Background: Pathogenesis of Multiple Sclerosis (MS) is poorly understood, available evidence suggests that both genetic and environmental components may play some roles.
Objectives: To study the genetic predisposition in familial MS in Saudi population.
Material and Methods: Whole Exome Sequencing (WES) was performed in multigeneration family members. Lifescope software was used for analysis which includes filtering low quality reads, alignment against reference genome (Hg19) and variant call. Variants filtration was performed by in-house developed strategy between the subjects. SNPs and Indels were filtered to look for pathogenic mutations using public databases. In family, we filtered unique variants in the probands and unique shared sequence variants present in carrier parent and proband grandparent. Variants were confirmed by Sanger sequencing using specific designed primers.
Result: The exome sequence resulted in identification of 10,257 variants among 11 unaffected and seven affected family members of our familial MS based on the human reference genome (hg19), of which 1268 variants were found uniquely novels 35 variants were shared between affected members and predicted to have a deleterious or damaging effect. Mutation were confirmed by Sanger sequencing
Conclusion: We predicted involvement of 10 newly candidate genes from 35 new variants in Familial MS. Further studies are required on large cohort scale of familial and sporadic MS.
© 2015 Published by Elsevier Inc.