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

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.

Variations in the fecal microbiota and their functions of Thoroughbred, Mongolian, and Hybrid horses

“…that produce SCFAs to supply the host with more energy sources was also higher in Thoroughbred horses than in Jeju horses (15). When comparing the differences in gut microbiota among six horse breeds in a study by Massacci et al,27 genera were found significantly different among breeds (16). Approximately 33% of these 27 bacterial genera were reported to be heritable in humans or other animals (17,18).…”

“…In comparison with Mongolian horses who have substantial stamina (the speed race distance is generally 30–50 km), the suitable race distance of Thoroughbred horses is 1–4 km ( 25 ). In addition, due to severe inbreeding, the fecundity of Thoroughbred horses is relatively poor and not resistant to roughage ( 26 , 27 ). The first filial generation of Mongolian horses (maternal) and Thoroughbred horses (paternal) emerged in the Horqin grassland (Inner Mongolia, China).…”

Impaired Reproductive Function in Equines: From Genetics to Genomics

“…Those mutations were associated with cerebellar abiotrophy (ECA2), hydrocephalus (ECA1), and congenital liver fibrosis (ECA20), among other disorders. Similarly, Todd, et al [57] identified a lethal embryonic haplotype in the LY49B gene on ECA6 which also showed high frequencies of heterozygotes in thoroughbreds, Norwegian-Swedish Coldblooded Trotters and Swedish Warmbloods (Table 3). Both studies indicate, from a genomic point of view, the importance of the partial dominance hypothesis [81], in which an increase in the expression of deleterious recessive alleles due to increased inbreeding could trigger a reduction in fertility by increasing embryonic lethality.…”

Development and validation of a horse reference panel for genotype imputation

“…They detected a couple of variants that potentially influenced stallion fertility, including a splice-site disruption variant in the NOTCH1 gene [ 37 ]. Furthermore, a haplotype in the LY49B gene was detected from genotype data on Thoroughbreds that showed a deficiency of homozygotes, and it represents a strong candidate for containing a recessive lethal mutation [ 38 ].…”

“…The detection of lethal variants can also aid in diminishing the prevalence of genetic disorders and in the optimisation of fertility rates in horses [ 38 , 39 ]. Therefore, we applied an approach based on missing homozygosity to identify putative lethal mutations.…”