Genetic variations of bovine PCOS-related DENND1A gene identified in GWAS significantly affect female reproductive traits.

Genome-wide association studies (GWAS) have identified DENND1A as a potential candidate gene linked to the fertility-related phenotypes in dairy cows. However, to date, no studies have examined the association of the DENND1A insertion/deletions (indels) to bovine fertility on a large scale. Herein, two indel sites, including P4-del-26-bp and P8-ins-15-bp were identified in 1064 Holstein cows. The values of the minor allelic frequency (MAF) ranged between 0.471 (deletion) and 0.230 (deletion), respectively, and combined four different haplotypes by analyzing the haplotype combination. It is noteworthy that P4-del-26-bp is associated with the ovarian width (P = 0.0004) and corpus luteum diameter (P = 0.004). Meanwhile, P8-ins-15-bp was found to have a significant association with the ovarian width (P = 0.020), ovarian weight (P = 0.004), the number of mature follicles (P = 0.020), and diameter of the mature follicles (P = 0.016). Furthermore, the combinatorial analysis showed that the two indel combined-genotypes were significantly related to several reproductive traits (ovarian width, ovarian weight, etc.). Collectively, our findings indicated that these two novel indels and their combinations are correlated with the reproductive traits, and hence, they can serve in the marker-assisted selection (MAS) in cattle breeding. Nevertheless, further functional experiments are needed for understanding the mechanisms of these indels in cattle reproduction in a better way.