A genome-wide scan for candidate lethal variants in Thoroughbred horses

Evelyn T. Todd,Sofia Mikko,Natasha A. Hamilton,Rachel A. Ang,Brandon D. Velie,Eric Strand,Åsa Viklund,Susanne Eriksson,Gabriella Lindgren,Peter C. Thomson

doi:10.1038/s41598-020-68946-8

Abstract

Domestic animal populations are often characterised by high rates of inbreeding and low effective population sizes due to selective breeding practices. These practices can result in otherwise rare recessive deleterious alleles drifting to high frequencies, resulting in reduced fertility rates. This study aimed to identify potential recessive lethal haplotypes in the Thoroughbred horse breed, a closed population that has been selectively bred for racing performance. In this study, we identified a haplotype in the LY49B gene that shows strong evidence of being homozygous lethal, despite having high frequencies of heterozygotes in Thoroughbreds and other domestic horse breeds. Variant analysis of whole-genome sequence data identified two SNPs in the 3′UTR of the LY49B gene that may result in loss of function. Analysis of transcriptomic data from equine embryonic tissue revealed that LY49B is expressed in the trophoblast during placentation stage of development. These findings suggest that LY49B may have an essential, but as yet unknown function in the implantation stage of equine development. Further investigation of this region may allow for the development of a genetic test to improve fertility rates in horse populations. Identification of other lethal variants could assist in improving natural levels of fertility in horse populations.

Highlights

Domestic animal populations are often characterised by high rates of inbreeding and low effective population sizes due to selective breeding practices
The SNPs identified in this preliminary analysis mapped to an intronic region in the LY49B gene on ECA6 (Table 1)
The LY49B gene belongs to the LY49 (Killer cell lectin-like receptor subfamily A) family of receptors, which consists of five functional members in Equus caballus[43]

Summary

Introduction

Domestic animal populations are often characterised by high rates of inbreeding and low effective population sizes due to selective breeding practices. Genetic diversity in the Thoroughbred breed has been reduced in recent decades due to the increased commercialisation of popular stallions providing large genetic contributions to the p opulation[40] Such practices are in line with selective breeding p rinciples[41], they could inadvertently increase the frequency of embryonic lethal variants in the population. Reproductive technologies such as artificial insemination are banned in the Thoroughbred population, making the maintenance of high levels of natural fertility imperative. We aimed to determine the frequency of any potentially lethal variants identified in the Thoroughbred population in other horse breeds and examine their transcriptomic profile in embryonic tissue

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Conclusion