|Cushman, Robert - Bob|
|Thallman, Richard - Mark|
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/21/2011
Publication Date: 4/1/2012
Publication URL: http://handle.nal.usda.gov/10113/55207
Citation: Snelling, W.M., Cushman, R.A., Fortes, M., Reverter, A., Bennett, G.L., Keele, J.W., Kuehn, L.A., McDaneld, T.G., Thallman, R.M., Thomas, M.G. 2012. How single nucleotide polymorphism chips will advance our knowledge of factors controlling puberty and aid in selecting replacement beef females. Journal of Animal Science. 90:1152-1165. Interpretive Summary: Genomic selection promises to accurately predict genetic merit for heifer fertility, using simple DNA tests to replace low accuracy predictions using pedigree and expensive or inconvenient measurements to indicate genetic potential for puberty and pregnancy in heifers. Knowing which genes and DNA mutations cause variation in puberty and pregnancy is the best way to fulfill the promise of accurately predicting genetic potential from DNA. So far, studies examining approximately 50,000 DNA markers along the genome of hundreds of heifers have failed to conclusively identify specific genes or regions of the genome that affect puberty or pregnancy. Very expensive studies, examining tens to hundreds of thousands of heifers with ten times as many markers, that are much closer together, will have better chances of finding specific genes and mutations that definitely affect heifer fertility. Pooling DNA from heifers according to pregnancy status or early and late puberty can substantially reduce genotyping costs while maintaining power to detect meaningful effects. Information about effects on growth and body compsition traits, which are correlated with puberty and fertility, as well as knowledge about gene function, expression and interactions can focus the search on genes and regulatory regions most likely to affect fertility. Integrating functional gene networks with associations between genotypes and phenotypes for fertility and related traits may contribute to greater understanding of genomic factors affecting heifer puberty and pregnancy, with the ultimate goal of developing a cost-effective test to screen heifer calves for potential fertility.
Technical Abstract: The promise of genomic selection is accurate prediction of animals' genetic potential from their genotypes. Simple DNA tests might replace low accuracy predictions for expensive or lowly heritable measures of puberty and fertility based on performance and pedigree. Knowing which DNA variants affect puberty and fertility with some certainty is the best way to fulfill the promise. Several single nucleotide polymorphisms (SNP) from the BovineSNP50 assay have tentatively been associated with age at puberty, antral follicle count, pregnancy and related traits measured on different sets of heifers. However, sample sizes are too small and SNP density too sparse to definitively correlate SNP with causal genomic variants affecting reproductive success. Associations between individual SNP and similar phenotypes are inconsistent across data sets, and genomic predictions do not appear applicable to unrelated cattle. Discrepancies may be a result of different quantitative trait loci (QTL) segregating in the sampled populations, differences in linkage disequilibrium (LD) patterns so the same SNP are not correlated with the same QTL, and spurious correlations with phenotype. A number of approches can be used independently, or in combination, to improve detection of genomic factors affecting heifer puberty and fertility. Larger samples and denser SNP will increase power to detect real associations with SNP having more consistent LD with underlying QTL. Meta-analysis combining results from different studies will effectively increase sample size. High-density genotyping with heifers pooled by pregnancy status, or early and late puberty can be a cost-effective means to sample large numbers. Additionally, networks of genes, implicated by associations with multiple traits correlated with puberty and fertility, could provide insight into the complex nature of these traits, especially if corroborated by functional annotation, established gene interaction pathways, and transcript expression. Integrating information about gene function and regulation with statistical associations from whole-genome SNP genotyping assays will enhance knowledge of genomic mechanisms affecting puberty, enabling development of more reliable DNA tests to guide heifer selection decisions.