High-Resolution Mapping of Gene Expression Using Association in an Outbred Mouse Stock
| Autor: | Eleazar Eskin, Aldons J. Lusis, Alec J. Brozell, Anatole Ghazalpour, Ping-Zi Wen, Charles R. Farber, Desmond J. Smith, Sudheer Doss, Hyun Min Kang, Thomas A. Drake, Ruth Castellanos |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Genetics and Genomics/Animal Genetics Genotype lcsh:QH426-470 Quantitative Trait Loci Population Gene Expression Biology Quantitative trait locus Linkage Disequilibrium Mice 03 medical and health sciences 0302 clinical medicine Inbred strain Family-based QTL mapping Gene mapping Animals Outbred Strains Genetics Animals Genetics and Genomics/Genomics Association mapping education Molecular Biology Genetics (clinical) Ecology Evolution Behavior and Systematics 030304 developmental biology Genetic association 0303 health sciences education.field_of_study Gene Expression Profiling Chromosome Mapping Genetics and Genomics Genetics and Genomics/Gene Expression Chromosomes Mammalian Genetics and Genomics/Genome Projects lcsh:Genetics Liver Expression quantitative trait loci Female 030217 neurology & neurosurgery Research Article |
| Zdroj: | Ghazalpour, A; Doss, S; Kang, H; Farber, C; Wen, PZ; Brozell, A; et al.(2008). High-resolution mapping of gene expression using association in an outbred mouse stock. PLoS Genetics, 4(8). doi: 10.1371/journal.pgen.1000149. UCLA: Retrieved from: http://www.escholarship.org/uc/item/9w62w881 PLoS Genetics, Vol 4, Iss 8, p e1000149 (2008) PLoS Genetics |
| ISSN: | 1553-7404 |
| Popis: | Quantitative trait locus (QTL) analysis is a powerful tool for mapping genes for complex traits in mice, but its utility is limited by poor resolution. A promising mapping approach is association analysis in outbred stocks or different inbred strains. As a proof of concept for the association approach, we applied whole-genome association analysis to hepatic gene expression traits in an outbred mouse population, the MF1 stock, and replicated expression QTL (eQTL) identified in previous studies of F2 intercross mice. We found that the mapping resolution of these eQTL was significantly greater in the outbred population. Through an example, we also showed how this precise mapping can be used to resolve previously identified loci (in intercross studies), which affect many different transcript levels (known as eQTL “hotspots”), into distinct regions. Our results also highlight the importance of correcting for population structure in whole-genome association studies in the outbred stock. Author Summary In rodents, as in humans, traits such as obesity or diabetes are under the influence of many genes spread throughout the genome. Using linkage analysis, the locations of the major contributing genes can be mapped only to very large regions of chromosomes, usually encompassing hundreds of genes. This has made it difficult to identify the underlying genes and mutations. Another approach, analogous to genome-wide association in human populations, is to use association analyses among outbred stocks of mice. In this proof-of-principle article, we make use of common variations that locally perturb gene expression to demonstrate the greatly improved mapping resolution of association in mice. Our results indicate that association analyses in mice are a powerful approach to the dissection of complex traits and their underlying molecular networks. |
| Databáze: | OpenAIRE |
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