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PMID: 16934000 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Integrating genetic and network analysis to characterize genes related to mouse weight.

PLoS genetics ·Vol. 2 ·No. 8 ·2006-08-18 ·Pages e130

Ghazalpour A, Doss S, Zhang B, Wang S, Plaisier C, Castellanos R, Brozell A, Schadt EE, Drake TA, Lusis AJ, Horvath S

Abstract

Systems biology approaches that are based on the genetics of gene expression have been fruitful in identifying genetic regulatory loci related to complex traits. We use microarray and genetic marker data from an F2 mouse intercross to examine the large-scale organization of the gene co-expression network in liver, and annotate several gene modules in terms of 22 physiological traits. We identify chromosomal loci (referred to as module quantitative trait loci, mQTL) that perturb the modules and describe a novel approach that integrates network properties with genetic marker information to model gene/trait relationships. Specifically, using the mQTL and the intramodular connectivity of a body weight-related module, we describe which factors determine the relationship between gene expression profiles and weight. Our approach results in the identification of genetic targets that influence gene modules (pathways) that are related to the clinical phenotypes of interest.

MeSH Terms
Animals Body Weight/genetics Chromosome Mapping/methods Cluster Analysis Crosses, Genetic Female Gene Expression Profiling/methods Liver/metabolism Mice Mice, Inbred C3H Mice, Inbred C57BL Models, Genetic Oligonucleotide Array Sequence Analysis/methods Polymorphism, Single Nucleotide Quantitative Trait Loci
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Ghazalpour Anatole
Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.
Doss Sudheer
Zhang Bin
Wang Susanna
Plaisier Christopher
Castellanos Ruth
Brozell Alec
Schadt Eric E
Drake Thomas A
Lusis Aldons J
Horvath Steve
Conflict of Interest

Competing interests. The Molecular Biology Institute is a wholly-owned subsidiary of Merck & Co., Inc.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.0020130
Published
2006-08-18
Epub
2006-00-05
Pages
e130
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC1550283
Subset
IM
Grants
NIGMS NIH HHS · GM08234 · United States
NIGMS NIH HHS · GM07104 · United States
NHLBI NIH HHS · HL28481 · United States
NHGRI NIH HHS · T32 HG002536 · United States
NHLBI NIH HHS · P01 HL028481 · United States
NIGMS NIH HHS · T32 GM007104 · United States
NIAID NIH HHS · U19 AI063603 · United States
NHLBI NIH HHS · HL30568 · United States
NHLBI NIH HHS · P01 HL030568 · United States
NIAID NIH HHS · 1U19AI063603-01 · United States
Databases
GEO
GSE2814
External Links
PubMed source DOI: 10.1371/journal.pgen.0020130 PMC Full Text View journal details
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