A post-GWAS confirming the genetic effects and functional polymorphisms of AGPAT3 gene on milk fatty acids in dairy cattle  

作　　者：Lijun Shi Xin Wu Yuze Yang Zhu Ma Xiaoqing Lv Lin Liu Yanhua Li Feng Zhao Bo Han Dongxiao Sun 

机构地区：[1]Department of Animal Genetics,Breeding and Reproduction,College of Animal Science and Technology,Key Laboratory of Animal Genetics,Breeding and Reproduction of Ministry of Agriculture and Rural Affairs,National Engineering Laboratory for Animal Breeding,China Agricultural University,No.2 Yuanmingyuan West Road,Haidian District,Beijing 100193,China [2]Institute of Animal Science,Chinese Academy of Agricultural Sciences,Beijing 100193,China [3]Beijing General Station of Animal Husbandry,Beijing 100101,China [4]Beijing Dairy Cattle Center,Beijing 100192,China.

出　　处：《Journal of Animal Science and Biotechnology》2021年第1期122-140,共19页畜牧与生物技术杂志（英文版）

基　　金：financially supported by the National Natural Science Foundation of China (31872330, 31802041);Beijing Science and Technology Program (20200105, D171100002417001);earmarked fund for Modern Agroindustry Technology Research System (CARS-36);the Program for Changjiang Scholar and Innovation Research Team in University (IRT_15R62)。

摘　　要：Background: People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids(FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study(GWAS) on milk FAs in dairy cattle, 83 genomewide significant single nucleotide polymorphisms(SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18 index(P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3(AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.Results: Through re-sequencing the complete coding region, and 3000 bp of 5′ and 3′ regulatory regions of the AGPA T3 gene, a total of 17 SNPs were identified, including four in 5′ regulatory region, one in 5′ untranslated region(UTR),three in introns, one in 3′ UTR, and eight in 3′ regulatory region. By the linkage disequilibrium(LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs,respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0(P < 0.0001–0.0384). Further, with Genomatix, we predicted that four SNPs in 5′ regulatory region(g.146702957 G > A, g.146704373 A > G, g.146704618 A > G and g.146704699 G > A) changed the transcription factor binding sites(TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase

关 键 词：AGPAT3 Chinese Holstein Genetic effects Milk fatty acids Potential causal mutation 

分 类 号：S823.2[农业科学—畜牧学]