CONICET | Buscador de Institutos y Recursos Humanos

Linking the effects of genetic variations (GVs) to their functional outcomes is a major issue in bioinformatics, especially now that human next-generation sequencing projects generate millions of previously unknown single nucleotide variants. These GVs can be related to many pathological conditions and may influence susceptibility to disease and drug treatment. GVs are compiled in databases (DBs) that offer useful information, but are mostly aimed at investigators, lacking data regarding the effects of GVs in human health. Also, many times these effects are unknown because they get masked by heterozygosity. That?s why over the years, many tools have been developed to predict the effect of variations. Towards the generation of a DB designed for health specialists in the human genetics field, we decided to start compiling all the sequence, experimental and predictive information regarding the GVs of the CYP21A2 gene, which encodes the enzyme 21-hydroxylase. The deficiency in this enzyme accounts for 90?95% of the congenital adrenal hyperplasia cases, and has been throughly studied in our laboratory. The most comprehensive DB regarding the clinical effects of variations in the CYP21A2 gene is CYPallels, which contains 202 GVs, hasn?t been updated since 2010 and mostly accounts for GVs that come from clinical cases. To update and expand this data, we explored different on-line DBs as well as our own data, and found ~750 GVs, with 532 reported after 2010. From the total of GVs, ~350 affects the coding region and ~400 are found in introns and untranslated regions. An effect on human health is reported for only ~240 DVs, classified as benign or as related to a form of adrenal hyperplasia. The tools developed to acquire and clean-up the data for CYP21A2, will be used to build a DB which, in conjunction with state of the art prediction tools, will offer health professionals useful information regarding genetic disorders.