Reanalysing genomic data by normalized coverage values uncovers CNVs in bone marrow failure gene panels.
Genetic testing
Medical genomics
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
2019
2019
Historique:
received:
19
10
2018
accepted:
04
10
2019
entrez:
17
12
2019
pubmed:
17
12
2019
medline:
17
12
2019
Statut:
epublish
Résumé
Inherited bone marrow failure syndromes (IBMFSs) are genetically heterogeneous disorders with cytopenia. Many IBMFSs also feature physical malformations and an increased risk of cancer. Point mutations can be identified in about half of patients. Copy number variation (CNVs) have been reported; however, the frequency and spectrum of CNVs are unknown. Unfortunately, current genome-wide methods have major limitations since they may miss small CNVs or may have low sensitivity due to low read depths. Herein, we aimed to determine whether reanalysis of NGS panel data by normalized coverage value could identify CNVs and characterize them. To address this aim, DNA from IBMFS patients was analyzed by a NGS panel assay of known IBMFS genes. After analysis for point mutations, heterozygous and homozygous CNVs were searched by normalized read coverage ratios and specific thresholds. Of the 258 tested patients, 91 were found to have pathogenic point variants. NGS sample data from 165 patients without pathogenic point mutations were re-analyzed for CNVs; 10 patients were found to have deletions. Diamond Blackfan anemia genes most commonly exhibited heterozygous deletions, and included
Identifiants
pubmed: 31839986
doi: 10.1038/s41525-019-0104-9
pii: 104
pmc: PMC6901453
doi:
Types de publication
Journal Article
Langues
eng
Pagination
30Informations de copyright
© The Author(s) 2019.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing interests.
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