EDS files (raw data) from QuantStudio for Validation of Single Nucleotide Variant Assays for Human Leukocyte Antigen Haplotypes HLA-B*15:02 and HLA-A*31:01 Across Diverse Ancestral Backgrounds

The human
leukocyte antigen haplotypes HLA-B*15:02 and HLA-A*31:01 have
been linked to life-threatening adverse drug reactions to the anticonvulsants
carbamazepine and oxcarbazepine. Identification of these haplotypes via
pharmacogenetic techniques facilitates implementation of precision medicine to
prevent such reactions. Using reference samples from diverse ancestral origins,
we investigated the test analytical validity (i.e., ability to detect whether
or not the haplotypes were present or absent) of TaqMan assays for single
nucleotide variants previously identified as potentially being able to “tag”
these haplotypes. A TaqMan custom assay for rs10484555 and an inventoried assay
for rs17179220 and were able to identify with 100% sensitivity and 100% specificity
HLA-B*15:02 and HLA-A*31:01 respectively. A custom assay for
rs144012689 that takes into account a neighboring single nucleotide variant with
manual calling was also able to identify HLA-B*15:02 with 100%
sensitivity and 100% specificity. A custom assay for rs106235 identified HLA-A*31:01
with 100% sensitivity and 95% specificity. The slight reduction in specificity
for the latter was owing to another haplotype (HLA-A*33:03) also being
detected. While any positive call using the rs106235 assay could therefore be
further investigated, as the presence of the HLA-A*31:01 haplotype
confers adverse drug reaction risk, the absence of false negatives (indexed by
sensitivity) is more important than false positives. In summary, we present
validated TaqMan assay methodology for efficient detection of HLA haplotypes HLA-B*15:02
and HLA-A*31:01. Our data are relevant for other genotyping
technologies that identify, or have the potential to identify, these haplotypes
using single nucleotide variants.

These data files are the output from QuantStudio, the raw data from this study.