PacBio long-read amplicon sequencing enables scalable high-resolution population allele typing of the complex CYP2D6 locus.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
25 02 2022
25 02 2022
Historique:
received:
14
08
2021
accepted:
01
02
2022
entrez:
26
2
2022
pubmed:
27
2
2022
medline:
5
4
2022
Statut:
epublish
Résumé
The CYP2D6 enzyme is estimated to metabolize 25% of commonly used pharmaceuticals and is of intense pharmacogenetic interest due to the polymorphic nature of the CYP2D6 gene. Accurate allele typing of CYP2D6 has proved challenging due to frequent copy number variants (CNVs) and paralogous pseudogenes. SNP-arrays, qPCR and short-read sequencing have been employed to interrogate CYP2D6, however these technologies are unable to capture longer range information. Long-read sequencing using the PacBio Single Molecule Real Time (SMRT) sequencing platform has yielded promising results for CYP2D6 allele typing. However, previous studies have been limited in scale and have employed nascent data processing pipelines. We present a robust data processing pipeline "PLASTER" for accurate allele typing of SMRT sequenced amplicons. We demonstrate the pipeline by typing CYP2D6 alleles in a large cohort of 377 Solomon Islanders. This pharmacogenetic method will improve drug safety and efficacy through screening prior to drug administration.
Identifiants
pubmed: 35217695
doi: 10.1038/s42003-022-03102-8
pii: 10.1038/s42003-022-03102-8
pmc: PMC8881578
doi:
Substances chimiques
Cytochrome P-450 CYP2D6
EC 1.14.14.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
168Subventions
Organisme : NIAID NIH HHS
ID : U19 AI129392
Pays : United States
Informations de copyright
© 2022. The Author(s).
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