Non-coding DNA may affect type 2 diabetes risk

Date: Jan-14-2014Once thought of as "junk" DNA because it does not contain genes that encode

proteins, scientists are starting to discover non-coding DNA can nevertheless influence the

effect of coding DNA, such as switching genes on and off.

Now, a new study led by Imperial College London in the UK suggests variations in these non-coding sections of the genome may play a key role in people's risk for type 2 diabetes.

The study, one of the first to implicate non-coding DNA in disease risk, is published in a

recent online issue of Nature Genetics.

Only about 2% of the human genome is made up of coding DNA - most of the rest remains a

mystery.

Non-coding DNA - the 'dark matter' of the genome

One of the study's Wellcome Trust Senior Investigators, Jorge Ferrer, a professor in

Imperial College's Department of Medicine, says:

"Non-coding DNA, or junk DNA as it is sometimes known, is the dark matter of the genome.

We're only just beginning to unravel what it does."

Type 2 diabetes affects over 300 million people worldwide, including 8% of Americans. The disease

can develop into more serious conditions, such as cardiovascular disease, loss of limbs,

blindness and kidney failure.

In people with type 2 diabetes, the tissues become less responsive to insulin, resulting in

high levels of blood sugar. When this happens in people who do not have type 2 diabetes, the

body compensates by producing more insulin, a hormone that regulates blood sugar.

But in people with type 2 diabetes, the pancreas cannot cope with the increase in demand for

insulin.

Genes are known to play an important role in a person's risk for developing type 2 diabetes,

as are other factors, such as body weight, diet and age.

While many studies have shown there are regions of the non-coding genome where variations

are linked to diabetes risk, it is not very clear what they do.

Sequences regulate gene expression in insulin-producing cells

In this latest study, the researchers identified sequences of non-coding DNA that regulate

gene activity in the insulin-producing cells of the pancreas.

They found these sequences are located in clusters and that variants known to be linked to

risk for type 2 diabetes are also found in these clusters.

Prof. Ferrer says:

"Many people have small DNA variants in such regulatory elements, and these variants affect

gene expression in the cells that produce insulin."

Mark McCarthy, another Wellcome Trust senior investigator and professor at

Oxford University, explains however, that in people with type 2 diabetes, the insulin-producing

cells appear to follow a different pattern of gene expression, adding:

"This study provides some important clues to the mechanisms which are disturbed in the

earliest stages of the development of type 2 diabetes, and may point the way to novel ways of

treating and preventing the disease."

In January 2013, a group of US researchers reported discovering two new non-coding DNA mutations in

melanoma. They said these mutations, which occur in 71% of malignant melanomas, may be even

more common in this deadliest form of skin cancer than the already well-known protein-coding

BRAF gene.

Written by Catharine Paddock PhD

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