Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/28/2014
Publication Date: 5/1/2014
Publication URL: http://aipl.arsusda.gov/publish/jds/2014/97_3156.pdf
Citation: Cole, J.B., Waurich, B., Wensch-Dorendorf, M., Bickhart, D.M., Swalve, H.H. 2014. A genome-wide association study of calf birth weight in Holstein cattle using single nucleotide polymorphisms and phenotypes predicted from auxiliary traits. Journal of Dairy Science. 97(5):3156-3172. Interpretive Summary: Earlier research by this laboratory identified a region of chromosome 18 in Holstein cattle that affects several important traits, including the difficulty with which calves are born and the lifetime profitability of dairy cows. The biological mechanism causing that effect is not yet understood, but it may be due to calves with high birth weights. Dairy farmers in the U.S. do not routinely record birth weights, so we worked with colleagues in Germany, where birth weights are measured and production systems are similar to those in the U.S., to develop an equation for the prediction of calf birth weights. Analysis of the predicted birth weights identified several regions of the genome that have large effects on birth weight, and many of those areas include genes that are involved in growth and development. These results will help us identify the biological mechanism(s) associated with chromosome 18. Once the causal locus has been determined it can be used in breeding programs to avoid the harmful economic impacts associated with this region of the cattle genome.
Technical Abstract: Previous research has found that there is a QTL affecting calving and conformation traits on Bos taurus (BTA) autosome 18 that may be related to increased calf birth weights, which are not routinely recorded in the US. Birth weight (BW) data from large, intensively managed dairies in eastern Germany with management systems similar to those commonly found in the US were used to develop a selection index predictor for PTA of BW. The predictor included body depth, rump width, sire calving ease, sire gestation length, sire stillbirth, stature, and strength. Genetic and phenotypic correlations and heritabilities from the US were substituted for the German values, and BW PTA predicted for 31,984 bulls with US genetic evaluations. A genomewide association study was conducted using a Bayes A model to predict allele substitution effects for 43,188 single nucleotide polymorphisms (SNP). Genotypes were available for 204,618 animals, including 53,644 predictor animals. Gene set enrichment analysis (GSEA) was performed on the 100 SNP that had the largest effects expressed in additive genetic standard deviations. Several SNP related to growth and development were found among the 25 SNP with the largest effects, including ABCA12, FLRT2, LHX4, MAP3K5, NRAC, NTNG1, PIGN, and ZNF75A. The GSEA identified the Kyoto Encyclopedia of Genes and Genomes “Regulation of actin cytoskeleton” pathway (bta04810) as being enriched. That pathway includes the ROCK gene, which is involved in placental function in the human, as well as other developmental genes (e.g., FAK and PAK). These results suggest that prediction equations derived from one population may be useful for identifying genes and gene networks associated with phenotypes that are not directly measured in a second population.