Genome-Wide Detection of Copy Number Variations and Their Association With Distinct Phenotypes in the World’s Sheep

Abstract

Copy number variations (CNVs) are a major source of structural variation in mammalian genomes. Here, we characterized the genome-wide CNV in 2059 sheep from 67 populations all over the world using the Ovine Infinium HD (600K) SNP BeadChip. We tested their associations with distinct phenotypic traits by conducting multiple independent genome-wide tests. In total, we detected 7547 unique CNVs and 18,152 CNV events in 1217 non-redundant CNV regions (CNVRs), covering 245 Mb (∼10%) of the whole sheep genome. We identified seven CNVRs with frequencies correlating to geographical origins and 107 CNVRs overlapping 53 known quantitative trait loci (QTLs). Gene ontology and pathway enrichment analyses of CNV-overlapping genes revealed their common involvement in energy metabolism, endocrine regulation, nervous system development, cell proliferation, immune, and reproduction. For the phenotypic traits, we detected significantly associated (adjusted P < 0.05) CNVRs harboring functional candidate genes, such as SBNO2 for polycerate; PPP1R11 and GABBR1 for tail weight; AKT1 for supernumerary nipple; CSRP1, WNT7B, HMX1, and FGFR3 for ear size; and NOS3 and FILIP1 in Wadi sheep; SNRPD3, KHDRBS2, and SDCCAG3 in Hu sheep; NOS3, BMP1, and SLC19A1 in Icelandic; CDK2 in Finnsheep; MICA in Romanov; and REEP4 in Texel sheep for litter size. These CNVs and associated genes are important markers for molecular breeding of sheep and other livestock species.

Identification of Copy Number Variations and Genetic Diversity in Italian Insular Sheep Breeds

“…The proteins of the LRP1B gene (within CNVR_59, common to all breeds), participate in a wide range of physiological processes, including the regulation of lipid metabolism, neurodevelopment, and transport of nutrients and vitamins [ 52 , 53 ], but also in cell proliferation process, making it a potential candidate gene for the supernumerary nipple phenotype [ 54 ]. The KHDRBS2 gene, within the CNVR_310 with the highest variance, has been associated with fertility and reproductive traits in cattle [ 55 ], goat [ 56 ], and sheep [ 57 ]. Moreover, the FILIP1 gene (CNVR_185), reported by Salehian-Dehkordi et al [ 57 ] has been linked with fertility traits.…”

“…The KHDRBS2 gene, within the CNVR_310 with the highest variance, has been associated with fertility and reproductive traits in cattle [ 55 ], goat [ 56 ], and sheep [ 57 ]. Moreover, the FILIP1 gene (CNVR_185), reported by Salehian-Dehkordi et al [ 57 ] has been linked with fertility traits. The ACAD9 gene is a recently identified acyl-CoA dehydrogenase that demonstrates maximum activity with unsaturated long-chain acyl-CoAs [ 58 ].…”

Genome-wide identification of copy number variation and association with fat deposition in thin and fat-tailed sheep breeds

“…Fat tail in sheep is an adaptive response to harsh environmental conditions and is a source of energy in adverse environmental conditions such as periods of food shortage and severe cold 48 . Salehian-Dehkordi et al identified various CNV-related genes associated with climatic adaptation and artificial selection in sheep 29 .…”

“…Salehian-Dehkordi et al using the genome-wide SNPs detected eight CNVRs associated with fat deposition in the tails in the Large-tailed and Small-tailed Han sheep horboting PPP1R11 and GABBR1 genes to be involved in fat deposition in the tails 29 . Zhu et al using high-density SNP arrays detected genome-wide CNVs in Chinese indigenous sheep with different types of tails and reported CNVRs including genes associated with fat deposition 30 .…”

Genome-wide analysis of CNVs in three populations of Tibetan sheep using whole-genome resequencing

“…Unlike SNPs, which refer to the substitution, deletion or insertion of just a single nucleotide for another, CNVs involve fragmental variation even larger than 1000 bp in size ( Iafrate et al, 2004 ; Feuk et al, 2006 ). Therefore, it has been widely recognized that CNVs have the potential to markedly affect phenotypic traits of domestic animals ( Salehian-Dehkordi et al, 2021 ).…”