Location: Animal Genomics and Improvement Laboratory
Project Number: 8042-31000-113-013-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Jun 1, 2020
End Date: May 31, 2023
Declining fertility in dairy cattle is a serious threat to the profitability of dairy cattle. Fertility is one of the traits affected most by crossbreeding. The discovery of genetic variants and their mechanism underlying reproductive heterosis will facilitate developing new strategies to improve dairy fertility. This proposed research is the first attempt to understand reproductive heterosis in dairy cattle and aims at the discovery and utilization of genetic variants and mechanisms underlying dairy reproductive heterosis for genetic improvement of dairy fertility. Specific objectives supporting this overall objective include: 1) Detect chromosome regions and assessing genetic mechanism associated with reproductive heterosis using genome-wide association study (GWAS); 2) Fine-map and identify candidate causal variants underlying reproductive heterosis by an integrated analysis of comparative genomics, and 3) Improve Holstein using heterosis variants and mechanisms. This research will yield a list of genome variants associated reproductive heterosis and their specific effects potentially including additive, dominance and epistasis effects, verification and fine mapping 3 million SNPs from the sequence data of hypothetical Holstein x Jersey crosses, functional relevance from mouse comparative analysis and from comparative analysis of genetic selection in Holstein cattle since 1964. The total contribution of all heterosis variants as well as the total contribution of candidate variants for gene editing will be estimated. The results from this research will be a significant contribution to the scientific understanding of reproductive heterosis in dairy cattle and to the genetic improvement of dairy fertility utilizing heterosis variants and mechanisms.
Aim 1: Detect chromosome regions and assessing genetic mechanism associated with reproductive heterosis using genome-wide association study (GWAS). The GWAS analysis will identify chromosome regions and genetic variants with significant effects on the fertility traits in the crossbreeding population. Assessment of genetic mechanism is achieved by testing the significance of additive and dominance of each SNP, and epistasis effect of each pair of SNPs. For SNPs with significant dominance effects, we will further assess whether the dominance effects were incomplete dominance or overdominance. For epistasis effects, we will determine the exact type of the epistasis effects. Aim 2: Fine map and identify candidate causal variants underlying reproductive heterosis by an integrated analysis of comparative genomics. This analysis will verify heterosis variants from GWAS, find other variants potentially associated with reproductive heterosis using frequency comparison based on sequence data, and investigate functional relevance of heterosis variants to fertility by comparison with mouse knockout genes affecting fertility and chromosome regions affected by genetic selection since 1964. Candidate variants associated with reproductive heterosis will be identified and their contribution to heterosis evaluated. Aim 3: Explorative study of using heterosis variants and mechanisms to improve Holstein fertility, and to predict optimal mating to maximize reproductive heterosis. SNP effects from crossbreds representing fertility heterosis will be added to the mixed model for genomic prediction of fertility traits in Holsteins, and the accuracy change due to crossbred SNP effects will be evaluated using validation studies.