Type 1 diabetes may result from good genes behaving badly

September 19, 2008

New research from Stanford University scientists suggests that type 1 diabetes, an autoimmune disease that develops in children and young adults, may not be due to bad genes but rather to good genes behaving badly.

Because type 1 diabetes typically runs in families, scientists have looked for inborn genetic errors or gene variants passed on from generation to generation. Although this search has failed to find a single type 1 diabetes gene, many candidate type 1 diabetes susceptibility genes have been identified. These susceptibility genes, located in a region known as the major histocompatibility complex (MHC), help the body distinguish its own cells and tissues from those that are foreign.

Studies in identical twins, however, reveal that the situation is more complicated: often one twin develops type 1 diabetes while the other twin remains disease-free. This pattern of good luck/bad luck led researchers at Stanford to examine whether genetically at-risk individuals respond differently to environmental stimuli. In some cases, the immune system will respond in a benign fashion, while in other cases it will begin an inflammatory response that can ultimately lead to diabetes. The critical difference between health and disease might thus reside not in an individual's genetic blueprint but in how those genes are "expressed"--that is, how the translation of genetic information into proteins or RNA is switched on and off.

In a study supported by the National Institute of Allergy and Infectious Diseases, (NIAID) part of the National Institutes of Health, the Stanford team, led by C. Garrison Fathman, M.D., studied differences in gene expression between two groups of mice. The first group, non-obese diabetic mice, spontaneously develop type 1 diabetes. The second group, mice genetically identical to the first group except for their MHC genes, do not develop the disease.

The researchers looked at gene expression in three different tissues in the diabetic and non-diabetic mice at separate times after birth. In the first few weeks of life, they found an explosion of changes in gene expression in the pancreatic lymph nodes, spleen and circulating blood cells of the diabetic mice compared with those in the non-diabetic mice. At 8 weeks, this activity had quieted down. But several weeks later, when the mice were 12 weeks old, a second explosion of changes in gene expression occurred in the diabetic mice in all three tissues examined: pancreatic lymph nodes, spleen and blood cells.

According to Dr. Fathman, the results suggest that type 1 diabetes may not result from genetic mutations but from differences in how normal genes and gene variants are turned on and off during disease progression. In addition to identifying altered genes that may indicate potential avenues for therapeutic or preventive treatments, the authors also found patterns of coordinated gene expression that may prove useful as biomarkers of disease onset or progression.

Citation: K Kodama et al. Tissue- and age-specific changes in gene expression during disease induction and progression in nod mice. Clinical Immunology DOI: 10.1016/j.clim.2008.07.028 (2008).

Source: National Institute of Allergy and Infectious Diseases

Explore further: Circadian genes go to sleep every day at the periphery of the nucleus

Related Stories

MouthLab: Patients' vital signs are just a breath away

August 24, 2015

Engineers and physicians at the Johns Hopkins University School of Medicine have developed a hand-held, battery-powered device that quickly picks up vital signs from a patient's lips and fingertip. Updated versions of the ...

A model for ageing

August 7, 2015

Life is short, especially for the killifish, Nothobranchius furzeri: It lives for only a few months and then its time is up. During that short lifespan it passes through every phase of life from larva to venerable old fish. ...

Expanding theory of evolution

August 5, 2015

An Indiana University professor is part of an international team of biologists working to expand Darwin's theory of evolution to encompass factors that influence a species' growth and development beyond genetics—as well ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.