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Whole exome and genome sequencing for Mendelian immune disorders: from molecular diagnostics to new disease variant and gene discovery

Publication: LymphoSign Journal
22 November 2016

Abstract

Whole exome and whole genome sequencing are next generation sequencing (NGS) applications that enable investigation of all coding variants (around 20 000) or all variants (around 4 million) in the human genome. They provide an extremely powerful tool for detecting variants with an established implication in Mendelian disorders as well as for discovering new disease variants and genes. The large number of variants generated requires elaborate databases, prediction models, and integrated workflows to identify which variants are more likely to contribute to disease. We discuss the whole exome and whole genome options, review the sequencing platforms and variant calling pipelines available for different variant types, and devote most of the review to how genetic variants can be annotated and prioritized to identify the ones likely contributing to disorder. The application focus will be Mendelian disorders; disorders caused by rare or common variants with a more complex genetic architecture will only be discussed briefly. For variant annotation and interpretation, we will concentrate on smaller variants (substitutions, insertions, and deletions), only briefly reviewing structural and copy number variation.

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cover image LymphoSign Journal
LymphoSign Journal
Volume 3Number 4December 2016
Pages: 135 - 158

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Received: 26 September 2016
Accepted: 22 November 2016
Accepted manuscript online: 22 November 2016

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Daniele Merico [email protected]
Deep Genomics Inc., Toronto, ON
The Centre for Applied Genomics (TCAG), The Hospital for Sick Children (SickKids), Toronto, ON

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