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Large-scale in silico mapping of complex quantitative traits in inbred mice. PLoS One 2007 Jul 25;2(7):e651 PMID: 17653278 PMCID: PMC1920557

Pubmed ID

17653278

Abstract

Understanding the genetic basis of common disease and disease-related quantitative traits will aid in the development of diagnostics and therapeutics. The processs of gene discovery can be sped up by rapid and effective integration of well-defined mouse genome and phenome data resources. We describe here an in silico gene-discovery strategy through genome-wide association (GWA) scans in inbred mice with a wide range of genetic variation. We identified 937 quantitative trait loci (QTLs) from a survey of 173 mouse phenotypes, which include models of human disease (atherosclerosis, cardiovascular disease, cancer and obesity) as well as behavioral, hematological, immunological, metabolic, and neurological traits. 67% of QTLs were refined into genomic regions <0.5 Mb with approximately 40-fold increase in mapping precision as compared with classical linkage analysis. This makes for more efficient identification of the genes that underlie disease. We have identified two QTL genes, Adam12 and Cdh2, as causal genetic variants for atherogenic diet-induced obesity. Our findings demonstrate that GWA analysis in mice has the potential to resolve multiple tightly linked QTLs and achieve single-gene resolution. These high-resolution QTL data can serve as a primary resource for positional cloning and gene identification in the research community.

Author List

Liu P, Vikis H, Lu Y, Wang D, You M

Authors

Pengyuan Liu PhD Adjunct Associate Professor in the Physiology department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-38549083432   31 Citations

MESH terms used to index this publication - Major topics in bold

ADAM Proteins
ADAM12 Protein
Animals
Atherosclerosis
Cardiovascular Diseases
Chromosome Mapping
Disease Models, Animal
Genetic Association Studies
Genetic Linkage
Genetic Variation
Genome-Wide Association Study
Humans
Membrane Proteins
Mice
Mice, Inbred Strains
Models, Genetic
Neoplasms
Obesity
Phenotype
Quantitative Trait Loci
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e