Format

Send to

Choose Destination
Clin Pharmacol Ther. 2016 Oct;100(4):380-8. doi: 10.1002/cpt.411. Epub 2016 Aug 18.

Comparison of genome sequencing and clinical genotyping for pharmacogenes.

Author information

1
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
2
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
3
Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
4
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
5
Hartwell Center, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
6
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. mary.relling@stjude.org.

Abstract

We compared whole exome sequencing (WES, n = 176 patients) and whole genome sequencing (WGS, n = 68) and clinical genotyping (DMET array-based approach) for interrogating 13 genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. We focused on 127 CPIC important variants: 103 single nucleotide variations (SNV), 21 insertion/deletions (Indel), HLA-B alleles, and two CYP2D6 structural variations. WES and WGS provided interrogation of nonoverlapping sets of 115 SNV/Indels with call rate >98%. Among 68 loci interrogated by both WES and DMET, 64 loci (94.1%, confidence interval [CI]: 85.6-98.4%) showed no discrepant genotyping calls. Among 66 loci interrogated by both WGS and DMET, 63 loci (95.5%, CI: 87.2-99.0%) showed no discrepant genotyping calls. In conclusion, even without optimization to interrogate pharmacogenetic variants, WES and WGS displayed potential to provide reliable interrogation of most pharmacogenes and further validation of genome sequencing in a clinical lab setting is warranted.

PMID:
27311679
PMCID:
PMC5684873
DOI:
10.1002/cpt.411
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center