Building single nucleotide polymorphism-derived gene regulatory networks: towards functional genome-wide association studies

Reverter, A. and Fortes, M. R. S. (2013) Building single nucleotide polymorphism-derived gene regulatory networks: towards functional genome-wide association studies. Journal of Animal Science, 91 2: 530-536. doi:10.2527/jas.2012-5780


Author Reverter, A.
Fortes, M. R. S.
Title Building single nucleotide polymorphism-derived gene regulatory networks: towards functional genome-wide association studies
Journal name Journal of Animal Science   Check publisher's open access policy
ISSN 0021-8812
1525-3163
Publication date 2013-02
Year available 2012
Sub-type Article (original research)
DOI 10.2527/jas.2012-5780
Volume 91
Issue 2
Start page 530
End page 536
Total pages 7
Place of publication Savoy, IL, United States
Publisher American Society of Animal Science
Collection year 2013
Language eng
Abstract The advent of economically viable high-throughput genetic and genomic techniques has equipped animal geneticists with an unprecedented ability to generate massive amounts of molecular data. As a result, large lists of genes differentially expressed in many experimental conditions of interests have been reported and, likewise, the association of an ever growing number of DNA variants with phenotypes of importance is now a routine endeavor. Whereas these studies have greatly improved our understanding of the genetic basis of complex phenotypes, they have also revealed the difficulty in explaining more than a fraction of the genetic variance. Inspired by this data-rich and knowledge-poor dichotomy, systems biology aims at the formal integration of seemingly disparate datasets allowing for a holistic view where key properties of the systems emerge as an intuitive feature and enabling the generation of testable hypothesis. Herein, we present two examples of integrating molecular data anchored in the power of gene network inference. The first example is concerned with the onset of puberty in Bos indicus-influenced cows bred in Australia. Using the results from genome-wide association studies across a range of phenotypes, we developed what we termed an association weight matrix to generate a gene network underlying phenotypes of puberty in cattle. The network was mined for the minimal set of transcription factor genes whose predicted target spanned the majority of the topology of the entire network. The second example deals with piebald, a pigmentation phenotype in Merino sheep. Two networks were developed: a regulatory network and an epistatic one. The former is inferred based on promoter sequence analysis of differentially expressed genes. The epistatic network is built from two-locus models among all pair wise associated polymorphisms. At the intersection between these two networks, we revealed a set of genes and gene-gene interactions of validated and de novo predicted relevance to the piebald phenotype. We argue that these new approaches are holistic and therefore more appropriate than traditional approaches for investigating genetic mechanisms underlying complex phenotypes of importance in livestock species.
Keyword Epistasis
Gene network
Genome-wide association
Transcription Factor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 24 October 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Alliance for Agriculture and Food Innovation
Official 2013 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 07 Feb 2013, 10:31:00 EST by Marina Fortes on behalf of School of Veterinary Science