Application of whole exome sequencing technique on 1000 Patients affected with Different Genetic Diseases in Isfahan, Iran

Purpose: Whole exome sequencing (WES) that was primarily developed for the research project application, has increasingly been used as a diagnostic tool in clinical medicine. Clearly in the next few years, WES will become accepted as a routine technology in the clinical genetics laboratory for disease diagnosis, prognosis and even treatment. In this paper we report results obtained from 1000 WES analysis. Methods: We performed WES for about 1000 affected patients referred to medical genetic center of Genome during 8-year period (2011– 2019) with a mean coverage of above 100X. Data from WES were analyzed for identification of single nucleotide variants (SNV) or copy number variants (CNV). Results: The most frequently genetic variants were identified in autosomal recessive causing genes (about 57.8%), much higher than autosomal dominant causing genes (7%) and X-linked (3.4%). Although, the majority of the disease causing variants located in nuclear genome, analyzing of mitochondrial genome variants in the WES data yielded six variants in MT-ATP6, MT-ND6, MT-ND5 and MT-TK genes. Interestingly 13 patients had copy number variants (CNV) more than 5 kb. Our analysis results show that less than 30% of the patients failed to obtained acceptable genetic diagnosis by WES-based technology. Diagnostic rate was dependent on the family history information and clinical findings of the affected individuals. Conclusion: Cost effectiveness of this high throughput sequencing has made it more feasible for clinical application. However, Interpretation of unknown significant variants, incidental findings, and novel variants needs more functional, computational evidences.

کلیدواژه ها:

whole exome sequencing ، patients ، rare disease