Marrow Hematopoietic Stem Cell Donor Research Articles

Identification of a novel HLA allele, HLA-B*15:416, in a bone marrow hematopoietic stem cell donor.

The novel HLA-B*15:416 allele differs from HLA-B*15:01:01:01 by a single nucleotide substitution at codon 114.

Deduced probable HLA-C*07:359-associated human leukocyte antigen haplotypes found by case analysis of Taiwanese unrelated bone marrow hematopoietic stem cell donors

ObjectivesHLA-C*07:359 is a low-incidence allele in the human leukocyte antigen (HLA)-C locus. The objective of this study is to report the ethnicity and haplotypes of HLA-C*07:359 that were found during an analysis of Taiwanese unrelated bone marrow hematopoietic stem cell donors. Materials and methodsA sequence-based typing method was employed to confirm low-incidence alleles. Polymerase chain reaction was performed to amplify exon 2 and exon 3 of the HLA-A, HLA-B, and HLA-C loci, as well as exon 2 of the HLA-DRB1 locus, using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits, according to the manufacturer's protocols. The potential unrelated bone marrow stem cell donors investigated here are individuals with Taiwanese ethnicity who are participating in the Tzu Chi Bone Marrow Donor Registry. ResultsThe DNA sequence of C*07:359 is identical to that of C*07:02:01:01 in exons 2, 3, and 4 except at residue 862, where the G of C*07:02:01:01 is substituted by the A of C*07:359. The nucleotide exchange leads to an amino acid replacement at codon 264, where the glutamic acid of C*07:02:01:01 is replaced by the lysine of C*07:359. We deduced a probable HLA-B and HLA-C haplotype that is associated with C*07:359 in Taiwanese, namely B*39-C*07:359. ConclusionInformation on the ethnicity of the C*07:359 allele and its deduced probable HLA haplotypes that are associated with the low-incidence C*07:359 allele reported here are of value to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to determine a strategy for finding compatible donors using unrelated bone marrow donor registries when patients carry this uncommon HLA allele.

A deduced probable HLA-DRB1*16:35-associated HLA haplotype (A*11-B*13-DRB1*16:35) found in a case analysis of two Taiwanese unrelated bone marrow hematopoietic stem cell donors

ObjectiveHLA-DRB1*16:35 is a low incidence allele in the HLA-DRB1 locus. The objective of this study is to report the ethnicity of DRB1*16:35 and its deduced probable HLA associated haplotype in two Taiwanese unrelated bone marrow hematopoietic stem cell donors and to determine its variation from DRB1*16:02:01 and DRB1*16:01:01. Materials and MethodsA sequence-based typing method was employed to confirm the low incidence allele DRB1*16:35. Polymerase chain reaction was performed to amplify exon 2 and exon 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced employing BigDye Terminator Cycle Sequencing Ready Reaction kits in both directions according to the manufacturer's protocols. ResultsThe DNA sequence of DRB1*16:35 is identical to DRB1*16:02:01 in exons 2, except for residue 364 where the C of DRB1*16:02:01 is replaced by the T of DRB1*16:35 (codon 93, CGG->TGG). The nucleotide exchange leads to an amino acid alteration to the protein sequence of DRB1*16:02:01 at residue 93 where the arginine (R) of DRB1*16:02:01 is changed to the tryptophan (W) of DRB1*16:35. We deduced the probable HLA haplotype in association with DRB1*16:35 in Taiwanese to be A*11-B*13-DRB1*16:35. ConclusionInformation on the deduced probable HLA haplotype in association with the low incidence DRB1*16:35 allele that we report here is of value for HLA testing laboratories for reference purposes. In addition, it can be used by stem cell transplantation donor search coordinators to determine a strategy for finding compatible donors in unrelated bone marrow donor registries when a patient has this uncommon HLA allele.

Identification of a novel HLA-A*02 variant, HLA-A*02:586, in a Taiwanese bone marrow hematopoietic stem cell donor.

One nucleotide substitution at residue 179 of the HLA-A*02:07:01 results in a new allele, HLA-A*02:586.

HLA-A*02:06:21, a novel variant of HLA-A*02:06, discovered in a Taiwanese bone marrow hematopoietic stem cell donor.

One nucleotide substitution at residue 318 of the HLA-A*02:06:01:01 results in a new allele, HLA-A*02:06:21.

HLA‐B*40:306, a novel variant of HLA‐B*40, discovered in a Taiwanese bone marrow hematopoietic stem cell donor

One nucleotide substitution at residue 308 of the HLA-B*40:06:01:01 results in a new allele, HLA-B*40:306.

Two deduced probable HLA-A*24:287-associated HLA haplotypes (A*24:287-B*40-DRB1*15 and A*24:287-B*58-DRB1*03:01) found in Taiwanese unrelated hematopoietic bone marrow stem cell donors-case analysis

ObjectiveHLA-A*24:287 is a low incidence allele in the HLA-A locus. The objective of this study is to report the ethnicity of A*24:287 and its deduced probable human leukocyte antigen (HLA)-associated haplotypes in Taiwanese unrelated bone marrow hematopoietic stem cell donors. Materials and methodsA sequence-based typing method was employed to confirm the low incidence allele A*24:287. Polymerase chain reaction was performed to amplify exon 2 and exon 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced employing BigDye Terminator Cycle Sequencing Ready Reaction kits in both directions according to the manufacturer's protocols. ResultsThe DNA sequence of A*24:287 is identical to A*24:02:01:01 in exons 2 and 3, except for residue 617 where C is changed to G (codon 182, ACG->AGG). The nucleotide exchange leads to an amino acid alteration to the protein sequence of A*24:02:01:01 at residue 182 where the threonine of A*24:02:01:01 is changed to the arginine of A*24:287. We deduced the probable HLA haplotypes in association with A*24:287 in Taiwanese to be A*24:287-B*40-DRB1*15 and A*24:287-B*58-DRB1*03:01. ConclusionInformation on the deduced probable HLA haplotypes in association with the low incidence A*24:287 allele that we report here are of value for HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to determine a strategy for finding compatible donors in unrelated bone marrow donor registries when a patient has this uncommon HLA allele.

HLA-A*33-B*58:45-DRB1*03, a deduced probable human leukocyte antigen haplotype associated with a human leukocyte antigen low-incidence allele B*58:45 in Taiwanese unrelated hematopoietic bone marrow stem cell donors

ObjectiveHLA-B*58:45 is a low-incidence allele in the human leukocyte antigen-B (HLA) locus. The aim of this study is to confirm the ethnicity of B*58:45 and its deduced probable HLA-associated haplotype in Taiwanese unrelated bone marrow hematopoietic stem cell donors. Materials and methodsA total of 40,000 healthy unrelated volunteer bone marrow stem cell donors (aged, 20–45 years) were tested using a sequence-based typing method. We confirmed the low-incidence allele B*58:45 in Taiwanese donors. Polymerase chain reaction was performed to amplify exon 2 and exon 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions with the BigDye Terminator Cycle Sequencing Ready Reaction Kit according to the manufacturer's protocols. ResultsThe DNA sequence of B*58:45 is identical to B*58:01:01 in exon 2 and exon 3 except for residue 595, where G is changed to A (codon 175, GGG→AGG). The nucleotide replacement causes an amino acid change at codon 175 where G (glycine) of B*58:01:01 is replaced by R (arginine). We deduced the probable HLA haplotype associated with B*58:45 in Taiwanese donors to be A*33-B*58:45-DRB1*03. ConclusionInformation on this deduced probable HLA haplotype in association with the low-incidence B*58:45 allele is of value for HLA testing laboratories for reference purposes and can help bone marrow donor registries find compatible donors for patients with this uncommon HLA allele.

Deduced probable HLA-B*40:01:35-associated HLA haplotype (A*24-B*40:01:35-DRB1*11) found in a Taiwanese unrelated hematopoietic bone marrow stem cell donor

ObjectiveHuman leukocyte antigen (HLA)-B*40:01:35 is a low incidence allele in the HLA-B locus. The objective of this study is to report the ethnicity of B*40:01:35 and its deduced probable HLA associated haplotype in a Taiwanese unrelated bone marrow hematopoietic stem cell donor. Materials and methodsA sequence-based typing method was employed to confirm the low incidence allele B*40:01:35. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced using the BigDye Terminator Cycle Sequencing Ready Reaction kit in both directions according to the manufacturer's protocols. ResultsThe DNA sequence of B*40:01:35 is identical to B*40:01:01 in exons 2 and 3, except for residue 324 where C is changed to T (codon 84, TAC→TAT). The nucleotide exchange does not cause amino acid alteration to the protein sequence of B*40:01:01 due to the silent mutation. We deduced the probable HLA haplotype in association with B*40:01:35 in Taiwanese to be A*24-B*40:01:35-DRB1*11. ConclusionInformation on the deduced probable HLA haplotype in association with the low incidence B*40:01:35 allele that we report here is of value for HLA testing laboratories for reference purposes. In addition, it can be used by stem cell transplantation donor search coordinators to determine a strategy for finding compatible donors in unrelated bone marrow donor registries when a patient has this uncommon HLA allele.

The deduced probable human leukocyte antigen haplotype associated with human leukocyte antigen low incidence allele B∗40:36 (A∗02-B∗40:36-DRB1∗12) in Taiwanese unrelated hematopoietic bone marrow stem cell donors

ObjectiveHuman leukocyte antigen (HLA)-B∗40:36 is a low incidence allele in the HLA-B locus. This study reports the ethnicity of B∗40:36 and the deduced probable HLA haplotype associated with HLA-B∗40:36 in Taiwanese unrelated bone marrow hematopoietic stem cell donors. Materials and methodsA sequence-based typing method was employed to confirm that the low incidence allele was present. Polymerase chain reaction was performed to amplify exons 2 and 3 in the HLA-A and HLA-B loci and exon 2 in the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced using the BigDye Terminator Cycle Sequencing Ready Reaction Kit in both directions. ResultsThe DNA sequence of B∗40:36 is identical to B∗40:01:01 in exons 2 and 3, except for a one nucleotide substitution at residue 419 (A→T), which results in a one amino acid replacement at position 116 (Y→F; tyrosine→phenylalanine). We deduced the probable HLA haplotype in an association with B∗40:36 in Taiwanese to be A∗02-B∗40:36-DRB1∗12. ConclusionInformation on the deduced probable HLA haplotype in an association with the low incidence B∗40:36 allele that we report here is of value for HLA testing laboratories for reference purposes. In addition, it can be used by stem cell transplantation donor search coordinators to determine the likelihood of finding compatible donors in unrelated bone marrow donor registries when a patient has this uncommon HLA allele.

Recognition of the three deduced probable HLA haplotypes that are associated with HLA-C∗16:04:01 (A∗33:03-B∗44:02-C∗16:04:01-DRB1∗11:04:01 and A∗24-B∗44:02-C∗16:04:01-DRB1∗11:04) and HLA-B∗15:109 (A∗11-B∗15:109-DRB1∗04) in Taiwanese unrelated hematopoietic stem cell donors

ObjectiveHLA-C∗16:04:01 and HLA-B∗15:109 are two uncommon alleles at the HLA-C locus and HLA-B locus, respectively. The objective of this study is to report the deduced probable human leukocyte antigen (HLA) haplotypes associated with HLA-C∗16:04:01 and HLA-B∗15:109 among Taiwanese unrelated bone marrow hematopoietic stem cell donors. Materials and methodsA sequence-based typing method was employed to confirm the two low incidence alleles observed. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A, and HLA-B loci with group-specific primer sets. Amplicons were sequenced using a BigDye Terminator Cycle Sequencing Ready Reaction Kit in both directions according to the manufacturer's protocols. ResultsThe DNA sequence of C∗16:04:01 is identical to that of C∗16:01:01 in exons 2 and 3, except for two nucleotide substitutions at residues 538 (C->T) and 539 (A->G), which results in a single amino acid replacement at position 156 (glutamine->tryptophan). We deduced two probable HLA haplotypes that are found in association with C∗16:04:01 as A∗33:03-B∗44:02-C∗16:04:01-DRB1∗11:04 and A∗24-B∗44:02-C∗16:04:01-DRB1∗11:04. The DNA sequence of B∗15:109 is identical to B∗15:27:01 in exons 2 and 3 except for one nucleotide substitution at residue 200 (C->T), which results in a single amino acid replacement at position 43 (proline->leucine). A probable HLA haplotype associated with B∗15:109 was deduced to be A∗11-B∗15:109-DRB1∗04. ConclusionInformation on the deduced HLA haplotypes that are found in association with the rare C∗16:04:01 and B∗15:109 alleles that we report here is useful for reference purposes at HLA testing laboratories and will help stem cell transplantation donor search coordinators when they are determining the likelihood of finding a compatible donor for patients bearing these two uncommon HLA alleles from unrelated bone marrow donor registries.

An HLA-A*11 variant, A*11:166, revealed in a Taiwanese unrelated bone marrow hematopoietic stem cell donor.

One nucleotide replacement in codon 35 of the human leukocyte antigen HLA-A*11:01:01 results in a new allele, HLA-A*11:166.

Recognition of the deduced probable HLA haplotypes associated with HLA low incidence alleles B∗13:50 (A∗11:02-B∗13:50-DRB1∗07:01) and B∗51:39 (A∗02-B∗51:39-DRB1∗15; and A∗11-B∗51:39-DRB1∗15) in Taiwanese unrelated hematopoietic stem cell donors

ObjectivesHLA-B∗13:50 and -B∗51:39 are two low incidence alleles in the HLA-B locus. The objective of this study is to report the deduced probable human leukocyte antigen (HLA) haplotypes in association with HLA-B∗13:50 and -B∗51:39 in Taiwanese unrelated bone marrow hematopoietic stem cell donors. Materials and MethodsA sequence-based typing method was used to confirm the two low incidence alleles observed. Polymerase chain reaction was performed to amplify exons 2 and 3 in the HLA-A and HLA-B loci and exon 2 in the HLA-DRB1 locus with group-specific primer sets. Amplicons were sequenced using the BigDye Terminator Cycle Sequencing Ready Reaction Kit in both directions according to the manufacturer's protocols. ResultsThe DNA sequence of B∗13:50 is identical to B∗13:01:01 in exons 2 and 3, except for a one nucleotide substitution at residue 482 (A→T), which results in a one amino acid replacement at position 137 (aspartic acid→valine). We deduced the probable HLA haplotype in association with B∗13:50 in Taiwanese as A∗11:02-B∗13:50-DRB1∗07:01. The DNA sequence of B∗51:39 is identical to B∗51:01:03 in exons 2 and 3 except for two nucleotide exchanges at residue 226 (A→G) and residue 228 (A→G), which result in a one amino acid substitution at position 52 (isoleucine→valine).The probable HLA haplotypes associated with B∗51:39 in Taiwanese may be deduced as A∗02-B∗51:39-DRB1∗15 and A∗11-B∗51:39-DRB1∗15. ConclusionInformation on the deduced HLA haplotypes in association with the low incidence B∗13:50 and B∗51:39 alleles that we report here is valuable for HLA testing laboratories for reference purposes and for stem cell transplantation donor search coordinators, to determine the likelihood of finding compatible donors in unrelated bone marrow donor registries for patients carrying these two uncommon HLA alleles.

Recognition of the three deduced probable human leukocyte antigen haplotypes in association with HLA-A∗31:30 (A∗31:30-B∗15-DRB1∗14) and HLA-B∗40:55 (A∗02:07-B∗40:55-DRB1∗04:05 and A∗26:01-B∗40:55-DRB1∗09:01) in a Taiwanese population

ObjectivesHLA-A∗31:30 and HLA-B∗40:55 are two rarely observed alleles in the HLA-A locus and HLA-B locus, respectively. The objective of this study is to report three deduced probable human leukocyte antigen (HLA) haplotypes in association with HLA-A∗31:30 and HLA-B∗40:55 in unrelated bone marrow hematopoietic stem cell donors. Materials and methodsA sequence-based typing method was used to confirm the two low-incidence alleles observed. A polymerase chain reaction was performed to amplify exons 2, 3, and 4 of the HLA-A, -B, and -C loci and exon 2 of the HLA-DRB1 locus with group-specific primer sets. Amplicons were sequenced using the BigDye Terminator Cycle Sequencing Ready Reaction Kit in both directions according to the manufacturer's protocols. ResultsThe DNA sequence of A∗31:30 is identical to A∗31:01:02 in exons 2, 3, and 4, except for a nucleotide substitution at residue 539 (T→G) resulting in an amino acid replacement at position 156 (Leu→Trp). We deduced the probable HLA haplotype in association with A∗31:30 as A∗31:30-B∗15-DRB1∗14. The DNA sequence of B∗40:55 is identical to B∗40:01:01 in exons 2, 3, and 4 except for a nucleotide exchange at residue 814 (G→A) resulting in an amino acid substitution at position 248 (Val→Met). Two probable HLA haplotypes associated with B∗40:55 may be deduced as A∗02:07-B∗40:55-DRB1∗04:05 and A∗26:01-B∗40:55-DRB1∗09:01. ConclusionInformation about the deduced HLA haplotypes associated with the rare A∗31:30 and B∗40:55 alleles that we reported here is valuable for HLA tissue typing laboratories for reference purposes and for stem cell transplantation donor search coordinators to determine the likelihood of finding compatible donors in unrelated bone marrow donor registries for patients bearing these two uncommon HLA alleles. Because A∗31:30 and B∗40:55 have been found in Taiwanese population so far, we think the haplotypes that we reported here are most likely conserved in their population.

Discovery of a novel HLA-DRB1*04:05 variant, DRB1*04:05:15, in a Taiwanese and the probable HLA haplotype in association with DRB1*04:05:15

Here, we report a novel HLA-DRB1*04 allele, DRB1*04:05:15, found in a Taiwanese unrelated volunteer bone marrow hematopoietic stem cell donor by a sequence-based typing (SBT) method. The DNA sequence of DRB1*04:05:15 is identical to the sequence of DRB1*04:05:01 in exon 2, except the nucleotide at the position 198 where C is substituted by T (TAC→TAT at codon 37). Due to the silent mutation, the nucleotide replacement generated no amino acid variation in comparison with DRB1*04:05:01. We postulate the allele DRB1*04:05:15 was probably derived from DRB1*04:05:01 via a nucleotide point mutation event. The probable HLA-A, -B, -C, -DRB1 and -DQB1 haplotype in association with DRB1*04:05:15 may be deduced as A*02:01-B*48:01-C*08:03-DRB1*04:05:15-DQB1*04:01.

A conserved HLA‐A*02:28 associated HLA haplotype, A*02:28‐B*15:11‐DRB1*09:01, restricted to Taiwanese

HLA-A*02:28, found in a Korean and a Japanese, was reported independently to the IMGT/HLA database in 2003 and 2005, respectively. We report here eight Taiwanese unrelated bone marrow hematopoietic stem cell donors carrying A*02:28 detected during our routine HLA typing exercise. The probable HLA-A, -B and -DRB1 haplotype in association with A*02:28 may be deduced from the eight marrow stem cell donor as A*02:28-B*15:11-DRB1*09:01. Our result suggests A*02:28-B*15:11-DRB1*09:01 is a conserved HLA haplotype restricted to Taiwanese.

Recognition of a Caucasoid HLA‐B locus allele, B*44:55, in a Taiwanese/Chinese bone marrow stem cell donor

We detected a Caucasoid HLA-B allele, HLA-B*44:55, in a potential Taiwanese/Chinese bone marrow hematopoietic stem cell donor during our routine HLA SBT (sequence-based typing) practice. The sequence of B*44:55 varies with B*44:02:01:01 with one nucleotide in exon 2 at position 97 (T->C), while it differs from B*44:03:01 with one nucleotide in exon 2 at position 97 (T->C) and three nucleotides in exon 3 at residues 538-540 (CTG->GAC). The nucleotide replacements caused one amino acid variation with B*44:02:01:01 at residue 9 (Y->H) and two amino acid variations with B*44:03:01 at residue 9 (Y->H) and residue 156 (L->D). The formation of B*44:55 is probably the result of a nucleotide substitution involving B*44:02:01:01 at position 97 (T->C). The Taiwanese/Chinese donor with B*44:55 claims having no kinship with Caucasian. Our speculations on the origin of the Taiwanese/Chinese B*44:55 will be presented.