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Sick Genes

Researchers uncover gene mutations that contribute to disease by screening the genomes of thousands of healthy and ill people
genetic-testing



© ISTOCKPHOTO.COM/ANDREI TCHERNOV
The human genome contains more than three billion base pairs of adenine (A), thymine (T), guanine (G) and cytosine (C)—some of the principal molecules that make up DNA. Found among those pairings are so-called single nucleotide polymorphisms (SNP), changes or mutations in the order of these molecules. A person of European descent typically has around eight million SNPs, many of which are shared widely throughout the population. By comparing some 500,000 of these common variations, a team of research groups discovered 24 genes and regions of the genome that raise a person's risk of developing diseases ranging from clinical depression to diabetes.

"We are looking for parts of the genome that show differences. One of the letters [A, T, G or C] in the DNA code is more common in people with the disease and the other variant is more common in healthy people," says statistician Peter Donnelly of the University of Oxford and chair of the Wellcome Trust Case Control Consortium, which brought together more than 50 British scientific groups to analyze the genomes of 17,000 individuals. "The genes that are involved aren't necessarily what we would have expected."

The researchers compared the genomes of approximately 2,000 people suffering from one of seven diseases—bipolar disorder, coronary heart disease, Crohn's disease, high blood pressure, rheumatoid arthritis and both types of diabetes—with those of a control group of 3,000 healthy individuals. Mutations most frequently found in one or the other of the contrasted groups enhance or reduce the risk of developing that disease, Donnelly says.

For example, researchers probing type 1 diabetes report in Nature and Nature Genetics that they found seven new genes and regions associated with an elevated risk of developing the disease. Among them: an unexpected gene shared with sufferers of Crohn's disease, an inflammatory bowel illness believed to be caused by an immune reaction to normal gut bacteria. "No one had really ever expected that there was a link," says geneticist John Todd of the University of Cambridge.

Identifying such genetic risk factors could lead to new treatments and, perhaps, ways to prevent activating a disorder in the genetically predisposed. "Individuals might be able to learn which disease they are more at risk of and be in a position to make more informed decisions about lifestyle," Donnelly says, although the researchers caution that such screening is probably still at least several years down the road.

That is because genes, although potent predictors, are not always the sole cause of particular diseases. For instance, environmental factors, lifestyle (diet, exercise, etcetera) and exposure to infections can all play roles in determining whether an individual will develop heart disease, for example. "It's about hundreds of genes in your genome contributing a threshold of genetic susceptibility," Todd says. "It's not about one gene."

Nevertheless, on average, having one copy of some of the newly identified genes raises a person's chances of developing one of the seven studied diseases by 20 to 40 percent, and those with two copies face nearly double that risk, researchers say. "What hasn't been clear is exactly which bits of the genome have an effect and which variants make people more [or less] likely to get a disease," Donnelly notes. "By turning the lights on half a million parts of the genome, you get to see a large part of the variation that is there."

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