Integrative genetic analysis of transcription modules: towards filling the gap between genetic lociand inherited traits

Journal Article · Sat Jan 01 04:00:00 EST 2005 · Human Molecular Genetics

DOI:https://doi.org/10.1093/hmg/ddi462· OSTI ID:930765

Li, Hongqiang ^[1]; Chen, Hao ^[1]; Bao, Lei ^[1]; Manly, Kenneth ^[1]; Chesler, Elissa J ^[2]; Lu, Lu ^[1]; Wang, Jintao ^[1]; Zhou, Mi ^[1]; Williams, Robert ^[1]; Cui, Yan ^[1]

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1. University of Tennessee Health Science Center, Memphis
2. ORNL

Genetic loci that regulate inherited traits are routinely identified using quantitative trait locus (QTL) mapping methods. However, the genotype-phenotype associations do not provide information on the gene expression program through which the genetic loci regulate the traits. Transcription modules are 'selfconsistent regulatory units' and are closely related to the modular components of gene regulatory network [Ihmels, J., Friedlander, G., Bergmann, S., Sarig, O., Ziv, Y. and Barkai, N. (2002) Revealing modular organization in the yeast transcriptional network. Nat. Genet., 31, 370-377; Segal, E., Shapira, M., Regev, A., Pe'er, D., Botstein, D., Koller, D. and Friedman, N. (2003) Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data. Nat. Genet., 34, 166-176]. We used genome-wide genotype and gene expression data of a genetic reference population that consists of mice of 32 recombinant inbred strains to identify the transcription modules and the genetic loci regulating them. Twenty-nine transcription modules defined by genetic variations were identified. Statistically significant associations between the transcription modules and 18 classical physiological and behavioral traits were found. Genome-wide interval mapping showed that major QTLs regulating the transcription modules are often co-localized with the QTLs regulating the associated classical traits. The association and the possible co-regulation of the classical trait and transcription module indicate that the transcription module may be involved in the gene pathways connecting the QTL and the classical trait. Our results show that a transcription module may associate with multiple seemingly unrelated classical traits and a classical trait may associate with different modules. Literature mining results provided strong independent evidences for the relations among genes of the transcription modules, genes in the regions of the QTLs regulating the transcription modules and the keywords representing the classical traits.

• Research Organization: Oak Ridge National Laboratory (ORNL)
• Sponsoring Organization: ORNL Program Development
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 930765
• Journal Information: Human Molecular Genetics, Journal Name: Human Molecular Genetics Journal Issue: 3 Vol. 15
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
GENETICS
GENOTYPE
MICE
MINING
STRAINS
TRANSCRIPTION
YEASTS