IP: Dr. Jorge Ferrer

Resumen del proyecto: Diabetes mellitus is a group of metabolic disorders. It affects >400 million people worldwide and is expected to increase to 500 million by 2030. It is a major cause of blindness, amputations, and kidney disease. In healthy individuals, increased levels of glucose in the blood signal the beta cells in the pancreatic islets of Langerhans, located in the pancreas, to release insulin into the blood which lowers the blood glucose. Dysregulation of insulin producing beta cells causes a glucose imbalance leading to diabetes pathogenesis. Major forms of diabetes include autoimmune Type 1 diabetes (T1D), where the immune system attacks the pancreatic beta cells and Type 2 diabetes (T2D), which results from insulin resistance coupled with dysfunction of beta cells in individuals who are often obese. T1D and T2D are caused by the interaction of environmental factors with a polygenic background. A smaller group (~0.5-1%) develops Mendelian (or Monogenic) diabetes, which is known to be caused by mutations in ~30 genes. Understanding the genetic cause of all forms of diabetes will enable more efficient, personalized therapies. Over 50% of cases with a clinical diagnosis of Maturity Onset Diabetes of the Young (MODY), the most prevalent form of Mendelian diabetes, do not have an identifiable genetic cause after screening known protein-coding genes, suggesting that causal mutations are non-coding. This suggests that Mendelian diabetes may sometimes result from mutations in non-coding genome sequences, in particular in enhancer sequences that provide long-range regulation of gene transcription in pancreatic islets. Our hypothesis is that an unknown number of individuals develop diabetes due to highly penetrant mutations in tissue-specific regulatory elements. A secondary hypothesis is that enhancer defects might cause diabetic phenotypes that are distinct from previous classifications of human diabetes. We have generated a targeted sequencing design which allows us to screen for regulatory mutations. We have already sequenced ~3000 individuals, the majority of which are from European descent, but we require more controls individuals for a more balanced experiment. This is our reason for applying to the “Banco ADN” , so that we may obtain additional DNA from individuals of European descent that do not have diabetes or other metabolic disease.

Entidad financiadora: European Research Council Executive Agency (ERCEA)