title: Genome-wide association mapping for milk fat composition and fine mapping of a QTL for de novo synthesis of milk fatty acids on bovine chromosome 13.
abstract: Bovine milk is widely regarded as a nutritious food source for humans, although the effects of individual fatty acids on human health is a subject of debate. Based on the assumption that genomic selection offers potential to improve milk fat composition, there is strong interest to understand more about the genetic factors that influence the biosynthesis of bovine milk and the molecular mechanisms that regulate milk fat synthesis and secretion. For this reason, the work reported here aimed at identifying genetic variants that affect milk fatty acid composition in Norwegian Red cattle. Milk fatty acid composition was predicted from the nation-wide recording scheme using Fourier transform infrared spectroscopy data and applied to estimate heritabilities for 36 individual and combined fatty acid traits. The recordings were used to generate daughter yield deviations that were first applied in a genome-wide association (GWAS) study with 17,343 markers to identify quantitative trait loci (QTL) affecting fatty acid composition, and next on high-density and sequence-level datasets to fine-map the most significant QTL on BTA13 (BTA for Bos taurus chromosome).
  
  
  
  The initial GWAS revealed 200 significant associations, with the strongest signals on BTA1, 13 and 15. The BTA13 QTL highlighted a strong functional candidate gene for de novo synthesis of short- and medium-chained saturated fatty acids; acyl-CoA synthetase short-chain family member 2. However, subsequent fine-mapping using single nucleotide polymorphisms (SNPs) from a high-density chip and variants detected by resequencing showed that the effect was more likely caused by a second nearby gene; nuclear receptor coactivator 6 (NCOA6). These findings were confirmed with results from haplotype studies. NCOA6 is a nuclear receptor that interacts with transcription factors such as PPARγ, which is a major regulator of bovine milk fat synthesis.
  
  
  
  An initial GWAS revealed a highly significant QTL for de novo-synthesized fatty acids on BTA13 and was followed by fine-mapping of the QTL within NCOA6. The most significant SNPs were either synonymous or situated in introns; more research is needed to uncover the underlying causal DNA variation(s).
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway. hanne-gro.olsen@nmbu.no.
authors.forename: Hanne Gro
authors.initials: HG
authors.lastname: Olsen
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway.
authors.forename: Tim Martin
authors.initials: TM
authors.lastname: Knutsen
authors.affiliation: Department of Mathematical Sciences and Technology, Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway.|Centre for Biospectroscopy and Data Modeling, Nofima AS, Osloveien 1, 1430, Ås, Norway.
authors.forename: Achim
authors.initials: A
authors.lastname: Kohler
authors.affiliation: Geno Breeding and AI Association, 1432, Ås, Norway.
authors.forename: Morten
authors.initials: M
authors.lastname: Svendsen
authors.affiliation: CAMO Software AS, Nedre Vollgate 8, 0158, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gidskehaug
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Grove
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway.
authors.forename: Torfinn
authors.initials: T
authors.lastname: Nome
authors.affiliation: Institute of Marine Research, Flødevigen, 4817, His, Norway.|Department of Natural Sciences, Faculty of Engineering and Science, University of Agder, PO Box 422, 4604, Kristiansand, Norway.
authors.forename: Marte
authors.initials: M
authors.lastname: Sodeland
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway.
authors.forename: Kristil Kindem
authors.initials: KK
authors.lastname: Sundsaasen
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway.
authors.forename: Matthew Peter
authors.initials: MP
authors.lastname: Kent
authors.affiliation: Department of Engineering Cybernetics, Norwegian University of Science and Technology, 7034, Trondheim, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Martens
authors.affiliation: Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, PO Box 5003, 1432, Ås, Norway.
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Lien
mesh_terms: D000818:Animals; D002417:Cattle / Q000235:genetics*; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D005227:Fatty Acids / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D008892:Milk / Q000737:chemistry / Q000378:metabolism*; D040641:Quantitative Trait Loci
chemical_list: D005227:Fatty Acids