GeneBreaker: Variant simulation to improve the diagnosis of Mendelian rare genetic diseases.
Hum Mutat
; 42(4): 346-358, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33368787
ABSTRACT
Mendelian rare genetic diseases affect 5%-10% of the population, and with over 5300 genes responsible for â¼7000 different diseases, they are challenging to diagnose. The use of whole-genome sequencing (WGS) has bolstered the diagnosis rate significantly. The effective use of WGS relies on the ability to identify the disrupted gene responsible for disease phenotypes. This process involves genomic variant calling and prioritization, and is the beneficiary of improvements to sequencing technology, variant calling approaches, and increased capacity to prioritize genomic variants with potential pathogenicity. As analysis pipelines continue to improve, careful testing of their efficacy is paramount. However, real-life cases typically emerge anecdotally, and utilization of clinically sensitive and identifiable data for testing pipeline improvements is regulated and limiting. We identified the need for a gene-based variant simulation framework that can create mock rare disease scenarios, utilizing known pathogenic variants or through the creation of novel gene-disrupting variants. To fill this need, we present GeneBreaker, a tool that creates synthetic rare disease cases with utility for benchmarking variant calling approaches, testing the efficacy of variant prioritization, and as an educational mechanism for training diagnostic practitioners in the expanding field of genomic medicine. GeneBreaker is freely available at http//GeneBreaker.cmmt.ubc.ca.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Genômica
/
Doenças Raras
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Mutat
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá