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 <i>P</i> < 0.05) CNVRs harboring functional candidate genes, such as <i>SBNO2</i> for polycerate; <i>PPP1R11</i> and <i>GABBR1</i> for tail weight; <i>AKT1</i> for supernumerary nipple; <i>CSRP1</i>, <i>WNT7B</i>, <i>HMX1</i>, and <i>FGFR3</i> for ear size; and <i>NOS3</i> and <i>FILIP1</i> in Wadi sheep; <i>SNRPD3</i>, <i>KHDRBS2</i>, and <i>SDCCAG3</i> in Hu sheep; <i>NOS3</i>, <i>BMP1</i>, and <i>SLC19A1</i> in Icelandic; <i>CDK2</i> in Finnsheep; <i>MICA</i> in Romanov; and <i>REEP4</i> in Texel sheep for litter size. These CNVs and associated genes are important markers for molecular breeding of sheep and other livestock species.