Gene mapping and genomic prediction of bull fertility using sex chromosome markers.

Discipline: genomic selection; Keywords: genomic prediction, pseudo-autosomal region, sire conception rate, X chromosome.

Successful reproductive performance is the basis for profitable dairy farming. Poor reproductive performance results in increased calving intervals and decreased milk production, and therefore significant economic losses to the farmer. Considering its relevance, dedicated efforts have been made to improve fertility traits and worldwide  cow fertility in dairy herds has improved in the past two decades due to improvements in nutrition and management, the development of reproductive management tools such as ovulation synchronization and, more recently, the incorporation of reproductive traits into breeding programs. The adoption of genomic selection in the last 10 years has resulted in a remarkable increase in annual genetic gains for low heritable traits, including cow fertility.

Although both parents affect reproductive success, much of the research on dairy cattle has focussed on cow fertility and the potential contribution of the bull has been somewhat ignored. Nevertheless, recent studies have shown that sire factors directly contribute to pregnancy success. Indeed, there is growing evidence that the reduced ability of low-fertility bulls to establish pregnancy is multi-factorial, including sperm fertilizing ability, pre-implantation embryonic development, and placenta and embryo development. Geneticists working in this area have been investigating potential genetic factors underlying this variation in sire fertility. They have identified candidate genomic regions, individual genes, biological processes and molecular mechanisms controlling dairy bull fertility. They have also reported promising results for predicting sire conception rate values using genomic data. It should be noted that all of these studies have investigated genetic variants on autosomal chromosomes. Little is known about the potential contributions of sex chromosomes to dairy bull fertility. The bovine X and Y chromosomes (BTAX and BTAY, respectively) have two distinct regions: (1) the pseudo-autosomal region (PAR), which is the recombination region between the two chromosomes and behaves like an autosome chromosome, recombining during meiosis, and therefore has an essential role in meiotic pairing and male fertility; and (2), the X- and Y-specific regions that are unpaired.

The main goal of the study by Dr H. A. Pacheco and co-workers was to reveal the genetic contribution of sex chromosomes on sire conception rate in Holstein dairy cattle.  Their results were published in the Journal of Dairy Science, Volume 103, page 3304 to 3311. The title of the paper was: Gene mapping and genomic prediction of bull fertility using sex chromosome markers. 

The researchers first performed genomic scans of BTAX and BTAY to identify the relevant genetic variants associated with sire fertility. The relevance of the SNP located on the PAR, X-specific, and Y-specific regions was investigated. Secondly, they investigated the benefits of including sex chromosome markers in alternative genomic prediction models for sire fertility. The analysis included a total of 5014 bulls with sire conception rate records and genotypes for roughly the 291k SNP located on the autosomes, the 1.5k SNP located on the pseudo-autosomal region (PAR), the 13.7k BTAX-specific SNP, and the 24 BTAY-specific SNP. Initially, genomic scans of the sex chromosomes were performed, and thereafter the genomic prediction of sire conception rate was evaluated. The BTAX SNP markers in the predictive models were included in the analysis.

Two markers located on PAR and three markers located on the X-specific region showed significant associations with sire fertility. Interestingly, these regions harbour genes, such as FAM9B, TBL1X, and PIH1D3, which are directly implicated in testosterone concentration, spermatogenesis and sperm motility. BTAY, however, showed very low genetic variability, and none of the segregating markers were associated with sire conception rate. Notably, the model predictive ability was largely improved by including BTAX markers; the combination of autosomal with the BTAX SNP delivered predictive correlations around 0.343, representing an increase in accuracy of about 7.5% compared with the standard whole autosomal genome approach. 

Overall, this study provides evidence of the importance of both PAR and X-specific regions in male fertility in dairy cattle. These findings may help to improve conception rates in dairy herds through more accurate genome-based decisions on bull fertility.