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 – Lifespan analysis of phenotypes in three mouse models of Down syndrome
A comparison of three mouse models of Down syndrome by Diana W. Bianchi and co-workers reveals widespread and unexpected fundamental differences in behavioural, gene expression and brain development phenotypes.
Find out more about the story behind this Editor's Choice article in an interview with first author Nadine M. Aziz.
Review – Hidden features: exploring the non-canonical functions of metabolic enzymes
A new Review from Peiwei Huangyang and M. Celeste Simon, part of our upcoming special issue on Cancer metabolism, summarizes recent findings about multifaceted metabolic enzymes with non-canonical activities outside their core biochemical functions, and how they may provide new therapeutic strategies for cancers.
Featured article – Intramyocardial angiogenetic stem cells and epicardial erythropoietin save the acute ischemic heart
Gustav Steinhoff and colleagues report that cardiac mesenchymal stem cells respond early to myocardial infarction, and that their regenerative capacity is directly upregulated by optimized stimulation of the heart through epicardial erythropoietin delivery.
First Person interviews
Have you seen our interviews with the early-career first authors of our papers? Recently, we caught up with first authors Nadine Aziz, Tingting Sui, Brian Lu, Hannah Gordon, Theresa Kisko, Francisco Javier García-Rodríguez and Laura Schultz.
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.
preLights – Using zebrafish to model the effects of candidate disease gene variants in complex human genetic disorders
Highlighted by Hannah Brunsdon, a recent preprint from Lisa Maves and co-workers describes the first example of modelling a complex genetic disorder in zebrafish, and demonstrates that a human candidate disease variant of unknown significance acts as a modifier gene for congenital heart defects.