Identification of candidate genes associated with growth and development of sheep from a crossbred population using genome-wide association studies

T. Deniskova, O. Koshkina, S. Petrov, A. Sermyagin, N. Zinovieva
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Abstract

The article presents the results of a search for genome-wide associations with phenotypic traits characterizing the growth and development of sheep from a crossbred population obtained from crossing Romanov sheep and F1 hybrid rams (Romanov sheep x Katahdin). The phenotype database included ten body measurements (withers height, sacral height, back height, chest depth, chest width, ischial tuberosity width, body length, oblique body length, chest girth, pastern girth) recorded at the age of 6 days, 3, 6 and 9 months. Genotyping of sheep was carried out using high-density DNA chips containing about 600,000 SNP markers. Genome-wide association studies (GWAS) were performed using regression analysis in the STATISTICA 10 program. The search for candidate genes localized in the SNP region was performed using Ensembl genome browser 110. There was carried out an analysis of the matches of the identified SNPs with known quantitative trait loci (QTLs) described in the Sheep Quantitative Trait Locus Database. There were found SNPs that were significantly associated with the studied phenotypic traits overlapped with the QTLs, among which the most common categories were “Body weight (slaughter)”, “Muscle weight in carcass”, “Body weight (live)” and “Bone weight in carcass”. There has been established that SNPs significantly associated with exterior traits were localized within or in the immediate vicinity of 64 genes. There were found potential candidates regulating the growth of muscle (FOXO3, PRKAG3, MYOZ2, and ANKRD1) and cartilage tissues FGF12) and involved in metabolic processes, which were critical for the growth of lambs (CLDN, ALB, and MRC1). Along with the known in sheep functional candidates (CAST and SCD5) , there were identified genes that were not previously described in sheep, but regulated growth and development processes in other livestock species including genes RAB28, PRKAG3 and  FOXO3. The identified SNPs can be recommended for inclusion in marker-guided selection programs in sheep breeding.
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利用全基因组关联研究确定与杂交绵羊生长发育相关的候选基因
文章介绍了对罗曼诺夫绵羊和 F1 杂交公羊(罗曼诺夫绵羊 x 卡塔丁绵羊)杂交种群中绵羊生长发育表型特征的全基因组关联的研究结果。表型数据库包括 6 日龄、3 个月、6 个月和 9 个月时记录的 10 项身体测量数据(肩高、骶高、背高、胸深、胸宽、跗关节宽、体长、斜体长、胸围、趾间距)。绵羊的基因分型是通过含有约 600,000 个 SNP 标记的高密度 DNA 芯片进行的。利用 STATISTICA 10 程序中的回归分析进行了全基因组关联研究(GWAS)。使用 Ensembl 基因组浏览器 110 搜索 SNP 区域的候选基因。对鉴定出的 SNP 与绵羊数量性状基因位点数据库(Sheep Quantitative Trait Locus Database)中描述的已知数量性状基因位点(QTLs)的匹配情况进行了分析。结果发现,与所研究表型性状显著相关的 SNP 与 QTL 重叠,其中最常见的类别是 "体重(屠宰)"、"胴体肌肉重量"、"体重(活体)"和 "胴体骨骼重量"。研究发现,与外部性状显著相关的 SNPs 定位于 64 个基因内部或附近。发现了调节肌肉(FOXO3、PRKAG3、MYOZ2 和 ANKRD1)和软骨组织(FGF12)生长以及参与代谢过程的潜在候选基因,这些基因对羔羊的生长至关重要(CLDN、ALB 和 MRC1)。除了已知的绵羊功能候选基因(CAST 和 SCD5)外,还发现了以前未在绵羊中描述过、但在其他家畜物种中调控生长和发育过程的基因,包括 RAB28、PRKAG3 和 FOXO3。这些已鉴定的 SNPs 可推荐用于绵羊育种中的标记引导选择计划。
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