense mutation (S83F). In the pig, we have described seven MC1R alleles controlling four different coat color phenotypes (wild type, dominant black, black spotting, and recessive red). The most interesting allele is the one causing black spotting because it carries two causative mutations, a frameshift and a missense mutation. The frameshift mutation is somatically unstable, and the black spots reflect somatic reversion events restoring the reading frame. Classic genetics have established eight alleles at the Extended black locus in chicken, which is assumed to correspond to the Extension locus in mammals. We have analyzed the co-segregation of alleles at MC1R and Extended black using a red jungle fowl × White Leghorn intercross and provide compelling evidence that these loci are identical. A previous study indicated that a missense mutation (D298N) in pig MC4R has an effect on fatness, growth, and feed intake. We could not confirm this association using an intercross between the wild boar and Large White domestic pigs, but it is possible that our F2 generation was too small to detect the rather modest effect reported for this polymorphism

  • 12.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Molecular consequences of animal breeding2013In: Current Opinion in Genetics and Development, ISSN 0959-437X, E-ISSN 1879-0380, Vol. 23, no 3, p. 295-301Article in journal (Refereed)
    Abstract [en]

    The phenotypic diversity in domestic animals provides a unique opportunity to study genotype-phenotype relationships. The identification of causal mutations provides an insight into what types of mutations have contributed to phenotypic evolution in domestic animals. Whole genome sequencing has revealed that fixation of null alleles that inactivate genes, which are essential under natural conditions but disadvantageous on the farm, has not been a common mechanism for genetic adaptation in domestic animals. Numerous examples have been revealed where structural changes cause specific phenotypic effects by altering transcriptional regulation. An emerging feature is also the evolution of alleles by the accumulation of several consecutive mutations which affect gene function.

  • 13.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Studying phenotypic evolution in domestic animals: a walk in the footsteps of Charles Darwin.2009In: Cold Spring Harbor Symposia on Quantitative Biology, ISSN 0091-7451, E-ISSN 1943-4456, Vol. 74, p. 319-25Article in journal (Refereed)
    Abstract [en]

    Charles Darwin used domesticated plants and animals as proof of principle for his theory on phenotypic evolution by means of natural selection. Inspired by Darwin's work, we developed an intercross between the wild boar and domestic pigs to study the genetic basis for phenotypic changes during domestication. The difference in coat color is controlled by two major loci. Dominant white color is due to two consecutive mutations in the KIT gene: a 450-kb duplication and a splice mutation. Black spotting is caused by the combined effect of two mutations in MC1R: a missense mutation for dominant black color and a 2-bp insertion leading to a frameshift. A major discovery made using this pedigree is the identification of a single-nucleotide substitution in intron 3 of the gene for insulin-like growth factor 2 (IGF2) that is underlying a quantitative trait locus affecting muscle growth, size of the heart, and fat deposition. The mutation disrupts the interaction with a repressor and leads to threefold increased IGF2 expression in postnatal muscle. In a recent study, we have identified the IGF2 repressor, and this previously unknown protein, named ZBED6, is specific for placental mammals and derived from a domesticated DNA transposon.

  • 14.
    Andersson, Leif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hjälm, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Jiang, Lin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindroth, Anders M
    Markljung, Ellen
    Nyström, Anna-Maja
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sundström, Elisabeth
    ZBED6: the birth of a new transcription factor in the common ancestor of placental mammals2010In: Transcription, ISSN 2154-1272, Vol. 1, no 3, p. 144-148Article in journal (Refereed)
    Abstract [en]

    A DNA transposon integrated into -the genome of a primitive mammal some 200 million years ago and, millions of years later, it evolved an essential function in the common ancestor of all placental mammals. This protein, now named ZBED6, was recently discovered because a mutation disrupting one of its binding sites, in an intron of the IGF2 gene, makes pigs grow more muscle. These findings have revealed a new mechanism for regulating muscle growth as well as a novel transcription factor that appears to be of major importance for transcriptional regulation in placental mammals.

  • 15.
    Andersson, Leif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Swedish University of Agricultural Sciences.
    Archibald, Alan L.
    Bottema, Cynthia D.
    Brauning, Rudiger
    Burgess, Shane C.
    Burt, Dave W.
    Casas, Eduardo
    Cheng, Hans H.
    Clarke, Laura
    Couldrey, Christine
    Dalrymple, Brian P.
    Elsik, Christine G.
    Foissac, Sylvain
    Giuffra, Elisabetta
    Groenen, Martien A.
    Hayes, Ben J.
    Huang, LuSheng S.
    Khatib, Hassan
    Kijas, James W.
    Kim, Heebal
    Lunney, Joan K.
    McCarthy, Fiona M.
    McEwan, John C.
    Moore, Stephen
    Nanduri, Bindu
    Notredame, Cedric
    Palti, Yniv
    Plastow, Graham S.
    Reecy, James M.
    Rohrer, Gary A.
    Sarropoulou, Elena
    Schmidt, Carl J.
    Silverstein, Jeffrey
    Tellam, Ross L.
    Tixier-Boichard, Michele
    Tosser-Klopp, Gwenola
    Tuggle, Christopher K.
    Vilkki, Johanna
    White, Stephen N.
    Zhao, Shuhong
    Zhou, Huaijun
    Coordinated international action to accelerate genome-to-phenome with FAANG, the Functional Annotation of Animal Genomes project2015In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 16Article in journal (Refereed)
    Abstract [en]

    We describe the organization of a nascent international effort, the Functional Annotation of Animal Genomes (FAANG) project, whose aim is to produce comprehensive maps of functional elements in the genomes of domesticated animal species.

  • 16.
    Andersson, Leif
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Georges, Michel
    Domestic-animal genomics: deciphering the genetics of complex traits.2004In: Nat Rev Genet, ISSN 1471-0056, Vol. 5, no 3, p. 202-12Article in journal (Refereed)
  • 17.
    Andersson, Leif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sundström, Elisabeth
    Institutionen för husdjursgenetik, SLU.
    Den vita hästens gåta löst2008In: Forskning & Framsteg, ISSN 0744-08, no 8, p. 40-43Article in journal (Other (popular science, discussion, etc.))
  • 18. Andersson, Lisa S.
    et al.
    Larhammar, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Memic, Fatima
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Wootz, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Schwochow, Doreen
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Patra, Kalicharan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Arnason, Thorvaldur
    Wellbring, Lisbeth
    Hjälm, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Imsland, Freyja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Petersen, Jessica L.
    McCue, Molly E.
    Mickelson, James R.
    Cothran, Gus
    Ahituv, Nadav
    Roepstorff, Lars
    Mikko, Sofia
    Vallstedt, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Lindgren, Gabriella
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kullander, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 488, no 7413, p. 642-646Article in journal (Refereed)
    Abstract [en]

    Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement(1). These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles(2). Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.

  • 19.
    Baranowska, Izabella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Jäderlund, Karin Hultin
    Nennesmo, Inger
    Holmqvist, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Heidrich, Nadja
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Larsson, Nils-Göran
    Andersson, Göran
    Wagner, Gerhart E. H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Hedhammar, Åke
    Wibom, Rolf
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sensory ataxic neuropathy in golden retriever dogs is caused by a deletion in the mitochondrial tRNATyr gene2009In: PLoS Genetics, ISSN 1553-7390, Vol. 5, no 5, p. e1000499-Article in journal (Refereed)
    Abstract [en]

    Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNA(Tyr) gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0-11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNA(Tyr) had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNA(Tyr) gene is the causative mutation for SAN.

  • 20. Barnes, Brian R
    et al.
    Glund, Stephan
    Long, Yun Chau
    Hjälm, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Zierath, Juleen R
    5'-AMP-activated protein kinase regulates skeletal muscle glycogen content and ergogenics2005In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 19, no 7, p. 773-779Article in journal (Refereed)
    Abstract [en]

    5'-AMP-activated protein kinase (AMPK) activity is increased during exercise in an intensity- and glycogen-dependent manner. We previously reported that a mutation in the AMPK3 subunit (Prkag3225Q) increases AMPK activity and skeletal muscle glycogen content. Transfection experiments revealed the R225Q mutation is associated with high basal AMPK activity and diminished AMP dependence. Thus, the R225Q mutation can be considered a loss-of-function mutation that abolished allosteric regulation by AMP/ATP, causing increased basal AMPK activity. We used AMPK3 transgenic (Tg-Prkag3225Q) and knockout (Prkag3-/-) mice to determine the relationship between AMPK activity, glycogen content, and ergogenics (ability to perform work) in isolated extensor digitorum longus skeletal muscle after contractions induced by electrical stimulation. Contraction-induced AMPK activity was inversely coupled to glycogen content in wild-type and Tg-Prkag3225Q mice, but not in Prkag3-/- mice, highlighting a partial feedback control of glycogen on contraction-induced AMPK activity in the presence of a functional AMPK3 isoform. Skeletal muscle glycogen content was positively correlated to work performance, regardless of genotype. Thus, chronic activation of AMPK by the Prkag3225Q mutation directly influences skeletal muscle ergogenics by enhancing glycogen content. In conclusion, functional studies of the AMPK3 isoform further support the close connection between glycogen content and exercise performance in skeletal muscle.

  • 21. Barnes, Brian R
    et al.
    Long, Yun Chau
    Steiler, Tatiana L
    Leng, Ying
    Galuska, Dana
    Wojtaszewski, Jörgen F P
    Andersson, Leif
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Zierath, Juleen R
    Changes in Exercise-Induced Gene Expression in 5'-AMP-Activated Protein Kinase {gamma}3-Null and {gamma}3 R225Q Transgenic Mice.2005In: Diabetes, ISSN 0012-1797, Vol. 54, no 12, p. 3484-9Article in journal (Refereed)
  • 22. Barnes, Brian R
    et al.
    Marklund, Stefan
    Steiler, Tatiana L
    Walter, Mark
    Hjälm, Göran
    Amarger, Valerie
    Mahlapuu, Margit
    Leng, Ying
    Johansson, Carina
    Galuska, Dana
    Lindgren, Kerstin
    Åbrink, Magnus
    Stapleton, David
    Zierath, Juleen R
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The 5'-AMP-activated protein kinase gamma3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle2004In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 279, no 37, p. 38441-38447Article in journal (Refereed)
    Abstract [en]

    5'-AMP-activated protein kinase (AMPK) is a metabolic stress sensor present in all eukaryotes. A dominant missense mutation (R225Q) in pig PRKAG3, encoding the muscle-specific gamma3 isoform, causes a marked increase in glycogen content. To determine the functional role of the AMPK gamma3 isoform, we generated transgenic mice with skeletal muscle-specific expression of wild type or mutant (225Q) mouse gamma3 as well as Prkag3 knockout mice. Glycogen resynthesis after exercise was impaired in AMPK gamma3 knock-out mice and markedly enhanced in transgenic mutant mice. An AMPK activator failed to increase skeletal muscle glucose uptake in AMPK gamma3 knock-out mice, whereas contraction effects were preserved. When placed on a high fat diet, transgenic mutant mice but not knock-out mice were protected against excessive triglyceride accumulation and insulin resistance in skeletal muscle. Transfection experiments reveal the R225Q mutation is associated with higher basal AMPK activity and diminished AMP dependence. Our results validate the muscle-specific AMPK gamma3 isoform as a therapeutic target for prevention and treatment of insulin resistance.

  • 23. Barsh, Gregory S.
    et al.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Evolutionary genomics: Detecting selection2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 495, no 7441, p. 325-326Article in journal (Other academic)
  • 24.
    Berg, Florian
    et al.
    University of Bergen, Department of Biology, Bergen; Institute of Marine Research (IMR), Nordnes, Bergen.
    Almeland, Oda W.
    University of Bergen, Department of Biology, Bergen.
    Skadal, Julie
    University of Bergen, Department of Biology, Bergen.
    Slotte, Aril
    Institute of Marine Research (IMR), Nordnes, Bergen.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics, Uppsala; Texas A&M University, Department of Veterinary Integrative Biosciences, College Station, Texas.
    Folkvord, Arild
    University of Bergen, Department of Biology, Bergen; Institute of Marine Research (IMR), Nordnes, Bergen.
    Genetic factors have a major effect on growth, number of vertebrae and otolith shape in Atlantic herring (Clupea harengus)2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 1, article id e0190995Article in journal (Refereed)
    Abstract [en]

    Atlantic herring, Clupea harengus, have complex population structures. Mixing of populations is known, but the extent of connectivity is still unclear. Phenotypic plasticity results in divergent phenotypes in response to environmental factors. A marked salinity gradient occurs from Atlantic Ocean (salinity 35) into the Baltic Sea (salinity range 2–12). Herring from both habitats display phenotypic and genetic variability. To explore how genetic factors and salinity influence phenotypic traits like growth, number of vertebrae and otolith shape an experimental population consisting of Atlantic purebreds and Atlantic/Baltic F1 hybrids were incubated and co-reared at two different salinities, 16 and 35, for three years. The F1-generation was repeatedly sampled to evaluate temporal variation. A von Bertalanffy growth model indicated that reared Atlantic purebreds had a higher maximum length (26.2 cm) than Atlantic/Baltic hybrids (24.8 cm) at salinity 35, but not at salinity 16 (25.0 and 24.8 cm, respectively). In contrast, Atlantic/Baltic hybrids achieved larger size-at-age than the wild caught Baltic parental group. Mean vertebral counts and otolith aspect ratios were higher for reared Atlantic purebreds than Atlantic/Baltic hybrids, consistent with the differences between parental groups. There were no significant differences in vertebral counts and otolith aspect ratios between herring with the same genotype but raised in different salinities. A Canonical Analysis of Principal Coordinates was applied to analyze the variation in wavelet coefficients that described otolith shape. The first discriminating axis identified the differences between Atlantic purebreds and Atlantic/Baltic hybrids, while the second axis represented salinity differences. Assigning otoliths based on genetic groups (Atlantic purebreds vs. Atlantic/Baltic hybrids) yielded higher classification success (~90%) than based on salinities (16 vs. 35; ~60%). Our results demonstrate that otolith shape and vertebral counts have a significant genetic component and are therefore useful for studies on population dynamics and connectivity.

  • 25.
    Berg, Frida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bourneuf, Emmanuelle
    Marklund, Stefan
    Andersson, Leif
    Further characterization of the FAT1 locus on pig chromosome 4 – evidence for two quantitative trait loci in the FAT1 regionManuscript (Other academic)
  • 26.
    Berg, Frida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gustafson, Ulla
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: A genetic explanation for poor thermoregulation in piglets2006In: PLoS Genetics, ISSN 1553-7390, Vol. 2, no 8, p. 1178-1181Article in journal (Refereed)
    Abstract [en]

    Piglets appear to lack brown adipose tissue, a specific type of fat that is essential for nonshivering thermogenesis in mammals, and they rely on shivering as the main mechanism for thermoregulation. Here we provide a genetic explanation for the poor thermoregulation in pigs as we demonstrate that the gene for uncoupling protein 1 (UCP1) was disrupted in the pig lineage. UCP1 is exclusively expressed in brown adipose tissue and plays a crucial role for thermogenesis by uncoupling oxidative phosphorylation. We used long-range PCR and genome walking to determine the complete genome sequence of pig UCP1. An alignment with human UCP1 revealed that exons 3 to 5 were eliminated by a deletion in the pig sequence. The presence of this deletion was confirmed in all tested domestic pigs, as well as in European wild boars, Bornean bearded pigs, wart hogs, and red river hogs. Three additional disrupting mutations were detected in the remaining exons. Furthermore, the rate of nonsynonymous substitutions was clearly elevated in the pig sequence compared with the corresponding sequences in humans, cattle, and mice, and we used this increased rate to estimate that UCP1 was disrupted about 20 million years ago.

  • 27.
    Berg, Frida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Stern, Susanne
    Andersson, Kjell
    Andersson, Leif
    Moller, Maria
    Refined localization of the FAT1 quantitative trait locus on pig chromosome 4 by marker-assisted backcrossing2006In: BMC Genet, Vol. 7, p. 17-Article in journal (Refereed)
  • 28.
    Berg, Frida
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Stern, Susanne
    Andersson, Kjell
    Andersson, Leif
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Moller, Maria
    Refined localization of the FAT1 quantitative trait locus on pig chromosome 4 by marker-assisted backcrossing.2006In: BMC Genet, ISSN 1471-2156, Vol. 7, p. 17-Article in journal (Other scientific)
  • 29.
    Besnier, Francois
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Wahlberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Rönnegård, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Ek, Weronica
    Swedish University of Agricultural Sciences .
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Siegel, Paul
    virginia polytechnic institute and state university.
    Carlborg, Örjan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Fine mapping and replication of QTL in outbred chicken advanced intercross lines2011In: Genetics Selection Evolution, ISSN 0999-193X, E-ISSN 1297-9686, Vol. 43, p. 3-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature.

    METHODS: We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight.

    RESULTS: Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL.

    CONCLUSIONS: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.

     

  • 30.
    Boije, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Harun-Or-Rashid, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Lee, Yu-Jen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Imsland, Freyja
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bruneau, Nicolas
    Vieaud, Agathe
    Gourichon, David
    Tixier-Boichard, Michèle
    Bed’hom, Bertrand
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hallböök, Finn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Sonic Hedgehog-Signalling Patterns the Developing Chicken Comb as Revealed by Exploration of the Pea-comb Mutation2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e50890-Article in journal (Refereed)
    Abstract [en]

    The genetic basis and mechanisms behind the morphological variation observed throughout the animal kingdom is stillrelatively unknown. In the present work we have focused on the establishment of the chicken comb-morphology byexploring the Pea-comb mutant. The wild-type single-comb is reduced in size and distorted in the Pea-comb mutant. Peacombis formed by a lateral expansion of the central comb anlage into three ridges and is caused by a mutation in SOX5,which induces ectopic expression of the SOX5 transcription factor in mesenchyme under the developing comb. Analysis ofdifferential gene expression identified decreased Sonic hedgehog (SHH) receptor expression in Pea-comb mesenchyme. Byexperimentally blocking SHH with cyclopamine, the wild-type single-comb was transformed into a Pea-comb-likephenotype. The results show that the patterning of the chicken comb is under the control of SHH and suggest that ectopicSOX5 expression in the Pea-comb change the response of mesenchyme to SHH signalling with altered combmorphogenesis as a result. A role for the mesenchyme during comb morphogenesis is further supported by the recentfinding that another comb-mutant (Rose-comb), is caused by ectopic expression of a transcription factor in combmesenchyme. The present study does not only give knowledge about how the chicken comb is formed, it also adds to ourunderstanding how mutations or genetic polymorphisms may contribute to inherited variations in the human face.

  • 31.
    Bornelöv, Susanne
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Cambridge, Wellcome Trust Med Res Council Stem Cell Inst, Cambridge CB2 1QR, England..
    Seroussi, Eyal
    Agr Res Org, Volcani Ctr, Rishon Leziyyon, Israel..
    Yosefi, Sara
    Agr Res Org, Volcani Ctr, Rishon Leziyyon, Israel..
    Pendavis, Ken
    Univ Arizona, Coll Agr & Life Sci, Tucson, AZ 85721 USA..
    Burgess, Shane C.
    Univ Arizona, Coll Agr & Life Sci, Tucson, AZ 85721 USA..
    Grabherr, Manfred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Friedman-Einat, Miriam
    Agr Res Org, Volcani Ctr, Rishon Leziyyon, Israel..
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA..
    Correspondence on Lovell et al.: identification of chicken genes previously assumed to be evolutionarily lost2017In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 18, article id 112Article in journal (Refereed)
    Abstract [en]

    Through RNA-Seq analyses, we identified 137 genes that are missing in chicken, including the long-sought-after nephrin and tumor necrosis factor genes. These genes tended to cluster in GC-rich regions that have poor coverage in genome sequence databases. Hence, the occurrence of syntenic groups of vertebrate genes that have not been observed in Aves does not prove the evolutionary loss of such genes.

  • 32. Braunschweig, Martin H
    et al.
    Van Laere, Anne-Sophie
    Buys, Nadine
    Andersson, Leif
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Göran
    IGF2 antisense transcript expression in porcine postnatal muscle is affected by a quantitative trait nucleotide in intron 3.2004In: Genomics, ISSN 0888-7543, Vol. 84, no 6, p. 1021-9Article in journal (Refereed)
  • 33.
    Brunberg, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Cothran, Gus
    Sandberg, Kaj
    Mikko, Sofia
    Lindgren, Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A missense mutation in PMEL17 is associated with the Silver coat color in the horse2006In: BMC Genetics, ISSN 1471-2156, E-ISSN 1471-2156, Vol. 7, p. 46-Article in journal (Refereed)
    Abstract [en]

    Background: The Silver coat color, also called Silver dapple, in the horse is characterized by dilution of the black pigment in the hair. This phenotype shows an autosomal dominant inheritance. The effect of the mutation is most visible in the long hairs of the mane and tail, which are diluted to a mixture of white and gray hairs. Herein we describe the identification of the responsible gene and a missense mutation associated with the Silver phenotype.

    Results: Segregation data on the Silver locus (Z) were obtained within one half-sib family that consisted of a heterozygous Silver colored stallion with 34 offspring and their 29 non-Silver dams. We typed 41 genetic markers well spread over the horse genome, including one single microsatellite marker (TKY284) close to the candidate gene PMEL17 on horse chromosome 6 (ECA6q23). Significant linkage was found between the Silver phenotype and TKY284 (theta = 0, z = 9.0). DNA sequencing of PMEL17 in Silver and non-Silver horses revealed a missense mutation in exon 11 changing the second amino acid in the cytoplasmic region from arginine to cysteine (Arg618Cys). This mutation showed complete association with the Silver phenotype across multiple horse breeds, and was not found among non-Silver horses with one clear exception; a chestnut colored individual that had several Silver offspring when mated to different non-Silver stallions also carried the exon 11 mutation. In total, 64 Silver horses from six breeds and 85 non-Silver horses from 14 breeds were tested for the exon 11 mutation. One additional mutation located in intron 9, only 759 bases from the missense mutation, also showed complete association with the Silver phenotype. However, as one could expect to find several non-causative mutations completely associated with the Silver mutation, we argue that the missense mutation is more likely to be causative.

    Conclusion: The present study shows that PMEL17 causes the Silver coat color in the horse and enable genetic testing for this trait.

  • 34. Bruun, C S
    et al.
    Jörgensen, C B
    Nielsen, V H
    Andersson, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fredholm, M
    Evaluation of the porcine melanocortin 4 receptor (MC4R) gene as a positional candidate for a fatness QTL in a cross between Landrace and Hampshire.2006In: Anim Genet, ISSN 0268-9146, Vol. 37, no 4, p. 359-62Article in journal (Refereed)
  • 35.
    Carlborg, Örjan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Jacobsson, Lina
    Ahgren, Per
    Siegel, Paul
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Epistasis and the release of genetic variation during long-term selection.2006In: Nat Genet, ISSN 1061-4036, Vol. 38, no 4, p. 418-20Article in journal (Refereed)
  • 36.
    Carlborg, Örjan
    et al.
    SLU.
    Kerje, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Schütz, Karin
    Jacobsson, Lina
    Jensen, Per
    Andersson, Leif
    A Global Search Reveals Epistatic Interaction Between QTL for Early Growth in the Chicken2003In: Genome Research, no 13, p. 413-421Article in journal (Refereed)
  • 37.
    Carneiro, Miguel
    et al.
    Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO InBIO, Campus Agr Vairao, P-4485661 Vairao, Portugal.;Univ Porto, Fac Ciencias, Dept Biol, P-4169007 Oporto, Portugal..
    Hu, Dou
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Archer, John
    Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO InBIO, Campus Agr Vairao, P-4485661 Vairao, Portugal..
    Feng, Chungang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Afonso, Sandra
    Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO InBIO, Campus Agr Vairao, P-4485661 Vairao, Portugal..
    Chen, Congying
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Jiangxi Agr Univ, State Key Lab Pig Genet Improvement & Prod Techno, Nanchang 330045, Jiangxi, Peoples R China..
    Blanco-Aguiar, Jose A.
    Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO InBIO, Campus Agr Vairao, P-4485661 Vairao, Portugal.;Inst Invest Recursos Cineget IREC CSIC UCLM JCCM, Ciudad Real 13071, Spain..
    Garreau, Herve
    Univ Toulouse, INRA, Genet Physiol & Syst Elevage UMR1388, F-31326 Castanet Tolosan, France..
    Boucher, Samuel
    FFC, F-75009 Paris, France..
    Ferreira, Paula G.
    Univ Porto, ICBAS, Dept Anat, P-4050343 Oporto, Portugal.;Univ Porto, UMIB, P-4050343 Oporto, Portugal..
    Ferrand, Nuno
    Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, CIBIO InBIO, Campus Agr Vairao, P-4485661 Vairao, Portugal.;Univ Porto, Fac Ciencias, Dept Biol, P-4169007 Oporto, Portugal.;Univ Johannesburg, Fac Sci, Dept Zool, ZA-2006 Auckland Pk, South Africa..
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden.;Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. ETH, Inst Anim Sci, CH-8092 Zurich, Switzerland..
    Dwarfism and Altered Craniofacial Development in Rabbits Is Caused by a 12.1 kb Deletion at the HMGA2 Locus2017In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 205, no 2, p. 955-965Article in journal (Refereed)
    Abstract [en]

    The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds. Here, we show that the dwarf allele constitutes a similar to 12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene. HMGA2 has been frequently associated with variation in body size across species. Homozygotes for null alleles are viable in mice but not in rabbits and probably not in humans. RNA-sequencing analysis of rabbit embryos showed that very few genes (4-29 genes) were differentially expressed among the three HMGA2/dwarf genotypes, suggesting that dwarfism and inviability in rabbits are caused by modest changes in gene expression. Our results show that HMGA2 is critical for normal expression of IGF2BP2, which encodes an RNA-binding protein. Finally, we report a catalog of regions of elevated genetic differentiation between dwarf and normal-size rabbits, including LCORL-NCAPG, STC2, HOXD cluster, and IGF2BP2. Levels and patterns of genetic diversity at the LCORL-NCAPG locus further suggest that small size in dwarf breeds was enhanced by crosses with wild rabbits. Overall, our results imply that small size in dwarf rabbits results from a large effect, loss-of-function (LOF) mutation in HMGA2 combined with polygenic selection.

  • 38. Carneiro, Miguel
    et al.
    Piorno, Vicente
    Rubin, Carl-Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Alves, Joel M.
    Ferrand, Nuno
    Alves, Paulo C.
    Andersson, Leif
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Candidate genes underlying heritable differences in reproductive seasonality between wild and domestic rabbits2015In: Animal Genetics, ISSN 0268-9146, E-ISSN 1365-2052, Vol. 46, no 4, p. 418-425Article in journal (Refereed)
    Abstract [en]

    Reproductive seasonality is a trait that often differs between domestic animals and their wild ancestors, with domestic animals showing prolonged or even continuous breeding seasons. However, the genetic basis underlying this trait is still poorly understood for most species, and because environmental factors and resource availability are known to play an important role in determining breeding seasons, it is also not clear in most cases to what extent this phenotypic shift is determined by the more lenient captive conditions or by genetic factors. Here, using animals resulting from an initial cross between wild and domestic rabbits followed by two consecutive backcrosses (BC1 and BC2) to wild rabbits, we evaluated the yearly distribution of births for the different generations. Similar to domestic rabbits, F1 animals could be bred all year round but BC1 and BC2 animals showed a progressive and significant reduction in the span of the breeding season, providing experimental evidence that reduced seasonal breeding in domestic rabbits has a clear genetic component and is not a simple by-product of rearing conditions. We then took advantage of a recently published genome-wide scan of selection in the domesticated lineage and searched for candidate genes potentially associated with this phenotypic shift. Candidate genes located within regions targeted by selection include well-known examples of genes controlling clock functions (CRY1 and NR3C1) and reproduction (PRLR).

  • 39. Carneiro, Miguel
    et al.
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Di Palma, Federica
    Albert, Frank W.
    Alfoeldi, Jessica
    Barrio, Alvaro Martinez
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Pielberg, Gerli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rafati, Nima
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sayyab, Shumaila
    Turner-Maier, Jason
    Younis, Shady
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Afonso, Sandra
    Aken, Bronwen
    Alves, Joel M.
    Barrell, Daniel
    Bolet, Gerard
    Boucher, Samuel
    Burbano, Hernan A.
    Campos, Rita
    Chang, Jean L.
    Duranthon, Veronique
    Fontanesi, Luca
    Garreau, Herve
    Heiman, David
    Johnson, Jeremy
    Mage, Rose G.
    Peng, Ze
    Queney, Guillaume
    Rogel-Gaillard, Claire
    Ruffier, Magali
    Searle, Steve
    Villafuerte, Rafael
    Xiong, Anqi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Young, Sarah
    Forsberg-Nilsson, Karin
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Good, Jeffrey M.
    Lander, Eric S.
    Ferrand, Nuno
    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.
    Andersson, Leif
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication2014In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 345, no 6200, p. 1074-1079Article in journal (Refereed)
    Abstract [en]

    The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.

  • 40. Cassini, Pamela
    et al.
    Montironi, Alberto
    Botti, Sara
    Hori, Tetsuo
    Okhawa, Haruo
    Stella, Alessandra
    Andersson, Leif
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Giuffra, Elisabetta
    Genetic analysis of anal atresia in pigs: evidence for segregation at two main loci.2005In: Mamm Genome, ISSN 0938-8990, Vol. 16, no 3, p. 164-70Article in journal (Refereed)
  • 41.
    Chen, Junfeng
    et al.
    Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA..
    Huddleston, John
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.;Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA..
    Buckley, Reuben M.
    Univ Adelaide, Sch Biol Sci, Adelaide, SA 5005, Australia..
    Malig, Maika
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA..
    Lawhon, Sara D.
    Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA..
    Skow, Loren C.
    Texas A&M Univ, Coll Vet Med, Dept Vet Integrat Biosci, College Stn, TX 77843 USA..
    Lee, Mi Ok
    Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA..
    Eichler, Evan E.
    Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.;Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA..
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Texas A&M Univ, Coll Vet Med, Dept Vet Integrat Biosci, College Stn, TX 77843 USA.;Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Womack, James E.
    Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA..
    Bovine NK-lysin: Copy number variation and functional diversification2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 52, p. E7223-E7229Article in journal (Refereed)
    Abstract [en]

    NK-lysin is an antimicrobial peptide and effector protein in the host innate immune system. It is coded by a single gene in humans and most other mammalian species. In this study, we provide evidence for the existence of four NK-lysin genes in a repetitive region on cattle chromosome 11. The NK2A, NK2B, and NK2C genes are tandemly arrayed as three copies in similar to 30-35-kb segments, located 41.8 kb upstream of NK1. All four genes are functional, albeit with differential tissue expression. NK1, NK2A, and NK2B exhibited the highest expression in intestine Peyer's patch, whereas NK2C was expressed almost exclusively in lung. The four peptide products were synthesized ex vivo, and their antimicrobial effects against both Gram-positive and Gram-negative bacteria were confirmed with a bacteria-killing assay. Transmission electron microcopy indicated that bovine NK-lysins exhibited their antimicrobial activities by lytic action in the cell membranes. In summary, the single NK-lysin gene in other mammals has expanded to a four-member gene family by tandem duplications in cattle; all four genes are transcribed, and the synthetic peptides corresponding to the core regions are biologically active and likely contribute to innate immunity in ruminants.

  • 42. Curik, Ino
    et al.
    Druml, Thomas
    Seltenhammer, Monika
    Sundström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pielberg, Gerli Rosengren
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Solkner, Johann
    Complex Inheritance of Melanoma and Pigmentation of Coat and Skin in Grey Horses2013In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 2, p. e1003248-Article in journal (Refereed)
    Abstract [en]

    The dominant phenotype of greying with age in horses, caused by a 4.6-kb duplication in intron 6 of STX17, is associated with a high incidence of melanoma and vitiligo-like skin depigmentation. However, the progressive greying and the incidence of melanoma, vitiligo-like depigmentation, and amount of speckling in these horses do not follow a simple inheritance pattern. To understand their inheritance, we analysed the melanoma grade, grey level, vitiligo grade, and speckling grade of 1,119 Grey horses (7,146 measurements) measured in six countries over a 9-year period. We estimated narrow sense heritability (h(2)), and we decomposed this parameter into polygenic heritability (h(POLY)(2)), heritability due to the Grey (STX17) mutation (h(STX17)(2)), and heritability due to agouti (ASIP) locus (h(ASIP)(2)). A high heritability was found for greying (h(2) = 0.79), vitiligo (h(2) = 0.63), and speckling (h(2) = 0.66), while a moderate heritability was estimated for melanoma (h(2) = 0.37). The additive component of ASIP was significantly different from zero only for melanoma (h(ASIP)(2) = 0.02). STX17 controlled large proportions of phenotypic variance (h(STX17)(2) = 0.18-0.55) and overall heritability (h(STX17)(2)/h(2) = 0.28-0.83) for all traits. Genetic correlations among traits were estimated as moderate to high, primarily due to the effects of the STX17 locus. Nevertheless, the correlation between progressive greying and vitiligo-like depigmentation remained large even after taking into account the effects of STX17. We presented a model where four traits with complex inheritance patterns are strongly influenced by a single mutation. This is in line with evidence of recent studies in domestic animals indicating that some complex traits are, in addition to the large number of genes with small additive effects, influenced by genes of moderate-to-large effect. Furthermore, we demonstrated that the STX17 mutation explains to a large extent the moderate to high genetic correlations among traits, providing an example of strong pleiotropic effects caused by a single gene.

  • 43. de Koning, D J
    et al.
    Pong-Wong, R
    Varona, L
    Evans, G J
    Giuffra, E
    Sanchez, A
    Plastow, G
    Noguera, J L
    Andersson, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Haley, C S
    Full pedigree quantitative trait locus analysis in commercial pigs using variance components.2003In: J Anim Sci, ISSN 0021-8812, Vol. 81, no 9, p. 2155-63Article in journal (Refereed)
  • 44.
    Dorshorst, Ben
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Harun-Or-Rashid, Mohammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Bagherpoor, Alireza Jian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Rubin, Carl-Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ashwell, Chris
    Gourichon, David
    Tixier-Boichard, Michèle
    Hallböök, Finn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Andersson, Leif
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A Genomic Duplication is Associated with Ectopic Eomesodermin Expression in the Embryonic Chicken Comb and Two Duplex-comb Phenotypes2015In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 3, article id e1004947Article in journal (Refereed)
    Abstract [en]

    Duplex-comb (D) is one of three major loci affecting comb morphology in the domestic chicken. Here we show that the two Duplex-comb alleles, V-shaped (D*V) and Buttercup (D*C), are both associated with a 20 Kb tandem duplication containing several conserved putative regulatory elements located 200 Kb upstream of the eomesodermin gene (EOMES). EOMES is a T-box transcription factor that is involved in mesoderm specification during gastrulation. In D*V and D*C chicken embryos we find that EOMES is ectopically expressed in the ectoderm of the comb-developing region as compared to wild-type embryos. The confinement of the ectopic expression of EOMES to the ectoderm is in stark contrast to the causal mechanisms underlying the two other major comb loci in the chicken (Rose-comb and Pea-comb) in which the transcription factors MNR2 and SOX5 are ectopically expressed strictly in the mesenchyme. Interestingly, the causal mutations of all three major comb loci in the chicken are now known to be composed of large-scale structural genomic variants that each result in ectopic expression of transcription factors. The Duplex-comb locus also illustrates the evolution of alleles in domestic animals, which means that alleles evolve by the accumulation of two or more consecutive mutations affecting the phenotype. We do not yet know whether the V-shaped or Buttercup allele correspond to the second mutation that occurred on the haplotype of the original duplication event.

  • 45.
    Dorshorst, Ben
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Henegar, Corneliu
    Liao, Xiaoping
    Almén, Markus Sällman
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ito, Shosuke
    Wakamatsu, Kazumasa
    Stothard, Paul
    Van Doormaal, Brian
    Plastow, Graham
    Barsh, Gregory S.
    Andersson, Leif
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha (COPA) Gene2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0128969Article in journal (Refereed)
    Abstract [en]

    Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 1 receptor (MC1R) gene, a central determinant of black (eumelanin) vs. red/brown pheomelanin synthesis across animal species. The major MC1R alleles in Holsteins are Dominant Black (MC1R(D)) and Recessive Red (MC1R(e)). A novel form of dominant red coat color was first observed in an animal born in 1980. The mutation underlying this phenotype was named Dominant Red and is epistatic to the constitutively activated MC1R(D). Here we show that a missense mutation in the coatomer protein complex, subunit alpha (COPA), a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle. The mutation results in an arginine to cysteine substitution at an amino acid residue completely conserved across eukaryotes. Despite this high level of conservation we show that both heterozygotes and homozygotes are healthy and viable. Analysis of hair pigment composition shows that the Dominant Red phenotype is similar to the MC1R Recessive Red phenotype, although less effective at reducing eumelanin synthesis. RNA-seq data similarly show that Dominant Red animals achieve predominantly pheomelanin synthesis by down regulating genes normally required for eumelanin synthesis. COPA is a component of the coat protein I seven subunit complex that is involved with retrograde and cis-Golgi intracellular coated vesicle transport of both protein and RNA cargo. This suggests that Dominant Red may be caused by aberrant MC1R protein or mRNA trafficking within the highly compartmentalized melanocyte, mimicking the effect of the Recessive Red loss of function MC1R allele.

  • 46.
    Dorshorst, Ben
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Molin, Anna-Maja
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johansson, Anna M.
    Stromstedt, Lina
    Pham, Manh-Hung
    Chen, Chih-Feng
    Hallböök, Finn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Ashwell, Chris
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A Complex Genomic Rearrangement Involving the Endothelin 3 Locus Causes Dermal Hyperpigmentation in the Chicken2011In: PLoS Genetics, ISSN 1553-7390, Vol. 7, no 12, p. e1002412-Article in journal (Refereed)
    Abstract [en]

    Dermal hyperpigmentation or Fibromelanosis (FM) is one of the few examples of skin pigmentation phenotypes in the chicken, where most other pigmentation variants influence feather color and patterning. The Silkie chicken is the most widespread and well-studied breed displaying this phenotype. The presence of the dominant FM allele results in extensive pigmentation of the dermal layer of skin and the majority of internal connective tissue. Here we identify the causal mutation of FM as an inverted duplication and junction of two genomic regions separated by more than 400 kb in wild-type individuals. One of these duplicated regions contains endothelin 3 (EDN3), a gene with a known role in promoting melanoblast proliferation. We show that EDN3 expression is increased in the developing Silkie embryo during the time in which melanoblasts are migrating, and elevated levels of expression are maintained in the adult skin tissue. We have examined four different chicken breeds from both Asia and Europe displaying dermal hyperpigmentation and conclude that the same structural variant underlies this phenotype in all chicken breeds. This complex genomic rearrangement causing a specific monogenic trait in the chicken illustrates how novel mutations with major phenotypic effects have been reused during breed formation in domestic animals.

  • 47. Drögemüller, Cord
    et al.
    Giese, Alexander
    Martins-Wess, Flávia
    Wiedemann, Sabine
    Andersson, Leif
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Brenig, Bertram
    Fries, Ruedi
    Leeb, Tosso
    The mutation causing the black-and-tan pigmentation phenotype of Mangalitza pigs maps to the porcine ASIP locus but does not affect its coding sequence.2006In: Mamm Genome, ISSN 0938-8990, Vol. 17, no 1, p. 58-66Article in journal (Refereed)
  • 48. Ek, Weronica
    et al.
    Sahlqvist, Anna-Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Crooks, Lucy
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Sgonc, Roswitha
    Dietrich, Hermann
    Wick, Georg
    Ekwall, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Carlborg, Örjan
    Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Kerje, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens2012In: Developmental and Comparative Immunology, ISSN 0145-305X, E-ISSN 1879-0089, Vol. 38, no 2, p. 352-359Article in journal (Refereed)
    Abstract [en]

    Systemic sclerosis (SSc) or scleroderma is a rare, autoimmune, multi-factorial disease characterized by early microvascular alterations, inflammation, and fibrosis. Chickens from the UCD-200 line develop a hereditary SSc-like disease, showing all the hallmarks of the human disorder, which makes this line a promising model to study genetic factors underlying the disease. A backcross was generated between UCD-200 chickens and its wild ancestor - the red jungle fowl and a genome-scan was performed to identify loci affecting early (21days of age) and late (175days of age) ischemic lesions of the comb. A significant difference in frequency of disease was observed between sexes in the BC population, where the homogametic males were more affected than females, and there was evidence for a protective W chromosome effect. Three suggestive disease predisposing loci were mapped to chromosomes 2, 12 and 14. Three orthologues of genes implicated in human SSc are located in the QTL region on chromosome 2, TGFRB1, EXOC2-IRF4 and COL1A2, as well as CCR8, which is more generally related to immune function. IGFBP3 is also located within the QTL on chromosome 2 and earlier studies have showed increased IGFBP3 serum levels in SSc patients. To our knowledge, this study is the first to reveal a potential genetic association between IGFBP3 and SSc. Another gene with an immunological function, SOCS1, is located in the QTL region on chromosome 14. These results illustrate the usefulness of the UCD-200 chicken as a model of human SSc and motivate further in-depth functional studies of the implicated candidate genes.

  • 49. Ek, Weronica
    et al.
    Strömstedt, Lina
    Wahlberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Siegel, Paul
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Carlborg, Örjan
    SLU.
    Genetic analysis of metabolic traits in an intercross between body weight-selected chicken lines2010In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 42, no 1, p. 20-22Article in journal (Refereed)
    Abstract [en]

    A network of four interacting loci has been reported previously to influence growth in two lines of chickens divergently selected for body weight at 56 days of age. Located on chromosomes 3 (Growth4), 4 (Growth6), 7 (Growth9), and 20 (Growth12), they explained nearly half of the difference in body weight at selection age between the two lines. The original study reported effects on body weight and fat deposition, but no attempts were made to explore the effects of the network on other phenotypes measured in the F(2) population. In this study we conducted further analyses to evaluate the specific effects of the four-locus network on other metabolic traits as well as refining results from the original study by including a larger number of genetic markers in the quantitative trait locus (QTL) regions. We confirm the previously described effect of the epistatic network on body weight and show that the network increases the total amount of muscle and fat as well as the weight of the internal organs. The network as a whole did not change the relative content of any studied organs or tissues in the body. There was, however, a significant interaction between the loci on chromosomes 3 and 7 that changed the relative proportion of abdominal fat and breast muscle in the chicken by increasing abdominal fat weight without a corresponding increase in muscle mass.

  • 50.
    Eriksson, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hellström, Anders
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Wang, Chao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sayyab, Shumaila
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences.
    Kerje, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    David, Gourichon
    INRA, PEAT, Nouzilly, France.
    Bed'hom, Bertrand
    INRA, AgroParisTech, Animal Genetics and Integrative Biology.
    Tixier-Boichard, Michèle
    INRA, AgroParisTech, Animal Genetics and Integrative Biology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    A frameshift mutation in COMTD1 specifically dilutes pheomelanin pigmentation in chickenManuscript (preprint) (Other academic)
1234 1 - 50 of 193
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf