An integrative genomics strategy for systematic characterization of genetic loci modulating phenotypes

Lei Bao, Jeremy L. Peirce, Mi Zhou, Hongqiang Li, Dan Goldowitz, Robert Williams, Lu Lu, Yan Cui

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Naturally occurring genetic variations may affect certain phenotypes through influencing transcript levels of the genes that are causally related to those phenotypes. Genomic regions harboring common sequence variants that modulate gene expression can be mapped as quantitative trait loci (QTLs) using a newly developed genetical genomics approach. This enables a new strategy for systematically mapping novel genetic loci underlying various phenotypes. In this work, we started from a seed set of genes with variants that are known to affect behavioral and neurological phenotypes (as recorded in Mammalian Phenotype Ontology Database) and used microarrays to analyze their expression levels in brain samples of a panel of BXD recombinant inbred mouse strains. We then systematically mapped the QTLs controlling the expression of these genes. Candidate causal genes in the QTL intervals were evaluated for evidence of functional genetic polymorphisms. Using this method, we were able to predict novel genetic loci and causal genes for a number of behavioral and neurological phenotypes. Lines of independent evidence supporting some of our results were provided by transcription factor binding site analysis and by biomedical literature. This strategy integrates gene-phenotype relations from decades of experimental mutagenesis studies and new genomic resources to provide an approach to rapidly expand knowledge on genetic loci modulating phenotypes.

Original languageEnglish (US)
Pages (from-to)1381-1390
Number of pages10
JournalHuman Molecular Genetics
Volume16
Issue number11
DOIs
StatePublished - Jun 1 2007

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Genetic Loci
Genomics
Phenotype
Quantitative Trait Loci
Genes
Gene Expression
Inbred Strains Mice
Genetic Polymorphisms
Microarray Analysis
Mutagenesis
Seeds
Transcription Factors
Binding Sites
Databases
Brain

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

An integrative genomics strategy for systematic characterization of genetic loci modulating phenotypes. / Bao, Lei; Peirce, Jeremy L.; Zhou, Mi; Li, Hongqiang; Goldowitz, Dan; Williams, Robert; Lu, Lu; Cui, Yan.

In: Human Molecular Genetics, Vol. 16, No. 11, 01.06.2007, p. 1381-1390.

Research output: Contribution to journalArticle

Bao, Lei ; Peirce, Jeremy L. ; Zhou, Mi ; Li, Hongqiang ; Goldowitz, Dan ; Williams, Robert ; Lu, Lu ; Cui, Yan. / An integrative genomics strategy for systematic characterization of genetic loci modulating phenotypes. In: Human Molecular Genetics. 2007 ; Vol. 16, No. 11. pp. 1381-1390.
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