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
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
Editor’s Choice – Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging
By developing a comprehensive and quantitative metric for physiological age of Drosophila, Edward Giniger and colleagues show that a neurodegeneration mutant produces its effects in part by accelerating the absolute rate of aging.
First Person interviews
Have you seen our interviews with the early-career first authors of our papers? Recently, we caught up with first authors Sarah Foriel, Henna Myllymäki and Mirja Niskanen, Wenqing Zhou, Rifdat Aoidi and Amy Irving.
Review – Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches
In a new Review article, Jaap M. J. den Toonder and colleagues evaluate the recent contributions of cancer-on-a-chip models to our understanding of the tumor microenvironment and its role in the onset of metastasis. The authors also provide an outlook for future applications of this emerging technology.
DMM Conference Travel Grants
Are you an early career scientist with plans to attend a scientific meeting, conference, workshop or course relating to the areas of research covered by DMM? The next round of applications for DMM Conference Travel Grants closes on 4 May 2018. Find out more here and get your application in soon.
Why should you publish your next paper in DMM?
DMM aims to promote human health by encouraging collaboration between basic and clinical researchers, covering a diverse range of diseases, approaches and models. Our Editors are all active researchers in the field – your peers, colleagues and mentors, who know how much work has gone into every paper. Recently, we have introduced format-free submission, and we accept peer review reports from other journals, making submission as easy as possible for our authors. Send us your next great paper – publish with us and you'll be in good company.