Applications of targeted gene capture and next-generation sequencing technologies in studies of human deafness and other genetic disabilities

• Type of Material: Article
• Authors: Xi Erick Lin, Emory University; Wenxue Tang, Emory University; Shoeb Ahmad, Emory University; Jingqiao Lu, Emory University; Candice C. Colby, Emory University; Jason Zhu, Emory University; Qing Yu, Emory University
• Language: English
• Date: 2012-06
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.heares.2012.01.004
• Title of Journal or Parent Work: Hearing Research
• ISSN: 0378-5955
• Volume: 288
• Issue: 0
• Start Page: 67
• End Page: 76
• Grant/Funding Information: This study was supported by grants to Lin from the National Institute on Deafness and other Communication Disorders (NIDCD 4R33DC010476, 1R41DC009713 and RO1 DC006483).; Tang received grant support from NIDCD (R21 DC008672).; This research project was supported in part by the GRA genome center of the Emory University School of Medicine.
• Keywords: gene enrichment; review; genetics; genes; deafness; mutations; exome; next-generation sequencing
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Genetics

Abstract

The goal of sequencing the entire human genome for $1,000 is almost in sight. However, the total costs including DNA sequencing, data management, and analysis to yield a clear data interpretation are unlikely to be lowered significantly any time soon to make studies on a population scale and daily clinical uses feasible. Alternatively, the targeted enrichment of specific groups of disease and biological pathway-focused genes and the capture of up to an entire human exome (~1% of the genome) allowing an unbiased investigation of the complete protein-coding regions in the genome are now routine. Targeted gene capture followed by sequencing with massively parallel next-generation sequencing (NGS) has the advantages of 1) significant cost saving, 2) higher sequencing accuracy because of deeper achievable coverage, 3) a significantly shorter turnaround time, and 4) a more feasible data set for a bioinformatic analysis outcome that is functionally interpretable. Gene capture combined with NGS has allowed a much greater number of samples to be examined than is currently practical with whole-genome sequencing. Such an approach promises to bring a paradigm shift to biomedical research of Mendelian disorders and their clinical diagnoses, ultimately enabling personalized medicine based on one’s genetic profile. In this review, we describe major methodologies currently used for gene capture and detection of genetic variations by NGS. We will highlight applications of this technology in studies of genetic disorders and discuss issues pertaining to applications of this powerful technology in genetic screening and the discovery of genes implicated in syndromic and non-syndromic hearing loss.