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Commentary
Mouse models and the interpretation of human GWAS in type 2 diabetes and obesity
Roger D. Cox, Christopher D. Church
Disease Models & Mechanisms 2011 : dmm.000414 doi: 10.1242/dmm.000414 Published 14 February 2011
Roger D. Cox
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Christopher D. Church
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Abstract

Within the last 3 years, genome-wide association studies (GWAS) have had unprecedented success in identifying loci that are involved in common diseases. For example, more than 35 susceptibility loci have been identified for type 2 diabetes and 32 for obesity thus far. However, the causal gene and variant at a specific linkage disequilibrium block is often unclear. Using a combination of different mouse alleles, we can greatly facilitate the understanding of which candidate gene at a particular disease locus is associated with the disease in humans, and also provide functional analysis of variants through an allelic series, including analysis of hypomorph and hypermorph point mutations, and knockout and overexpression alleles. The phenotyping of these alleles for specific traits of interest, in combination with the functional analysis of the genetic variants, may reveal the molecular and cellular mechanism of action of these disease variants, and ultimately lead to the identification of novel therapeutic strategies for common human diseases. In this Commentary, we discuss the progress of GWAS in identifying common disease loci for metabolic disease, and the use of the mouse as a model to confirm candidate genes and provide mechanistic insights.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms

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Mouse models and the interpretation of human GWAS in type 2 diabetes and obesity
Roger D. Cox, Christopher D. Church
Disease Models & Mechanisms 2011 : dmm.000414 doi: 10.1242/dmm.000414 Published 14 February 2011
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Mouse models and the interpretation of human GWAS in type 2 diabetes and obesity
Roger D. Cox, Christopher D. Church
Disease Models & Mechanisms 2011 : dmm.000414 doi: 10.1242/dmm.000414 Published 14 February 2011

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