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Whole-genome and whole-exome sequencing in neurological diseases

Nature Reviews Neurology volume 8, pages 508–517 (2012)Cite this article

Subjects

Abstract

Genetic risk factors that underlie many rare and common neurological disorders remain poorly understood because of the multifactorial and heterogeneous nature of these complex traits. With the decreasing cost of massively parallel sequencing technologies, whole-genome and whole-exome sequencing will soon allow the characterization of the full spectrum of sequence and structural variants present in each individual. Methods are being developed to parse the huge amount of genomic data and to sift out which variants are associated with diseases. Numerous challenges are inherent in the identification of rare and common variants that have a role in complex neurological diseases, and tools are being developed to overcome these challenges. Given that genomic data will soon be the main driver towards the goal of personalized medicine, future developments in the production and interpretation of data, as well as in ethics and counselling, will be needed for whole-genome and whole-exome sequencing to be used as informative tools in a clinical setting.

Key Points

  • Whole-genome and whole-exome sequencing is becoming increasingly affordable for use in a clinical setting

  • Recent studies demonstrate successes in applying whole-genome or whole-exome sequencing to disease gene discovery and clinical diagnosis of complex neurological diseases, but they also highlight major challenges in data interpretation

  • The various tools and methods that have been developed to process next-generation sequencing data and to parse the list of genomic variants must be carefully evaluated for clinical use

  • The majority of genomic variants do not have known or confirmed clinical effects, and caution is needed in the interpretation and reporting of genetic results

  • Basic guidelines have been drawn up for the implementation of genetic testing in a clinical setting; these guidelines are likely to be reviewed and changed over time

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Figure 1: Steps in the generation of whole-genome or whole-exome sequencing data for analysis.
Figure 2: Suggested steps in filtering of genomic variants for the identification of Mendelian disease mutations or rare variants with large effects.

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Authors and Affiliations

  1. Human Genetics, Genome Institute of Singapore, A*STAR, 60 Biopolis Street, Genome #02-01, 138672, Singapore

    Jia-Nee Foo & Jian-Jun Liu

  2. Department of Neurology, National Neuroscience Institute, Duke-National University of Singapore Graduate Medical School, Singapore General Hospital, Block 1 Level 3, Outram Road, 169108, Singapore

    Eng-King Tan

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  1. Jia-Nee Foo
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J.-N. Foo researched the data for and wrote the article. J.-J. Liu and E.-K. Tan made substantial contributions to discussions of the content, and reviewed and edited the manuscript before submission.

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Correspondence to Eng-King Tan.

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Foo, JN., Liu, JJ. & Tan, EK. Whole-genome and whole-exome sequencing in neurological diseases. Nat Rev Neurol 8, 508–517 (2012). https://doi.org/10.1038/nrneurol.2012.148

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