Whole-genome homozygosity mapping reveals candidate regions affecting bull fertility in US Holstein cattle.

BACKGROUND: Achieving rapid genetic progress while maintaining adequate genetic diversity is one of the main challenges facing the dairy industry. The increase in inbreeding can be used to monitor the loss of genetic diversity. Inbreeding tends to increase the proportion of homozygous loci, some of which cause homozygosity of recessive alleles that results in reduced performance. This phenomenon is known as inbreeding depression and tends to be most prominent on fitness-related traits, such as male fertility. Traditionally, inbreeding has been monitored using pedigree information, or more recently, genomic data. Alternatively, it can be quantified using runs of homozygosity (ROH), i.e., contiguous lengths of homozygous genotypes observed in an individual's chromosome. RESULTS: The objective of this study was to evaluate the association between ROH and sire conception rate. ROH were evaluated using 268 k genetic markers in 11,790 US Holstein bulls. Interestingly, either the sum, mean, or maximum length of ROH were negatively associated with bull fertility. The association analysis between ROH and sire fertility was performed comparing 300 high-fertility vs. 300 low-fertility bulls. Both the average and sum of ROH length were higher in the low-fertility group. The enrichment of ROH regions in bulls with low fertility was assessed using a Fisher's exact test. Nine regions were significantly enriched in low-fertility compared to high-fertility bulls. Notably, these regions harbor genes that are closely related to sperm biology and male fertility, including genes exclusively or highly expressed in testis. CONCLUSIONS: The results of this study can help not only to manage inbreeding in genomic selection programs by designing custom mating schemes, but also to better understand the mechanisms underlying male fertility in dairy cattle.

Predicting male fertility in dairy cattle using markers with large effect and functional annotation data.

BACKGROUND: Fertility is among the most important economic traits in dairy cattle. Genomic prediction for cow fertility has received much attention in the last decade, while bull fertility has been largely overlooked. The goal of this study was to assess genomic prediction of dairy bull fertility using markers with large effect and functional annotation data. Sire conception rate (SCR) was used as a measure of service sire fertility. Dataset consisted of 11.5 k U.S. Holstein bulls with SCR records and about 300 k single nucleotide polymorphism (SNP) markers. The analyses included the use of both single-kernel and multi-kernel predictive models fitting either all SNPs, markers with large effect, or markers with presumed functional roles, such as non-synonymous, synonymous, or non-coding regulatory variants. RESULTS: The entire set of SNPs yielded predictive correlations of 0.340. Five markers located on chromosomes BTA8, BTA9, BTA13, BTA17, and BTA27 showed marked dominance effects. Interestingly, the inclusion of these five major markers as fixed effects in the predictive models increased predictive correlations to 0.403, representing an increase in accuracy of about 19% compared with the standard model. Single-kernel models fitting functional SNP classes outperformed their counterparts using random sets of SNPs, suggesting that the predictive power of these functional variants is driven in part by their biological roles. Multi-kernel models fitting all the functional SNP classes together with the five major markers exhibited predictive correlations around 0.405. CONCLUSIONS: The inclusion of markers with large effect markedly improved the prediction of dairy sire fertility. Functional variants exhibited higher predictive ability than random variants, but did not outperform the standard whole-genome approach. This research is the foundation for the development of novel strategies that could help the dairy industry make accurate genome-guided selection decisions on service sire fertility.

Genomic prediction of bull fertility in US Jersey dairy cattle.

Service sire has a major effect on reproductive success in dairy cattle. Recent studies have reported accurate predictions for Holstein bull fertility using genomic data. The objective of this study was to assess the feasibility of genomic prediction of sire conception rate (SCR) in US Jersey cattle using alternative predictive models. Data set consisted of 1.5k Jersey bulls with SCR records and 95k SNP covering the entire genome. The analyses included the use of linear and Gaussian kernel-based models fitting either all the SNP or subsets of markers with presumed functional roles, such as SNP significantly associated with SCR or SNP located within or close to annotated genes. Model predictive ability was evaluated using 5-fold cross-validation with 10 replicates. The entire SNP set exhibited predictive correlations around 0.30. Interestingly, either SNP marginally associated with SCR or genic SNP achieved higher predictive abilities than their counterparts using random sets of SNP. Among alternative SNP subsets, Gaussian kernel models fitting significant SNP achieved the best performance with increases in predictive correlation up to 7% compared with the standard whole-genome approach. Notably, the use of a multi-breed reference population including the entire US Holstein SCR data set (11.5k bulls) allowed us to achieve predictive correlations up to 0.315, gaining 8% in accuracy compared with the standard model fitting a pure Jersey reference set. Overall, our findings indicate that genomic prediction of Jersey bull fertility is feasible. The use of Gaussian kernels fitting markers with relevant roles and the inclusion of Holstein records in the training set seem to be promising alternatives to the standard whole-genome approach. These results have the potential to help the dairy industry improve US Jersey sire fertility through accurate genome-guided decisions.

Single nucleotide polymorphisms in candidate genes associated with milk yield in Argentinean Holstein and Holstein x Jersey cows.

BACKGROUND: Research on loci influencing milk production traits of dairy cattle is one of the main topics of investigation in livestock. Many genomic regions and polymorphisms associated with dairy production have been reported worldwide. In this context, the purpose of this study was to identify candidate loci associated with milk yield in Argentinean dairy cattle. A database of candidate genes and single nucleotide polymorphisms (SNPs) for milk production and composition was developed. Thirty-nine SNPs belonging to 22 candidate genes were genotyped on 1643 animals (Holstein and Holstein x Jersey). The genotypes obtained were subjected to association studies considering the whole population and discriminating the population by Holstein breed percentage. Phenotypic data consisted of milk production values recorded during the first lactation of 1156 Holstein and 462 Holstein x Jersey cows from 18 dairy farms located in the central dairy area of Argentina. From these records, 305-day cumulative milk production values were predicted. RESULTS: Eight SNPs (rs43375517, rs29004488, rs132812135, rs137651874, rs109191047, rs135164815, rs43706485, and rs41255693), located on six Bos taurus autosomes (BTA4, BTA6, BTA19, BTA20, BTA22, and BTA26), showed suggestive associations with 305-day cumulative milk production (under Benjamini-Hochberg procedure with a false discovery rate of 0.1). Two of those SNPs (rs43375517 and rs135164815) were significantly associated with milk production (Bonferroni adjusted p-values < 0.05) when considering the Holstein population. CONCLUSIONS: The results obtained are consistent with previously reported associations in other Holstein populations. Furthermore, the SNPs found to influence bovine milk production in this study may be used as possible candidate SNPs for marker-assisted selection programs in Argentinean dairy cattle.