Gene crucial to the development of celiac disease found in ‘junk’ DNA.


Coeliac disease is a chronic, immunological disease that is manifested as intolerance to gluten proteins present in wheat, rye and barley. This intolerance leads to an inflammatory reaction in the small intestine which hampers the absorption of nutrients, with the only treatment available a strict, life-long, gluten-free diet.  It is known that coeliac disease develops in people who have a genetic susceptibility, however, despite the fact that 40% of the population carry the most decisive risk factor, only 1% go on to develop the disease.

Therefore, it has long been a point of conjecture where other genetic risk factors lie, as the aforementioned figure suggests they must exist.  Now, a study from researchers at University of the Basque Country has identified a major risk factor for coeliac disease in the so-called ‘junk’ DNA.  The team state that they have identified a long noncoding RNA (lncRNA), lnc13, that suppresses inflammatory gene expression in macrophages and harbors a celiac disease–associated haplotype block.  The study is published in the journal Science.

Previous studies show ‘junk’ or noncoding DNA makes up at least 95% of human DNA. It is the least-known part because, unlike the remaining 5%, it is not involved in synthesising proteins. Nevertheless, light is gradually being shed on noncoding DNA’s role in the control of the overall functioning of the genome. Recent studies have implicated noncoding DNA in regulating important processes in humans such as immune response.  The current study investigates noncoding DNA for risk factors leading to the autoimmune disease, coeliac disease.

The current study shows that a key gene in the regulation of the inflammatory response observed in coeliac patients can be found in one of the regions of the junk genome, namely 1nc13. Results show that the ribonucleic acid produced by this gene belongs to the family of lncRNA and is responsible for maintaining the normal levels of expression of pro-inflammatory genes.

Data findings show in coeliacs, this lncRNA is hardly produced at all so the levels of these inflammatory genes are not properly regulated and their expression is increased. The group observed that besides being produced in low quantities, the 1nc13 produced by coeliac patients has a variant that alters the way it functions and it is in that way an inflammatory environment is created and the development of the disease encouraged.

The team surmise that their findings confirm 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. For the future, the researchers state they plan to investigate whether the low levels of this RNA are an early feature of coeliac disease, which could be used as a diagnostic tool before its onset.

Source: UPV/EHU-University of the Basque Country

 

This image shows intestinal cells in a healthy individual in which the non-coding RNA of the Inc13 gene appears in red (the red dots would not be seen in a celiac patient).  Credit: A. Castellanos.

This image shows intestinal cells in a healthy individual in which the non-coding RNA of the Inc13 gene appears in red (the red dots would not be seen in a celiac patient). Credit: A. Castellanos.

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