NDLI: A systematic strategy for large-scale analysis of genotype–phenotype correlations: identification of candidate genes involved in African trypanosomiasis

Content Provider	PubMed Central
Author	Fisher, Paul Cornelia, Hedeler Wolstencroft, Katherine Hulme, Helen Noyes, Harry Kemp, Stephen Stevens, Robert Brass, Andrew
Copyright Year	2007
Abstract	It is increasingly common to combine Microarray and Quantitative Trait Loci data to aid the search for candidate genes responsible for phenotypic variation. Workflows provide a means of systematically processing these large datasets and also represent a framework for the re-use and the explicit declaration of experimental methods. In this article, we highlight the issues facing the manual analysis of microarray and QTL data for the discovery of candidate genes underlying complex phenotypes. We show how automated approaches provide a systematic means to investigate genotype–phenotype correlations. This methodology was applied to a use case of resistance to African trypanosomiasis in the mouse. Pathways represented in the results identified Daxx as one of the candidate genes within the Tir1 QTL region. Subsequent re-sequencing in Daxx identified a deletion of an amino acid, identified in susceptible mouse strains, in the Daxx–p53 protein-binding region. This supports recent experimental evidence that apoptosis could be playing a role in the trypanosomiasis resistance phenotype. Workflows developed in this investigation, including a guide to loading and executing them with example data, are available at http://workflows.mygrid.org.uk/repository/myGrid/PaulFisher/.
Related Links	http://dx.doi.org/10.1093/nar/gkm623
Starting Page	5625
File Format	PDF
ISSN	13624962
e-ISSN	13624962
Journal	Nucleic Acids Research
Issue Number	16
Volume Number	35
Language	English
Publisher	Oxford University Press
Publisher Date	2007-08-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

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