Gene function & annotation

Identification of Potential Recessive Lethal Haplotypes in Five Irish Sheep Breeds

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Abstract

Recessive lethal mutations are known contributor to poor reproductive performance in livestock due to embryonic or foetal death in homozygous individuals. Although several recessive alleles have been identified in cattle and pig populations, fewer studies have been undertaken in sheep. The objective of this study is to identify potential recessive lethal haplotypes in five Irish sheep breeds. Genotype data were available for 45,653 pure-breed sheep, 16,867 Texel, 10,084 Charollais, 7,878 Suffolk, 7,474 Belclare and 3,350 Vendeen from a variety of panels. All genotype panels were imputed to Ovine SNP50 density and haplotypes were phased using FImpute V2.2. After edits, 48,450 single nucleotide polymorphisms (SNPs) remained. A default haplotype window length of 10 SNPs was selected for the present study (~0.5Mb). For each of these haplotypes, the expected frequency of homozygous individuals within breed was calculated using one of two methods: (1) based on the haplotype frequency in the population, assuming random mating. The expected haplotype frequency equals the population size divided by 4 and multiplied by the carrier haplotype frequency squared, (2) based on sire-dam-progeny trios, by summing the probabilities that both parents transmit the haplotype to each offspring multiplied by the number of progeny per sire-dam pair. The probability of observing the number of homozygotes given the expected count for each haplotype was estimated using the Poisson distribution. A haplotype was considered significantly deficient in homozygotes when the p-value was lower than 1x10-6. Consecutive significantly deficient haplotypes that shared the same allele and observed carrier frequency (adjusting for the single-SNP sliding window) were combined into a single haplotype. Putative lethal haplotypes were defined as significantly deficient haplotypes that were never observed in the homozygous state. Using the population-based method, a total of 619 significantly deficient haplotypes were identified across breed. Overlapping genomic regions (i.e. different haplotypes at the same genomic position) within and across breed were observed, resulting in 56 unique genomic regions; 29 of which had shown at least one potential lethal haplotype. Using the trio-based method, 527 significantly deficient haplotypes were observed across breed, corresponding to 71 unique genomic regions, 30 had shown at least one potential lethal haplotype. In total 35 unique genomic regions across both methods revealed at least one putative lethal haplotype. Some genes of interest within these regions include BOLA3 (OAR22), which is linked to mitochondrial disease in humans; KNL1 (OAR13), BRCA1 (OAR11) and RAD51 (OAR7), which have been associated with early embryonic loss in studies in mice. Overall, these results identify 35 genomic regions containing putative lethal haplotypes across five Irish sheep breeds. Further validation and targeted investigations to identify causal mutations and associations with fertility are required to quantify their contribution to reproductive loss and to inform breeding strategies.

Keywords: 2026

How to Cite:

Carthy, T., McHugh, N., Berry, D., Pabiou, T., McAuley, R. & Purfield, D., (2026) “Identification of Potential Recessive Lethal Haplotypes in Five Irish Sheep Breeds”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2286366. doi: https://doi.org/10.31274/wcgalp.23961

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