Original Research ARTICLE

Front. Genet., 11 January 2013 | http://dx.doi.org/10.3389/fgene.2012.00307

Inferring quantitative trait pathways associated with bull fertility from a genome-wide association study

  • 1Department of Animal Sciences, University of Wisconsin, Madison, WI, USA
  • 2Department of Dairy Science, University of Wisconsin, Madison, WI, USA
  • 3Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA

Whole-genome association studies typically focus on genetic markers with the strongest evidence of association. However, single markers often explain only a small component of the genetic variance and hence offer a limited understanding of the trait under study. As such, the objective of this study was to perform a pathway-based association analysis in Holstein dairy cattle in order to identify relevant pathways involved in bull fertility. The results of a single-marker association analysis, using 1,755 bulls with sire conception rate data and genotypes for 38,650 single nucleotide polymorphisms (SNPs), were used in this study. A total of 16,819 annotated genes, including 2,767 significantly associated with bull fertility, were used to interrogate a total of 662 Gene Ontology (GO) terms and 248 InterPro (IP) entries using a test of proportions based on the cumulative hypergeometric distribution. After multiple-testing correction, 20 GO categories and one IP entry showed significant overrepresentation of genes statistically associated with bull fertility. Several of these functional categories such as small GTPases mediated signal transduction, neurogenesis, calcium ion binding, and cytoskeleton are known to be involved in biological processes closely related to male fertility. These results could provide insight into the genetic architecture of this complex trait in dairy cattle. In addition, this study shows that quantitative trait pathways inferred from single-marker analyses could enhance our interpretations of the results of genome-wide association studies.

Keywords: gene ontology, gene-set analysis, genome-wide study, male fertility, quantitative trait pathway

Citation: Peñagaricano F, Weigel KA, Rosa GJM and Khatib H (2013) Inferring quantitative trait pathways associated with bull fertility from a genome-wide association study. Front. Gene. 3:307. doi: 10.3389/fgene.2012.00307

Received: 04 October 2012; Accepted: 11 December 2012;
Published online: 11 January 2013.

Edited by:

Peter Dovc, University of Ljubljana, Slovenia

Reviewed by:

Ino Curik, University of Zagreb, Croatia
Anna Tomas Sangenis, Fundacio Investigacio Sanitaria Illes Balears, Spain

Copyright: © 2013 Peñagaricano, Weigel, Rosa and Khatib. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Francisco Peñagaricano, Guilherme J. M. Rosa and Hasan Khatib, Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI 53706, USA. e-mail: fpenagarican@wisc.edu; grosa@wisc.edu; hkhatib@wisc.edu