By turning the conventional method of hunting for disease genes on its head, a team of geneticists has discovered three new genes linked to obesity; unlike the standard approach, the new method could also provide information not only about which genes are linked to complex diseases but also about the mechanisms by which they exert their effects.
Traditionally, geneticists search for the DNA sequences that underlie complex conditions, such as Alzheimer's or heart disease, by compiling lists of genetic variants and seeing which ones tend to be correlated with increased disease incidence. Unfortunately, explain researchers led by Eric Schadt in Nature, although this approach can tell you which sequences might be implicated, it usually gives little information about a genetic variant's actual effects.
Schadt and colleagues reversed the traditional method by sorting mice into different categories of obesity, and comparing gene expression in the liver and fat tissues of these different animals versus mice of a normal weight. Their method, called a 'molecular network' approach, suggests that three genes - Lpl, Lactb and Ppm1l - seem to be involved in promoting obesity, creating new targets for therapeutic interventions.
In another study in this week's Nature, a team led by Schadt and his colleague Kari Stefansson uses the molecular network approach to hunt for causal factors in human obesity. Using more than 1,000 blood samples and almost 700 samples of fat tissues from Western volunteers, the researchers show that people with a higher body mass index have characteristic patterns of gene activation in their fatty tissues that are not necessarily apparent in the blood.
Eric Schadt (Rosetta Inpharmatics, Seattle, Washington, USA)
Kari Stefansson (deCODE Genetics, Reykjavik, Iceland)
Abstracts available online:
(C) Nature press release.
Message posted by: Trevor M. D'Souza