PSII-3 Candidate lethal haplotypes associated with functional longevity in Angus cattle.

Abstract Reproductive traits directly impact productivity, profitability, and sustainability in beef cattle production system. Longevity plays a critical role, as it reflects a female’s ability to remain in the herd while maintaining consistent reproductive performance. The presence of deleterious recessive alleles can lead to reduced economic performance. While mortality is an easy phenotype to score, reduced reproductive performance due to genetics is not as easy to detect. The objective of this study was to identify potential lethal haplotypes and investigate their association with functional longevity (FL) in Angus cattle. A total of 2,540,901 animals was included in the pedigree, of which 1,439,172 were genotyped with 54,609 SNP markers. Phenotypic records were available for 63,813 cows. Reduced homozygosity was used as a criterion to identify potential lethal haplotypes considering window size from 2 to 20 SNPs and analyzing trios and parent-grandparent relationships. Functional longevity was defined as the total number of calves a cow has produced up to six years of age. A linear single-step genomic BLUP (ssGBLUP) model was used to estimate the genomic breeding values. The model accounted for the animal random effect and the fixed effects of embryo transfer status, contemporary group (herd, year and season of birth) and calving year-season. A total of 1,889 haplotypes had significantly lower heterozygosity within population and were labeled as candidate lethal haplotypes. Then, a genome wide association study was performed with the haplotypes as pseudo-SNPs for 21,681 cows that had phenotypes and haplotype information available. Out of those 1,889 haplotypes, a total of 15 regions across 5 chromosomes explained more than 1% of the additive genetic variance of FL. Haplotypes on BTA8 (1 region), BTA9 (1 region), BTA7 (3 regions), BTA28 (3 regions), and BTA21 (7 regions) explaining up to 3% of the variance of FL. These regions harbors genes related to ovarian-insufficiency, bone-marrow failure, and male subfertility in humans and mice, and growth in cattle. The gene SAXO2 on BTA21 specifically, was found to negatively impact pregnancy outcome of beef heifers submitted to artificial insemination. These 15 potentially lethal haplotypes serve as an initial foundation for understanding the genetic architecture of FL in Angus population, providing a basis for further investigation to validate these candidate regions.