• Web-based Tools for the Analysis of DNA Microarrays

      Geeleher, P.; Golden, A.; Hinde, J.; Morris, Dermot G. (Teagasc, 2008-01-01)
      DNA microarrays are widely used for gene expression profiling. Raw data resulting from microarray experiments, however, tends to be very noisy and there are many sources of technical variation and bias. This raw data needs to be quality assessed and interactively preprocessed to minimise variation before statistical analysis in order to achieve meaningful result. Therefore microarray analysis requires a combination of visualisation and statistical tools, which vary depending on what microarray platform or experimental design is used.Bioconductor is an existing open source software project that attempts to facilitate analysis of genomic data. It is a collection of packages for the statistical programming language R. Bioconductor is particularly useful in analyzing microarray experiments. The problem is that the R programming language’s command line interface is intimidating to many users who do not have a strong background in computing. This often leads to a situation where biologists will resort to using commercial software which often uses antiquated and much less effective statistical techniques, as well as being expensively priced. This project aims to bridge this gap by providing a user friendly web-based interface to the cutting edge statistical techniques of Bioconductor.
    • Whole genome association study identifies regions of the bovine genome and biological pathways involved in carcass trait performance in Holstein-Friesian cattle

      Doran, Anthony G.; Berry, Donagh P.; Creevy, Christopher J.; Department of Agriculture, Food and the Marine; Teagasc Walsh Fellowship Programme; Science Foundation Ireland; Irish Cattle Breeding Federation; RSF-06-0353; 11/S/112; 2009183; 07/SK/B1236A (Biomed Central, 2014-10)
      Background Four traits related to carcass performance have been identified as economically important in beef production: carcass weight, carcass fat, carcass conformation of progeny and cull cow carcass weight. Although Holstein-Friesian cattle are primarily utilized for milk production, they are also an important source of meat for beef production and export. Because of this, there is great interest in understanding the underlying genomic structure influencing these traits. Several genome-wide association studies have identified regions of the bovine genome associated with growth or carcass traits, however, little is known about the mechanisms or underlying biological pathways involved. This study aims to detect regions of the bovine genome associated with carcass performance traits (employing a panel of 54,001 SNPs) using measures of genetic merit (as predicted transmitting abilities) for 5,705 Irish Holstein-Friesian animals. Candidate genes and biological pathways were then identified for each trait under investigation. Results Following adjustment for false discovery (q-value < 0.05), 479 quantitative trait loci (QTL) were associated with at least one of the four carcass traits using a single SNP regression approach. Using a Bayesian approach, 46 QTL were associated (posterior probability > 0.5) with at least one of the four traits. In total, 557 unique bovine genes, which mapped to 426 human orthologs, were within 500kbs of QTL found associated with a trait using the Bayesian approach. Using this information, 24 significantly over-represented pathways were identified across all traits. The most significantly over-represented biological pathway was the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Conclusions A large number of genomic regions putatively associated with bovine carcass traits were detected using two different statistical approaches. Notably, several significant associations were detected in close proximity to genes with a known role in animal growth such as glucagon and leptin. Several biological pathways, including PPAR signaling, were shown to be involved in various aspects of bovine carcass performance. These core genes and biological processes may form the foundation for further investigation to identify causative mutations involved in each trait. Results reported here support previous findings suggesting conservation of key biological processes involved in growth and metabolism.
    • Within- and across-breed imputation of high-density genotypes in dairy and beef cattle from medium- and low-density genotypes

      Berry, Donagh P.; McClure, M.C.; Mullen, M.P. (Wiley, 2013-12-05)
      The objective of this study was to evaluate, using three different genotype density panels, the accuracy of imputation from lower- to higher-density genotypes in dairy and beef cattle. High-density genotypes consisting of 777 962 single-nucleotide polymorphisms (SNP) were available on 3122 animals comprised of 269, 196, 710, 234, 719, 730 and 264 Angus, Belgian Blue, Charolais, Hereford, Holstein-Friesian, Limousin and Simmental bulls, respectively. Three different genotype densities were generated: low density (LD; 6501 autosomal SNPs), medium density (50K; 47 770 autosomal SNPs) and high density (HD; 735 151 autosomal SNPs). Imputation from lower- to higher-density genotype platforms was undertaken within and across breeds exploiting population-wide linkage disequilibrium. The mean allele concordance rate per breed from LD to HD when undertaken using a single breed or multiple breed reference population varied from 0.956 to 0.974 and from 0.947 to 0.967, respectively. The mean allele concordance rate per breed from 50K to HD when undertaken using a single breed or multiple breed reference population varied from 0.987 to 0.994 and from 0.987 to 0.993, respectively. The accuracy of imputation was generally greater when the reference population was solely comprised of the breed to be imputed compared to when the reference population comprised of multiple breeds, although the impact