PSII-1 Genomic study for pregnancy loss in Brahman cattle.

Abstract Reproduction is a key determinant of efficiency and economic sustainability in beef cattle operations, as it directly influences calf production. In beef herds, where reproductive management is generally less intensive than in dairy systems, many pregnancy losses (PL) go undetected, making it challenging to identify their underlying causes. Understanding the genetic basis of PL is crucial for enhancing reproductive success and improving breeding strategies. The objective of this study was to estimate variance components and investigate genetic factors associated with PL in Brahman cattle. Phenotypic records consisted of 29,905 pregnancy and abortion records from nulliparous, primiparous, and multiparous cows raised in two herds in Bolivia between 1998 and 2021. Both herds followed reproductive disease prevention protocols. Pregnancy was confirmed by rectal palpation approximately 60 days after the breeding season ended, based on cows not returning to heat. Cows with successful pregnancies were assigned a phenotype of 1, while cows experiencing pregnancy loss were assigned a phenotype of 2. A total of 921 animals were genotyped using a medium-density SNP chip (~52K markers). Variance components were estimated using a threshold repeatability model to assess the binary response to PL through a single-step genomic BLUP procedure. SNP quality control excluded markers with unknown positions, those on sex chromosomes, MAF < 0.05, Hardy-Weinberg disequilibrium (P < 10⁻⁶), low call rates (< 90%), and excess heterozygosity. Genomic regions and candidate genes were identified based on the percentage of genetic variance explained by 10 adjacent SNP across the entire bovine genome. The Ensembl Biomart tool with the Genes 113 database and bovine genome ARS-UCD1.3 dataset was used to identify the gene content of genomic regions. Orthologous genes had their functions investigated in MeSH (Medical Subject Headings), OMIM and OMIA. Orthologous genes were also identified in humans (H. sapiens), rats (R. norvegicus), and mice (M. musculus). The heritability estimate for PL was low (0.114), but the presence of genetic variance suggests that selection for improved reproductive performance is feasible. Genome-wide association analyses identified 17 candidate regions in 12 chromosomes containing 92 genes. CDC40 (BTA9) is involved in pre-mRNA splicing and cell cycle regulation, with potential links to reproductive inefficiencies. DIS3 (BTA12) plays a crucial role in RNA metabolism, and its mutations are associated with embryonic lethality and infertility. MKS1 (BTA19) is essential for ciliogenesis, with mutations linked to severe congenital abnormalities and early embryonic death. The candidate regions reported in this study provide insights into the genetic architecture of PL for identifying and selecting animals with improved reproductive performance, ultimately enhancing the productivity of Brahman cattle. Moreover, our findings contribute to a better understanding of the genetic and physiological mechanisms underlying pregnancy retention in beef cattle.