Inter- and intra-breed genome-wide copy number diversity in a large cohort of European equine breeds

Abstract

BackgroundCopy Number Variation (CNV) is a common form of genetic variation underlying animal evolution and phenotypic diversity across a wide range of species. In the mammalian genome, high frequency of CNV differentiation between breeds may be candidates for population-specific selection. However, CNV differentiation, selection and its population genetics have been poorly explored in horses.ResultsWe investigated the patterns, population variation and gene annotation of CNV using the Axiom® Equine Genotyping Array (670,796 SNPs) from a large cohort of individuals (N = 1755) belonging to eight European horse breeds, varying from draught horses to several warmblood populations. After quality control, 152,640 SNP CNVs (individual markers), 18,800 segment CNVs (consecutive SNP CNVs of same gain/loss state or both) and 939 CNV regions (CNVRs; overlapping segment CNVs by at least 1 bp) compared to the average signal of the reference (Belgian draught horse) were identified. Our analyses showed that Equus caballus chromosome 12 (ECA12) was the most enriched in segment CNV gains and losses (~ 3% average proportion of the genome covered), but the highest number of segment CNVs were detected on ECA1 and ECA20 (regardless of size). The Friesian horses showed private SNP CNV gains (> 20% of the samples) on ECA1 and Exmoor ponies displayed private SNP CNV losses on ECA25 (> 20% of the samples). The Warmblood cluster showed private SNP CNV gains located in ECA9 and Draught cluster showed private SNP CNV losses located in ECA7. The length of the CNVRs ranged from 1 kb to 21.3 Mb. A total of 10,612 genes were annotated within the CNVRs. The PANTHER annotation of these genes showed significantly under- and overrepresented gene ontology biological terms related to cellular processes and immunity (Bonferroni P-value < 0.05). We identified 80 CNVRs overlapping with known QTL for fertility, coat colour, conformation and temperament. We also report 67 novel CNVRs.ConclusionsThis work revealed that CNV patterns, in the genome of some European horse breeds, occurred in specific genomic regions. The results provide support to the hypothesis that high frequency private CNVs residing in genes may potentially be responsible for the diverse phenotypes seen between horse breeds.

Whole genome detection of sequence and structural polymorphism in six diverse horses

“…Of the identified CNVs, the number of gains was comparable to the number of losses for all horses ( Table 2, 721 mean gains vs 819 mean losses). 1887 of the CNVs detected in this study overlapped fully with CNVs reported earlier in a recent study [26] (S7 Table). Since many of the gains and losses are shared between horses, we hypothesize that those are artifacts of the computational assembly of Equ-Cab3.0, compressing regions of repetitive sequences and highly homologous gene families.…”

Characterization of a Homozygous Deletion of Steroid Hormone Biosynthesis Genes in Horse Chromosome 29 as a Risk Factor for Disorders of Sex Development and Reproduction

“…The deleted region in ECA29 is embedded in a larger common CNVR that has been found in the general equine population of diverse origins by several previous studies [22,25,41,42]. The most extensive recent genome-wide analysis of 939 CNVRs in 1755 horses of 8 European breeds, detected the larger 714 kb common deletion-duplication CNVR (CNVR915) in 1204 (68.6%) horses [25]. As a notable contrast, the homozygous deletion of the smaller 200 kb region is rare and was found only in about 4.7% of phenotypically normal horses used in this study, and in 0% to 7.6% of general equine population from other studies (Tables 3 and 4).…”

“…In order to estimate the frequency of the homozygous deletion in the general equine population, we analyzed publicly available WGS and 670K SNP array data for the region chr29: 29,741,143-29,952,177 (Table 4). The frequency of homozygous deletion carriers varies considerably between the studies being 0-1% among global warmblood and pony breeds [26,27], but reaching over 7% in a recent study, which is strongly biased towards draught horses [25]. Collectively, the frequency of homozygous deletion in general equine population is lower (5.6%) than that among horses with DSDs and fertility problems (8.1%).…”

“…Based on published data, the frequency of the homozygous deletion is extremely low (0% to 1%) among 26 global warmblood and pony breeds [26,27]. For example, the larger CNVR is present in 84% (216/256) of Exmoor ponies studied for CNVs [25], but none of these carry the homozygous deletion of the smaller region [26] (Table 4). At the same time, the frequency of D/D individuals seems to be considerably higher (7.6%) among European draught breeds [25] and it would be of future interest to compare the genotyping data with reproductive phenotypes in these breeds.…”

“…In addition, whole genome sequence (WGS) and/or high density 670K SNP genotyping data from publications [25][26][27] were used for population analysis. Horses from these cohorts were not specifically phenotyped for sex development or fertility.…”