title: Genetic effects of FASN, PPARGC1A, ABCG2 and IGF1 revealing the association with milk fatty acids in a Chinese Holstein cattle population based on a post genome-wide association study.
abstract: A previous genome-wide association study deduced that one (ARS-BFGL-NGS-39328), two (Hapmap26001-BTC-038813 and Hapmap31284-BTC-039204), two (Hapmap26001-BTC-038813 and BTB-00246150), and one (Hapmap50366-BTA-46960) genome-wide significant single nucleotide polymorphisms (SNPs) associated with milk fatty acids were close to or within the fatty acid synthase (FASN), peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A), ATP-binding cassette, sub-family G, member 2 (ABCG2) and insulin-like growth factor 1 (IGF1) genes. To further confirm the linkage and reveal the genetic effects of these four candidate genes on milk fatty acid composition, genetic polymorphisms were identified and genotype-phenotype associations were performed in a Chinese Holstein cattle population.
  
  
  
  Nine SNPs were identified in FASN, among which SNP rs41919985 was predicted to result in an amino acid substitution from threonine (ACC) to alanine (GCC), five SNPs (rs136947640, rs134340637, rs41919992, rs41919984 and rs41919986) were synonymous mutations, and the remaining three (rs41919999, rs132865003 and rs133498277) were found in FASN introns. Only one SNP each was identified for PPARGC1A, ABCG2 and IGF1. Association studies revealed that FASN, PPARGC1A, ABCG2 and IGF1 were mainly associated with medium-chain saturated fatty acids and long-chain unsaturated fatty acids, especially FASN for C10:0, C12:0 and C14:0. Strong linkage disequilibrium was observed among ARS-BFGL-NGS-39328 and rs132865003 and rs134340637 in FASN (D´ > 0.9), and among Hapmap26001-BTC-038813 and Hapmap31284-BTC-039204 and rs109579682 in PPARGC1A (D´ > 0.9). Subsequently, haplotype-based analysis revealed significant associations of the haplotypes encompassing eight FASN SNPs (rs41919999, rs132865003, rs134340637, rs41919992, rs133498277, rs41919984, rs41919985 and rs41919986) with C10:0, C12:0, C14:0, C18:1n9c, saturated fatty acids (SFA) and unsaturated fatty acids (UFA) (P = 0.0204 to P < 0.0001).
  
  
  
  Our study confirmed the linkage between the significant SNPs in our previous genome-wide association study and variants in FASN and PPARGC1A. SNPs within FASN, PPARGC1A, ABCG2 and IGF1 showed significant genetic effects on milk fatty acid composition in dairy cattle, indicating their potential functions in milk fatty acids synthesis and metabolism. The findings presented here provide evidence for the selection of dairy cows with healthier milk fatty acid composition by marker-assisted breeding or genomic selection schemes, as well as furthering our understanding of technological processing aspects of cows' milk.
authors.affiliation: Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China. sundx@cau.edu.cn.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China. zhangslcau@cau.edu.cn.
authors.forename: Shengli
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China.
authors.forename: M A
authors.initials: MA
authors.lastname: Alim
authors.affiliation: Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, China Agricultural University, 2 Yuanmingyuan West Road, Beijing, 100193, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Beijing Dairy Cattle Center, Beijing, 100085, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Beijing Dairy Cattle Center, Beijing, 100085, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000818:Animals; D002417:Cattle; D054890:Fatty Acid Synthase, Type I / Q000235:genetics*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D015810:Linkage Disequilibrium; D008892:Milk / Q000737:chemistry* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D005227:Fatty Acids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D007334:Insulin-Like Growth Factor I; D054890:Fatty Acid Synthase, Type I
keywords: Association analysis; Candidate gene; Haplotype; Milk fatty acids; Single nucleotide polymorphism