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Finding the missing 'LiNCs' in celiac disease

PhD ceremony:Ms B. (Barbara) Hrdlicková
When:May 11, 2015
Supervisor:prof. dr. C. (Cisca) Wijmenga
Co-supervisors:dr. S. (Sebo) Withoff, dr. V.K. Magadi Gopalaiah
Where:Academy building RUG
Faculty:Medical Sciences / UMCG
Finding the missing 'LiNCs' in celiac disease

Celiac disease is a common autoimmune disorder affecting at least 1-3% of the Western population. It belongs to the same group of complex disorders as rheumatoid arthritis and multiple sclerosis characterized by multiple genetic and environmental factors which play a role in the disease development. Celiac disease is the result of an inflammatory response in the small intestine. This is triggered by dietary gluten in grain (wheat, barley, rye), proteins which are abundantly present in the Western diet. The inflammatory damage leads to malnutrition and a wide variety of symptoms such as abdominal pain, chronic diarrhea and anemia. So far, the only effective treatment for celiac disease is a life-long gluten-free diet.

The aim of my thesis project was to identify novel genetic factors predisposing to celiac disease and to investigate how they might contribute to the disease mechanism. My thesis describes novel genetic variants that were identified by looking at the more extreme phenotypes and/or by following-up suggestively associated GWAS variants by increasing the sample size. The results indicate that long non-coding RNAs (lncRNAs), which are a new class of RNA molecules, might be important players in the pathophysiology of celiac disease. The prediction methods I applied in this work can also be used to prioritize interesting cell types for functional studies with these long non-coding RNAs.