Genomic partition of inbreeding depression in production traits of US Jersey cattle using functional annotations

Inbreeding depression (InD) refers to the mean reduction in trait values due to inbreeding, with detrimental effects on survival, production, and reproduction traits that have been observed in many natural and domesticated populations. Despite efforts to measure how much reduction in the traits of interest was caused by InD, the genetic and molecular basis of these declines remains unclear, particularly in dairy cattle. In this research, we used a linear mixed model to partition the InD of 3 production traits in 245,517 genotyped Jersey cows from the Council on Dairy Cattle Breeding (Bowie, MD) database. We mapped 9,532,696 imputed sequence variants into 5 functional annotation categories (i.e., intron, promoter, genomic evolutionary rate profiling [GERP] constrained elements, coding sequence, untranslated regions [UTR], and remaining). We estimated the effects of InD attributed to each functional annotation category by a mixed model method accounting for additive effects and relatedness through a genomic relationship matrix. The InD for milk yield was significantly enriched for promoter regions (enrichment ratio [R_k] = 20.11, SE = 6.44), UTR regions (R_k = 57.96, SE = 16.62) and GERP regions (R_k = 35.91, SE = 7.00). The enrichment ratio R_k represents the disproportionate effect that annotation-specific homozygosity has on the trait mean compared with the magnitude of InD on the whole-genome level. Similarly, protein yield showed significant enrichment of InD for promoter regions (R_k = 15.25, SE = 5.45), UTR regions (R_k = 46.44, SE = 14.07), and GERP regions (R_k = 32.73, SE = 5.92), whereas fat yield showed significant enrichment of InD for UTR regions (R_k = 40.20, SE = 12.77) and GERP regions (R_k = 28.72, SE = 5.34). Our results indicate that certain functional annotations in dairy cattle genome are disproportionally responsible for the detrimental effects of inbreeding, which could be vulnerable to deleterious mutations. This research can help better elucidate the genetic and molecular basis of InD in dairy cattle genome and potentially guide breeding strategies for genomic selection.