New strategies and emerging technologies for massively parallel sequencing: applications in medical research

Elaine R Mardis

doi:10.1186/gm40

Abstract

A variety of techniques that specifically target human gene sequences for differential capture from a genomic sample, coupled with next-generation, massively parallel DNA sequencing instruments, is rapidly supplanting the combination of polymerase chain reaction and capillary sequencing to discover coding variants in medically relevant samples. These studies are most appropriate for the sample numbers necessary to identify both common and rare single nucleotide variants, as well as small insertion or deletion events, which may cause complex inherited diseases. The same massively parallel sequencers are simultaneously being used for whole-genome resequencing and comprehensive, genome-wide variant discovery in studies of somatic diseases such as cancer. Viral and microbial researchers are using next-generation sequences to identify unknown etiologic agents in human diseases, to study the viral and microbial species that occupy surfaces of the human body, and to inform the clinical management of chronic infectious diseases such as human immunodeficiency virus (HIV). Taken together, these approaches are dramatically accelerating the pace of human disease research and are already impacting patient care.

Highlights

Inherited complex diseases have proved the most pervasive yet recalcitrant examples of human disease to reveal their genomic secrets
A variety of techniques that target human gene sequences for differential capture from a genomic sample, coupled with next-generation, massively parallel DNA sequencing instruments, is rapidly supplanting the combination of polymerase chain reaction and capillary sequencing to discover coding variants in medically relevant samples. These studies are most appropriate for the sample numbers necessary to identify both common and rare single nucleotide variants, as well as small insertion or deletion events, which may cause complex inherited diseases
With the development and publication of several methods that can selectively isolate sequences of interest from a genomic DNA sample, there are high-throughput methods available for variant discovery within genomic regions identified by genomewide association studies (GWAS) or by candidate gene approaches

Summary

Introduction

Inherited complex diseases have proved the most pervasive yet recalcitrant examples of human disease to reveal their genomic secrets. A variety of techniques that target human gene sequences for differential capture from a genomic sample, coupled with next-generation, massively parallel DNA sequencing instruments, is rapidly supplanting the combination of polymerase chain reaction and capillary sequencing to discover coding variants in medically relevant samples.

Results

Conclusion