Comparison of genome sequencing and clinical genotyping for pharmacogenes.
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.
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
W
W
Yang
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
G
G
Wu
Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
U
U
Broeckel
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
C A
CA
Smith
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
V
V
Turner
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
C E
CE
Haidar
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
S
S
Wang
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
R
R
Carter
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
S E
SE
Karol
Hartwell Center, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
G
G
Neale
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
K R
KR
Crews
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
J J
JJ
Yang
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
C G
CG
Mullighan
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
J R
JR
Downing
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
W E
WE
Evans
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. mary.relling@stjude.org.
M V
MV
Relling
D059472:Exome / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D060005:Genotyping Techniques; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*