Next generation sequencing – towards translation into clinical practice

Abstract

Despite substantial eff orts, the cause of a signifi cant proportion of mendelian disorders is still unknown. Recently, signifi cant advances in determination of nucleotide sequence present an opportunity to investigate the genetic material down to a single nucleotide resolution on the whole exome or genome scale. This opens complete possibilities for deciphering genetic etiology of genetic disorders and, most importantly, expanding the fi eld of genetic studies from limited cases of diseases occurring in large families to smaller familial confi gurations, making detection of causative genes possible even in trios of parents with a single aff ected proband. Despite the development in both the technology of next generation sequencing and increases in computational power for complex data analysis, the interpretation of results, making sense of genome-scale information in medical setting and conveying this information to the patient, have been lagging behind. In addition, novel ethical questions have opened, especially those related to reporting of incidental fi ndings. These issues are the key points for discussion prior to setting the protocols and guidelines for implementing the whole exome and genome sequencing into clinical practice. This overview will initially give a brief introduction to the technical background behind the next generation sequencing and methodological steps involved. Basic introduction to some of the key steps in data analysis of the next generation sequencing data and challenges encountered thereby will also be given, based on our experiences at the Centre for Mendelian Genomics in Slovenia.