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Identification of a novel HLA-B allele, HLA-B*40:238,
in a Taiwanese individual
H.-L. Lee1 | S.-K. Lai1,2 | P.-L. Chen3,4 | C.-C. Chu1
Department of Medical Research, Mackay
Memorial Hospital, New Taipei City, Taiwan
Institute of Molecular Medicine, National Taiwan
University College of Medicine, Taipei, Taiwan
Department of Medical Genetics, National
Taiwan University Hospital, Taipei, Taiwan
The HLA-B*40:238 allele has one non-synonymous transversion from HLA-B
*40:01:01 at nucleotide position 484.
HLA-B*40:238, new allele, sequencing-based typing
Graduate Institute of Medical Genomics and
Proteomics, National Taiwan University, Taipei,
Chen-Chung Chu, PhD, Department of Medical
Research, Mackay Memorial Hospital, #45,
Minsheng Road, Tamshui District, New Taipei
City 25160, Taiwan.
Pei-Lung Chen, MD, PhD, Department of Medical
Genetics, National Taiwan University Hospital,
#8, Zhongshan S. Rd., Taipei City 10041, Taiwan.
Funding information
Mackay Memorial Hospital, Grant/Award number:
The HLA-B*40:238 allele was found in an association study
between human leukocyte antigen (HLA) and antithyroid
drug-induced agranulocytosis.1 The allele, initially genotyped
in a Graves’ disease patient showed one mismatched nucleotide within the combined sequence pattern of B*40:01:01 and
B*13:01:01 using SeCore HLA Sequence-based typing kit
(Life Technologies Corporation, Brown Deer, Wisconsin). To
determine which allele the mismatch belonged to, polymerase
chain reaction (PCR) was carried out to amplify exon 2 to
exon 4 of the HLA-B region with dimorphic forward primers
as described by Cereb et al.2 PCR products were subsequently
cloned using a TA-cloning kit (RBC TA-cloning kit, RBC
Bioscience, New Taipei City, Taiwan). Six clones with this
mutation were obtained and sequenced in both directions
using Big Dye Terminator Cycle Sequencing Ready Reaction
Kit (Applied Biosystems, Foster City, California).
The sequence resulted to the novel allele, B*40:238,
which was identical to B*40:01:01 in exon 2 and 4 but
with one non-synonymous transversion (A!T) at nucleotide position 484 in exon 3. It causes an amino acid
Partial alignment of nucleotide
sequences of B*40:01:01 with B*13:01:01,
B*40:238 and B*07:238 from Codon 130 to
Codon 160. The B*40:01:01 sequence is used
as reference sequence. Dashes indicate
nucleotide identity with B*40:01:01
change at codon 138 (ACG!TCG) (Figure 1). A search
for the presence of this codon polymorphism in other
HLA alleles was undertaken using the IPD-IMGT/HLA
database3 (Release 3.28.0 April 2017) which indicated that
the same codon was also seen in the B*07:238 allele
(Figure 1). Since B*07:238 is not a common allele in Asia,
it is unlikely that B*40:238 was the result of a gene conversion between B*07:238 and B*40:01:01, on the other
hand, since B*40:01:01 is the most prominent HLA-B
allele in Taiwan Han Chinese (21.1%),4 it is most likely
that the B*40:238 allele was generated by a point mutation
in the B*40:01:01 allele.
Further, the nucleotide substitutions in B*40:238 correspond to an amino acid change from Threonine to Serine at
codon 138. Due to the strong structural homology between all
HLA class I molecules, it is believed that amino acid residue
138 does not contribute to the peptide-binding pockets on the
MHC class I molecules,5 and is consequently not expected to
alter the specific peptide-binding profile of B*40:238.
The name B*40:238 has been officially assigned by the
World Health Organization (WHO) Nomenclature Committee in March 2013. This follows the agreed policy that subject to the conditions stated in the most recent Nomenclature
Report6 names will be assigned to new sequences as they are
identified. Lists of such new names will be published in the
following WHO Nomenclature Report. The nucleotide
sequence data of the new allele has appeared in the EMBL,
GenBank and DDBJ Nucleotide Sequence Database under
the accession number KC776574.
This work was supported by grant MMH-104-047 from the
Mackay Memorial Hospital.
Conflict of interest
The authors declare no potential conflict of interests.
1. Chen PL, Shih SR, Wang PW, et al. Genetic determinants of antithyroid
drug-induced agranulocytosis by human leukocyte antigen genotyping and
genome-wide association study. Nat Commun. 2015;6:7633.
2. Cereb N, Maye P, Lee S, Kong Y, Yang S. Locus-specific amplification of
HLA class I gene from genomic DNA:locus-specific sequences in the first
and third introns of HLA-A,-B and -C alleles. Tissue Antigens.
3. Robinson J, Halliwell JA, Hayhurst JD, Flicek P, Parham P, Marsh SG. The
IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res.
2015;43(Database issue):D423-D431.
4. Chen PL, Fann CS, Chu CC, et al. Comprehensive genotyping in two homogeneous graves' disease samples reveals major and novel HLA association
alleles. PLoS One. 2011;6:e16635.
5. Elsner HA, DeLuca D, Strub J, Blasczyk R. HistoCheck: rating of HLA class
I and II mismatches by an internet-based software tool. Bone Marrow Transplant. 2004;33:165-169.
6. Marsh SG, Albert ED, Bodmer WF, et al. Nomenclature for factors of the
HLA system, 2010. Tissue Antigens. 2010;75:291-455.
How to cite this article: Lee H-L, Lai S-K, Chen P-L,
Chu C-C. Identification of a novel HLA-B allele,
HLA-B*40:238, in a Taiwanese individual. HLA.
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