Integrative genetic analysis of transcription modules

Towards filling the gap between genetic loci and inherited traits

Hongqiang Li, Hao Chen, Lei Bao, Kenneth F. Manly, Elissa J. Chesler, Lu Lu, Jintao Wang, Mi Zhou, Robert Williams, Yan Cui

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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 'self-consistent 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.

Original languageEnglish (US)
Pages (from-to)481-492
Number of pages12
JournalHuman Molecular Genetics
Volume15
Issue number3
DOIs
StatePublished - Feb 1 2006

Fingerprint

Genetic Transcription
Genetic Loci
Gene Regulatory Networks
Viverridae
Quantitative Trait Loci
Gene Expression
Genome
Population Genetics
Genetic Association Studies
Regulator Genes
Genes
Yeasts
Genotype

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Integrative genetic analysis of transcription modules : Towards filling the gap between genetic loci and inherited traits. / Li, Hongqiang; Chen, Hao; Bao, Lei; Manly, Kenneth F.; Chesler, Elissa J.; Lu, Lu; Wang, Jintao; Zhou, Mi; Williams, Robert; Cui, Yan.

In: Human Molecular Genetics, Vol. 15, No. 3, 01.02.2006, p. 481-492.

Research output: Contribution to journalArticle

Li, Hongqiang ; Chen, Hao ; Bao, Lei ; Manly, Kenneth F. ; Chesler, Elissa J. ; Lu, Lu ; Wang, Jintao ; Zhou, Mi ; Williams, Robert ; Cui, Yan. / Integrative genetic analysis of transcription modules : Towards filling the gap between genetic loci and inherited traits. In: Human Molecular Genetics. 2006 ; Vol. 15, No. 3. pp. 481-492.
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