Whole genome sequencing and its applications in medical genetics

Abstract

Fundamental improvement was made for genome sequencing since the next-generation sequencing (NGS) came out in the 2000s. The newer technologies make use of the power of massively-parallel short-read DNA sequencing, genome alignment and assembly methods to digitally and rapidly search the genomes on a revolutionary scale, which enable large-scale whole genome sequencing (WGS) accessible and practical for researchers. Nowadays, whole genome sequencing is more and more prevalent in detecting the genetics of diseases, studying causative relations with cancers, making genome-level comparative analysis, reconstruction of human population history, and giving clinical implications and instructions. In this review, we first give a typical pipeline of whole genome sequencing, including the lab template preparation, sequencing, genome assembling and quality control, variants calling and annotations. We compare the difference between whole genome and whole exome sequencing (WES), and explore a wide range of applications of whole genome sequencing for both mendelian diseases and complex diseases in medical genetics. We highlight the impact of whole genome sequencing in cancer studies, regulatory variant analysis, predictive medicine and precision medicine, as well as discuss the challenges of the whole genome sequencing.

Graphical abstract

Keywords

whole genome sequencing / whole exome sequencing / next-generation sequencing / non-coding / regulatory variant

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ACKNOWLEDGEMENTS

This research was partially supported by the National Basic Research Program of China (No. 2012CB316504), the National High Technology Research and Development Program of China (No. 2012AA020401), the National Natural Science Foundation of China (Nos. 61573207 and 61175002) and Beijing Collaborative Innovation Center for Cardiovascular Disorders.

COMPLIANCE WITH ETHICS GUIDELINES

All authors confirm the absence of previous similar or simultaneous publications, their inspection of the manuscript, their substantial contribution to the work, and their agreement to submission.

This article does not contain any studies with human or animal subjects performed by any of the authors.

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