A genome scan for quantitative trait loci influencing carcass, post-natal growth and reproductive traits in commercial Angus cattle.

To gain insight into the number of loci of large effect that underlie variation in cattle, a quantitative trait locus (QTL) scan for 14 economically important traits was performed in two commercial Angus populations using 390 microsatellites, 11 single nucleotide polymorphisms (SNPs) and one duplication loci. The first population comprised 1769 registered Angus bulls born between 1955 and 2003, with Expected Progeny Differences computed by the American Angus Association. The second comprised 38 half-sib families containing 1622 steers with six post-natal growth and carcass phenotypes. Linkage analysis was performed by half-sib least squares regression with gridqtl or Bayesian Markov chain Monte Carlo analysis of complex pedigrees with loki. Of the 673 detected QTL, only 118 have previously been reported, reflecting both the conservative approach to QTL reporting in the literature, and the more liberal approach taken in this study. From 33 to 71% of the genetic variance and 35 to 56% of the phenotypic variance in each trait was explained by the detected QTL. To analyse the effects of 11 SNPs and one duplication locus within candidate genes on each trait, a single marker analysis was performed by fitting an additive allele substitution model in both mapping populations. There were 53 associations detected between the SNP/duplication loci and traits with -log(10) P(nominal) ≥ 4.0, where each association explained 0.92% to 4.4% of the genetic variance and 0.01% to 1.86% of the phenotypic variance. Of these associations, only six SNP/duplication loci were located within 8 cM of a QTL peak for the trait, with two being located at the QTL peak: SST_DG156121:c.362A>G for ribeye muscle area and TG_X05380:c.422C>T for calving ease. Strong associations between several SNP/duplication loci and trait variation were obtained in the absence of any detected linked QTL. However, we reject the causality of several commercialized DNA tests, including an association between TG_X05380:c.422C>T and marbling in Angus cattle.

Genomic tools for characterizing monogenic and polygenic traits in ruminants--using the bovine as an example.

Next generation sequencing platforms have democratized genome sequencing. Large genome centers are no longer required to produce genome sequences costing millions. A few lanes of paired-end sequence on an Illumina Genome Analyzer, costing < $10,000, will produce more sequence than generated only a few years ago to produce the human and cow assemblies. The de novo assembly of large numbers of short reads into a high-quality whole-genome sequence is now technically feasible and will allow the whole genome sequencing and assembly of a broad spectrum of ruminant species. Next-generation sequencing instruments are also proving very useful for transcriptome or resequencing projects in which the entire RNA population produced by a tissue, or the entire genomes of individual animals are sequenced, and the produced reads are aligned to a reference assembly. We have used this strategy to examine gene expression differences in tissues from cattle differing in feed efficiency, to perform genome-wide single nucleotide polymorphism discovery for the construction of ultrahigh-density genotyping assays, and in combination with genome-wide association analysis, for the identification of mutations responsible for Mendelian diseases. The new 800K SNP bovine genotyping assays possess the resolution to map trait associations to the locations of individual genes and the 45 million polymorphisms identified in > 180X genome sequence coverage on over 200 animals can be queried to identify the polymorphisms present within positional candidate genes. These new tools should rapidly allow the identification of genes and mutations underlying variation in cattle production and reproductive traits.