Identification of Variants Causing Early Embryonic Loss in Beef Cattle

Reproductive efficiency is among the most important of the productive traits of cattle and yet has a relatively low heritability likely because it is a complex trait with many physiological processes required to correctly function in order to deliver a normal healthy calf. Among the earliest expressed of the fertility component traits is embryonic loss for which a genetic basis has now been established in cattle with the discovery of chromosomal segments containing haplotypes that never occur in homozygous form. Invariably these haplotypes are found to harbor mutations that disrupt genes that are essential for life. Since about 33% of mammalian genes are essential for life, there is considerable opportunity for deleterious mutations in these genes to be driven to moderate frequency in highly selected populations employing artificial insemination. To identify mutations likely to impact fertility via early embryonic loss, we analyzed the genome sequences of 262 taurines and multiple tissue transcriptomes from 153 taurines to identify variants. Among the identified variants, we focused on those that occurred within the open reading frames of genes and designed a new genotyping assay called the GGP-F250 that queried genotype at 227,233 genomic locations. A total of 18,271 animals from 22 breeds were genotyped with the assay and a cluster file was developed to successfully call genotypes for 206,652 of the variants. Among these, 173,609 variants were variable and genotyped with a call rate of at least 90% in all 18,271 individuals. Among these were 82,979 variants predicted to change the amino acid structure of encoded proteins. To identify variants as candidates for early embryonic lethals, we first determined those for which no homozygotes were found for one of the homozygote classes. This identified 28,193 loci in Angus cattle, however, 92% of these had allele frequencies of ≤1% indicating that the sample size was insufficient to detect homozygotes should they be viable. Of the 2,224 loci for which homozygotes were expected to have been observed, many clustered into regions of the genome harboring gene families, including olfactory receptors, the major histocompatibility complex and the pregnancy associated glycoproteins suggesting that the assay may be detecting segregating copy number variants rather than genic SNP. The next phase of the project is to identify loci within single copy genes that are predicted to be essential for life to identify candidates for early embryonic lethals in beef cattle.