The detection of putative recessive lethal haplotypes in Irish sheep populations

In livestock populations, recessive lethal alleles are a known contributor to poor reproductive performance due to embryonic death in homozygous individuals. Despite their lethal effect, these alleles may be maintained at high frequencies among carrier animals because of their positive pleiotropic effects on economically important traits. Genotype data for 28,965 animals from five major Irish sheep breeds genotyped on a variety of panels were available. Only animals and single nucleotide polymorphisms (SNPs) with a call rate >90%, and a minor allele frequency >0.01 were retained. Non-autosomal SNPs and SNPs that did not adhere to Mendelian inheritance patterns were discarded. Haplotype phasing and genotype imputation of all panels to the Ovine SNP50 density was completed using FImpute V2.2. Following imputation, 43,951 SNPs remained across 28,945 pedigree animals, which included 11,268 verified progeny-sire-dam and 2,660 verified progeny-sire-maternal grandsire trios. To identify haplotypes with homozygous deficiency, a sliding haplotype window of 10 SNPs was used the scan the genome of all genotyped animals. A window of 10 SNPs was chosen due to the high level of haplotype diversity with homozygosity rates above 0.05. Haplotype lethality was determined using a chi-square test between the number of observed and expected haplotypes. A number of haplotypes showed a significant deficiency of homozygote animals across the five populations. For example, one candidate haplotype in the Belclare population was observed in the homozygous form significantly less than was expected (p<1×10-10). These findings can be incorporated into Irish sheep breeding programs to avoid carrier-by-carrier matings to reduce lamb mortality.