Developing Genome and Exome Sequencing for Candidate Gene Identification in Inherited Disorders: An Integrated Technical and Bioinformatics Approach

Abstract

Context.—Advances in sequencing technology with the commercialization of next-generation sequencing (NGS) has substantially increased the feasibility of sequencing human genomes and exomes. Next-generation sequencing has been successfully applied to the discovery of disease-causing genes in rare, inherited disorders. By necessity, the advent of NGS has fostered the concurrent development of bioinformatics approaches to expeditiously analyze the large data sets generated. Next-generation sequencing has been used for important discoveries in the research setting and is now being implemented into the clinical diagnostic arena. Objective.—To review the current literature on technical and bioinformatics approaches for exome and genome sequencing and highlight examples of successful disease gene discovery in inherited disorders. To discuss the challenges for implementing NGS in the clinical research and diagnostic arenas. Data Sources.—Literature review and authors' experience. Conclusions.—Next-generation sequencing approaches are powerful and require an investment in infrastructure and personnel expertise for effective use; however, the potential for improvement of patient care through faster and more accurate molecular diagnoses is high.