title: High-Density Genotypes of Inbred Mouse Strains: Improved Power and Precision of Association Mapping.
abstract: Human genome-wide association studies have identified thousands of loci associated with disease phenotypes. Genome-wide association studies also have become feasible using rodent models and these have some important advantages over human studies, including controlled environment, access to tissues for molecular profiling, reproducible genotypes, and a wide array of techniques for experimental validation. Association mapping with common mouse inbred strains generally requires 100 or more strains to achieve sufficient power and mapping resolution; in contrast, sample sizes for human studies typically are one or more orders of magnitude greater than this. To enable well-powered studies in mice, we have generated high-density genotypes for ∼175 inbred strains of mice using the Mouse Diversity Array. These new data increase marker density by 1.9-fold, have reduced missing data rates, and provide more accurate identification of heterozygous regions compared with previous genotype data. We report the discovery of new loci from previously reported association mapping studies using the new genotype data. The data are freely available for download, and Web-based tools provide easy access for association mapping and viewing of the underlying intensity data for individual loci.
authors.affiliation: Departments of Human Genetics, Medicine, Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California 90095-1679.
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Rau
authors.affiliation: Departments of Human Genetics, Medicine, Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California 90095-1679.
authors.forename: Brian
authors.initials: B
authors.lastname: Parks
authors.affiliation: Department of Anesthesiology, UCLA, Los Angeles, California 90095-1679.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Computer Sciences, UCLA, Los Angeles, California 90095-1679.
authors.forename: Eleazar
authors.initials: E
authors.lastname: Eskin
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609.
authors.forename: Petr
authors.initials: P
authors.lastname: Simecek
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Churchill
authors.affiliation: Departments of Human Genetics, Medicine, Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California 90095-1679 jlusis@mednet.ucla.edu.
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D060005:Genotyping Techniques; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
keywords: HMDP; genotyping; mouse; mouse diversity array