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Celiac disease: ‘Junk’ DNA not quite junk

celiac disease

Despite the fad to go ‘gluten free,’ the only people who actually suffer from consumption of gluten are those with coeliac disease — so if you don’t have the disease and like to limit yourself to gluten-free foods, you are missing out, and no gluten intolerance is not a real thing. The problem comes from the immune system and is manifested as intolerance to gluten — tasty proteins present in wheat, rye, and barley that help give baked goods their fluff. The intolerance leads to an inflammatory reaction in the small intestine that hampers the absorption of nutrients.

We know that coeliac disease develops in people who have a genetic susceptibility. The problem is that 40% of the population carry the most decisive risk factor (the HLA-DQ2 and DQ8 polymorphisms), only 1% go on to develop the disease.

“What we have here is a complex genetic disease in which many polymorphisms play a role, each making a very small contribution to its development,” explained Ainara Castellanos, lead researcher.

This is where ‘junk DNA’ is thought to come into play. DNA is important because it contains the control manual for the body, every cell in your body has a copy and is duplicated — almost — flawlessly on a regular basis when cells divide. Unfortunately, the instruction manual doesn’t tell us much, only about 5% of our DNA actually codes for synthesizing proteins that the body needs to survive, so we have roughly 95% of what makes you, well… you, labeled as junk.

Fear not, this 95% of DNA probably still has some other underlying function and light is gradually being shed on its role in the control of the overall functioning of the genome. In other words, this junk DNA regulates important processes in the body, you know little things, like immune response, making it a prime candidate for finding the causes of auto-immune diseases such as coeliac disease.

Here is where it gets interesting, a key gene called 1nc13 in the regulating of the inflammatory response observed in coeliac patients has been found in one of the regions of the junk genome. The 1nc13 gene produces a type of ribonucleic acid that belongs to the family of long, non-coding RNAs or lncRNA (which is why it is labeled junk) and is responsible for maintaining the normal levels of expression of pro-inflammatory genes.

The take away for the moment is that just because a gene is labeled junk because it doesn’t actually produce proteins hardly means it does nothing.

In coeliacs, this non-coding RNA is hardly produced at all. The levels of these inflammatory genes, therefore, are not properly regulated and their expression is increased. But besides being produced in low quantities, the 1nc13 produced by coeliac patients has a variant that alters the way it functions.

“That way an inflammatory environment is created and the development of the disease is encouraged,” said Ainara Castellanos.

“This study confirms the importance of the regions of the genome previously regarded as ‘junk’ in the development of common complaints such as coeliac disease and opens up the door to a new possibility for diagnosis.”

“Right now, we are interested in finding out whether the low levels of this RNA are an early feature of coeliac disease (and of other immune diseases), which could be used as a diagnostic tool before its onset,” explained UPV/EHU’s lecturer in Genetics José Ramón Bilbao.

Sources:
Castellanos-Rubio, A., Fernandez-Jimenez, N., Kratchmarov, R., Luo, X., Bhagat, G., Green, P., Schneider, R., Kiledjian, M., Bilbao, J., & Ghosh, S. (2016). A long noncoding RNA associated with susceptibility to celiac disease Science, 352 (6281), 91-95 DOI: 10.1126/science.aad0467

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