Validació d’un estudi d’exòmica en una familia afectada d’esclerosi múltiple

Abstract

Multiple sclerosis (MS) is the leading reason of nontraumatic neurological disability in young adults. We know that genetics plays a role in its development. It has described many susceptibility genes for MS, but together they are not able to explain the development of the disease. This project is based on the genetic study of a gypsy family with a large number of individuals affected by MS and a high level of inbreeding. Therefore, the genetic study of this family has excellent conditions to detect MS susceptibility genes. This project aims to validate genetic changes identified in an exome study realized in a small number of individuals of the total family (4 individuals affected by MS and 1 healthy individual used as control for the reference alleles). On the basis of the results of the exome study, it has been selected for validation in all individuals of the family, those genes in which the function of the resulting protein and the functional consequence of genetic change may be involved in the development of MS. Previously to the genetic study, genes sequences has been searched, the changes localized and identified the regions of interest. Then, the optimal conditions for amplification have been established. Validation of selected changes has been made by Sanger sequencing or RT-PCR with TaqMan® probes. No significant differences were observed for the genotype between healthy and affected individuals in any analyzed gene. Due to the low coverage in some regions analyzed in the exome study, it has observed low concordance between genotyping provided by exome study and the one obtained in the validation. Because of the importance of HLA in MS susceptibility, DRB1 and DQB1 genes have been analyzed by Luminex® system. None of the studied individuals presents the genotypes DRB1*15:01 and DQB1*06: 02 considered at risk of MS. However, the DRB1*03 genotype is common in this family. The genes studied in this project are not able to explain the presence of MS in the family