|Smith, Timothy - Tim|
|Thallman, Richard - Mark|
|Kalbfleisch, Ted - UNIVERSITY OF LOUISVILLE|
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/29/2015
Publication Date: 11/1/2015
Citation: Snelling, W.M., Bennett, G.L., Keele, J.W., Kuehn, L.A., McDaneld, T.G., Smith, T.P., Thallman, R.M., Kalbfleisch, T.S., Pollak, E.J. 2015. A survey of polymorphisms detected from sequences of popular beef breeds. Journal of Animal Science. 93(11):5128-5143. doi:10.2527/jas2015-9356.
Interpretive Summary: As part of an effort to identify DNA sequence variation that affects beef cattle performance, DNA from 270 influential bulls in the U.S. Meat Animal Research Center Germplasm Evaluation (GPE) project was sequenced. The bulls included 154 purebred sires sampled from the most popular breeds in the U.S. (Angus, Hereford, Simmental, Limousin, Charolais, Gelbvieh and Red Angus), 83 crossbred sons of those bulls which were used as natural service sires in GPE, and 33 purebred bulls from other breeds that conduct national cattle evaluations. Whole-genome sequence was obtained from all bulls, and exome sequence, which targeted protein-coding genes, was obtained from 176 bulls. Nearly 30 million different variations in DNA sequence were detected, but less than 1% of the detected variation occurred in protein-coding genes. About one-third of the variation in gene sequence was detected in bulls from all seven predominant breeds, and less than 5% was detected only in bulls from one of the seven breeds. A larger than expected number of genes involved in immune system processes and immune response were affected by commonly observed variation. The coding sequence variants tended to have low minor allele frequencies, in contrast to high minor allele frequencies of single nucleotide polymorphisms selected for commercially available whole-genome genotyping assays. Further investigation is needed to assess how much influence coding sequence variants identified from this work might have on cattle performance.
Technical Abstract: Genome sequence was obtained from 270 sires used in the Germplasm Evaluation project (GPE). These bulls included 154 purebred AI sires from GPE Cycle VII breeds (Hereford, Angus, Simmental, Limousin, Charolais, Gelbvieh, Red Angus), 83 F1 crosses of those breeds, and 33 AI sires from 8 other breeds. Exome capture sequence targeting coding regions of the genome was obtained from 176 of these bulls. Sequence reads were mapped to the UMD 3.1 bovine genome assembly; a mean of 2.5-fold (x) coverage per bull was obtained from the genomic sequence, and the targeted exons were covered at a mean of 20.0x. Over 28.8 million biallelic sequence variants were detected where each allele was present in at least three different bulls. These included 22.0 million previously reported variants, and 94.1% of the 774,660 autosomal and BTA X SNP on the BovineHD BeadChip assay (HD). 92.2% of the variants detected in targeted exons were also detected from just the low-coverage genome sequence. Less than 1% of the variants detected occurred in annotated protein coding sequence or 5’ and 3’ untranslated regions (UTR) flanking the 19,994 annotated protein coding genes. Variation was detected in coding sequence or UTR of 96.8% of the genes: loss-of-function variants were predicted for 3,298 genes; 14,973 contained non-synonymous variants, 11,276 had variation in UTR, and 17,721 genes contained synonymous variants. Minor allele frequencies (MAF) were < 0.05 for 47.8% of the coding sequence and UTR variants, and MAF distributions were skewed towards low MAF. In contrast, 11.1% of the HD SNP detected in these bulls had MAF < 0.05, and the distribution was skewed towards higher MAF. Genes involved in immune system processes and immune response were overrepresented among those genes containing loss-of-function and non-synonymous polymorphisms.