Lethal Haplotype Detection and Characterization in Angus Population

Increasingly inbred population structures in artificially inseminated livestock species adversely impacts reproductive fitness. In beef cattle (Bos taurus), selective breeding has increased the frequency of several known segregating recessive polymorphisms that cause embryonic loss and has also increased identity by descent throughout the genome. By identifying haplotypes for which homozygotes are not observed despite a sufficient sample size considering haplotype frequency, developmentally lethal recessive loci can be localized without the observation of loss-associated phenotype (e.g., failure to implant, first trimester abortion). In this study, haplotypes were constructed for 3881 registered Angus individuals with 54545 SNP genotypes using findhap v2, which exploits the complex pedigree among individuals in this population. Haplotypes that were not observed in homozygous form in the population despite a high frequency and pedigree-based expectation of homozygous inheritance are candidates for harboring recessive lethal alleles. Of these genotyped individuals, 86 have been resequenced to an average 30× coverage to identify loss-of- function alleles genome-wide and have had variants called using a custom in-house developed pipeline. For any candidate haplotype found in these bulls, phased whole-genome genotypes will be used to identify the variants that are responsible for lethality. This will provide insight into the biological foundations of inbreeding depression and the genomic architecture of developmentally important genes in selectively bred populations. Selective breeding programs can utilize these detected lethal haplotypes and causal variants to reduce the negative impact of inbreeding on fertility and to maximize overall genetic gains.