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How to identify pathogenic mutations among all those variations: Variant annotation and filtration in the genome sequencing era
Journal article   Open access   Peer reviewed

How to identify pathogenic mutations among all those variations: Variant annotation and filtration in the genome sequencing era

D. Salgado, M.I. Bellgard, J-P Desvignes and C. Beroud
Human Mutation, Vol.37(12), pp.1272-1282
2016
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Abstract

High-throughput sequencing technologies have become fundamental for the identification of disease-causing mutations in human genetic diseases both in research and clinical testing contexts. The cumulative number of genes linked to rare diseases is now close to 3,500 with more than 1,000 genes identified between 2010 and 2014 because of the early adoption of Exome Sequencing technologies. However, despite these encouraging figures, the success rate of clinical exome diagnosis remains low due to several factors including wrong variant annotation and nonoptimal filtration practices, which may lead to misinterpretation of disease-causing mutations. In this review, we describe the critical steps of variant annotation and filtration processes to highlight a handful of potential disease-causing mutations for downstream analysis. We report the key annotation elements to gather at multiple levels for each mutation, and which systems are designed to help in collecting this mandatory information. We describe the filtration options, their efficiency, and limits and provide a generic filtration workflow and highlight potential pitfalls through a use case.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.189 Genome Studies
1.189.597 Genetic Testing
Web Of Science research areas
Genetics & Heredity
ESI research areas
Molecular Biology & Genetics
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