Human Molecular Genetics Advance Access published online on December 21, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi462
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Molecular Sciences, University of Tennessee Health Science Center; Center of Genomics and Bioinformatics, University of Tennessee Health Science Center
* To whom correspondence should be addressed. 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 (1,2). 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 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 coregulation 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 key words representing the classical traits.
Received June 9, 2005
Revised September 1, 2005
Accepted November 2, 2005
Article
Integrative genetic analysis of transcription modules: towards filling the gap between genetic loci and inherited traits
Hongqiang Li 1,
Hao Chen 2,
Lei Bao 1,
Kenneth F. Manly 3,
Elissa J. Chesler 4,
Lu Lu 5,
Jintao Wang 6,
Mi Zhou 1,
Robert W. Williams 7,
and
Yan Cui 8 *
2 Department of Pharmacology, University of Tennessee Health Science Center
3 Center of Genomics and Bioinformatics, University of Tennessee Health Science Center; Department of Anatomy and Neurobiology, University of Tennessee Health Science Center; Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center
4 Department of Anatomy and Neurobiology, University of Tennessee Health Science Center
5 Center of Genomics and Bioinformatics, University of Tennessee Health Science Center; Department of Anatomy and Neurobiology, University of Tennessee Health Science Center
6 Center of Genomics and Bioinformatics, University of Tennessee Health Science Center
7 Center of Genomics and Bioinformatics, University of Tennessee Health Science Center; Department of Anatomy and Neurobiology, University of Tennessee Health Science Center; Department of Pediatrics, University of Tennessee Health Science Center
8 Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Ave, Memphis, TN 38163, USA; Center of Genomics and Bioinformatics, University of Tennessee Health Science Center
Yan Cui, E-mail: ycui2{at}utmem.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Pan Network-based multiple locus linkage analysis of expression traits Bioinformatics, June 1, 2009; 25(11): 1390 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Chaibub Neto, C. T. Ferrara, A. D. Attie, and B. S. Yandell Inferring Causal Phenotype Networks From Segregating Populations Genetics, June 1, 2008; 179(2): 1089 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Schliekelman Statistical Power of Expression Quantitative Trait Loci for Mapping of Complex Trait Loci in Natural Populations Genetics, April 1, 2008; 178(4): 2201 - 2216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B.H. Williams, E. K.F. Chan, M. J. Cowley, and P. F.R. Little The influence of genetic variation on gene expression Genome Res., December 1, 2007; 17(12): 1707 - 1716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gao and X. Wang TAPPA: topological analysis of pathway phenotype association Bioinformatics, November 15, 2007; 23(22): 3100 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. X. Jin, H. O'Geen, S. Iyengar, R. Green, and P. J. Farnham Identification of an OCT4 and SRY regulatory module using integrated computational and experimental genomics approaches Genome Res., June 1, 2007; 17(6): 807 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bao, J. L. Peirce, M. Zhou, H. Li, D. Goldowitz, R. W. Williams, L. Lu, and Y. Cui An integrative genomics strategy for systematic characterization of genetic loci modulating phenotypes Hum. Mol. Genet., June 1, 2007; 16(11): 1381 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Schadt and P. Y. Lum Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Reverse engineering gene networks to identify key drivers of complex disease phenotypes J. Lipid Res., December 1, 2006; 47(12): 2601 - 2613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Elnitski, V. X. Jin, P. J. Farnham, and S. J.M. Jones Locating mammalian transcription factor binding sites: A survey of computational and experimental techniques Genome Res., December 1, 2006; 16(12): 1455 - 1464. [Abstract] [Full Text] [PDF]
|
|