Disruptive mutation detected in the cdcp2 gene by whole genome sequencing in identical twin sisters suffering from Multiple Sclerosis

چکیده مقاله

Background: multiple sclerosis is categorized as an autoimmune disease with unknown etiology. Although population genetic studies suggest the environmental influence as a risk factor for the MS prevalence, Genome wide association study (GWAS) studies in turn postulate the genetic condition for the MS susceptibility. Linkage analysis candidates several HLA and non- HLA genes involved in MS outcome. In recent decade, emergency of new methods for genome sequencing known as NGS opens new area for detection of novel variations in human genome. The NGS analysis of the identical twin sister affected by MS prepares the best opportunity for the variation detection and the comparison between the genetic or environmental involvement in MS susceptibility. Material and Method: Extracted genomic DNA from an identical twin sister with MS was subjected for whole genome sequencing by the Illumina platform. Furthermore, 50 unrelated MS patients and 137 healthy individuals were selected for this study. Result: Analysis of whole genome sequencing revealed the detection of a novel homozygous frame shift mutation (indel) in the fourth exon of the cdcp2 gene has been annotated as c. 1217_1218insG: p. A406fs. This change was Sanger validated in MS affected twin. But, all the healthy individuals tested here as control were negative for the mentioned change. In other hands, from 50 further MS individuals, 38 percent was homozygous and another 56 percent was heterozygous for the novel indel, respectively. Six percent (n=3) of MS affected individuals showed normal allele. Discussion: The cdcp2 gene is with the location number LOC200008, mapped to chromosome 1p32. It is stated that the cdcp2 is predicted to have oxidoreductase activity and is potentially involved in cholesterol biosynthesis and electron transport. We also suppose that this gene might be involved in the MS etiology and suggest functional assay for the cdcp2 gene.

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