Jan 20, 2012

Disease gene identification strategies for exome sequencing

European Journal of Human Genetics : EJHG
Christian GilissenJoris A Veltman

Abstract

Next generation sequencing can be used to search for Mendelian disease genes in an unbiased manner by sequencing the entire protein-coding sequence, known as the exome, or even the entire human genome. Identifying the pathogenic mutation amongst thousands to millions of genomic variants is a major challenge, and novel variant prioritization strategies are required. The choice of these strategies depends on the availability of well-phenotyped patients and family members, the mode of inheritance, the severity of the disease and its population frequency. In this review, we discuss the current strategies for Mendelian disease gene identification by exome resequencing. We conclude that exome strategies are successful and identify new Mendelian disease genes in approximately 60% of the projects. Improvements in bioinformatics as well as in sequencing technology will likely increase the success rate even further. Exome sequencing is likely to become the most commonly used tool for Mendelian disease gene identification for the coming years.

  • References82
  • Citations220

Citations

Mentioned in this Paper

Genome-Wide Association Study
Genome
Pathogenic Organism
Bio-Informatics
DNA Resequencing
Genomics
Sequencing
Massively-Parallel Sequencing
Atypical Mycobacteriosis, Familial
Sequence Determinations, DNA

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