HLA Haplotype In Association Research Articles

Human leukocyte antigen-A*24:02-B*40:247-C*03:04-DRB1*16:02, a deduced probable human leukocyte antigen haplotype associated with a low-incidence human leukocyte antigen allele B*40:247 in Taiwanese individuals: A case analysis.

Objective:HLA-B*40:247 is a low incidence allele in the HLA-B locus. The aim of this study is to confirm the ethnicity of B*40:247 and its deduced probable HLA- associated haplotype in Taiwanese individuals.Materials and Methods:A total of 2,329 unrelated Taiwanese individuals and 66,212 unrelated mainland Chinese individuals were tested for HLA using a sequence-based typing method. We confirmed the low incidence allele B*40:247 in Taiwanese. Polymerase chain reaction was performed to amplify exons 2, 3 and 4 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.Results:The DNA sequence of B*40:247 is identical to B*40:01:01 in exons 2, 3 and 4 except for residue 853, where G of B*40:01:01 is changed to A in B*40:247 (codon 261, GTA->ATA). The nucleotide replacement causes a one amino acid change at codon 261 where V (valine) of B*40:01:01 is replaced by I (isoleucine) in B*40:247. We deduced the probable HLA haplotype associated with B*40:247 in Taiwanese to be HLA-A*24:02-B*40:247-C*03:04-DRB1*16:02.Conclusion:Information on the ethnicity and distribution of B*40:247 and its deduced probable HLA haplotype in association with the low incidence 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.

HLA haplotype in association with the low incidence C*07:66 allele found by case analysis of Taiwanese and mainland Chinese individuals

ObjectivesHLA-C*07:66 is a low-incidence HLA-C allele. The aim of the study is to report the Taiwanese and mainland Chinese ethnicities of individuals with C*07:66, together with its uniqueness and polymorphism. Materials and MethodsA sequence-based typing method was employed to confirm this low-incidence allele. Polymerase chain reaction was performed to amplify exons 2, 3, and 4 of the HLA-A, HLA-B, and HLA-C loci and exon 2 of the HLA-DRB1 and HLA-DQB1 loci using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kit. The blood donors in this study consisted of randomized Taiwanese and mainland Chinese individuals and family members with the C*07:66 allele. ResultsThe DNA sequence of C*07:66 is identical to that of C*07:02:01:01 for exons 2, 3, and 4, except for residue 688 in exon 4. This nucleotide substitution causes a single amino acid alteration to the protein sequence of C*07:02:01:01. Confirmation of the DNA and protein sequences of C*07:66 and the Taiwanese and mainland Chinese ethnicities of individuals with this allele were established in this study. One probable HLA C*07:66-associated HLA haplotype may be deduced from these individuals. ConclusionThe information on the ethnicity of the C*07:66 allele and the deduced probable HLA haplotype associated with the low-incidence C*07:66 allele reported in this study may aid in HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplant donor search coordinators to help create, for patients bearing this uncommon HLA allele, strategies for finding compatible donors using bone marrow donor registries comprising unrelated individuals.

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.

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.

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 novel HLA‐B allele, B*58:01:12, detected in a Taiwanese volunteer bone marrow stem cell donor using sequence‐based typing method

Human leukocyte antigen-B*58:01:12, a novel rare allele of HLA-B*58:01 variant, was found in a Taiwanese volunteer bone marrow donor by SBT (sequence-based typing) method. The DNA sequence of B*58:01:12 is identical to the sequence of B*58:01:01 in exons 2, 3 and 4 except at nucleotide position 483 where nucleotide C is substituted by T (at codon 137; GAC GAT). Due to the silent point mutation, the amino acid sequence of B*58:01:12 is identical to the sequence of B*58:01:01. The HLA haplotype in association with B*58:01:12 may be deduced as A*33:03-B*58:01:12-DRB1*03:01. The discovery of B*58:01:12 adds further polymorphism of B*58:01 in Taiwanese population.

Discovery of HLA‐DRB1*03:20 allele in a Taiwanese volunteer hematopoietic stem cell donor and the probable HLA‐A, ‐B, ‐C and ‐DRB1 haplotype in association with DRB1*03:20

The allele HLA-DRB1*03:20, a variant of DRB1*03, was first reported to the IMGT HLA database in April 2001 without indication on the ethnicity of the blood donor (Cell ID: HC 125775). We found a Taiwanese volunteer hematopoietic stem cell donor carries DRB1*03:20 by a sequence-based typing (SBT) method. The DNA sequence of DRB1*03:20 is identical to the sequence of DRB1*03:01:01 in exon 2, except a nucleotide substitution at position 341(T→C) (GTT→GCT at codon 85). The nucleotide replacement produced an amino acid variation at residue 85 (V→A). We hypothesize that DRB1*03:20 was probably derived from DRB1*03:01:01 via a nucleotide point mutation event. The probable HLA haplotype in association with DRB1*03:20 was deduced as A*11:02-B*58:01-C*07:02-DRB1*03:20. We here report the Taiwanese/Chinese ethnicity of DRB1*03:20.

Recognition of HLA‐A*24:137 allele in a Taiwanese unrelated bone marrow stem cell donor and the plausible HLA haplotype associated with A*24:137

We detected a rare HLA-A*24:137 allele in an unrelated Taiwanese haematopoietic stem cell donor during a routine SBT (sequence-based typing) HLA typing exercise. The DNA sequence of A*24:137 is identical to the sequence of A*24:02:01:01 in exons 2 and 3 except at codon 21 where CGC was replaced with CAA. The DNA variation caused an amino acid alteration at amino acid residue 21 (R->Q). The HLA haplotype in association with A*24:137 may be deduced as A*24:137-B*15-DRB1*14. The formation of A*24:137 was probably the result of a nucleotide point mutation involving A*24:02:01:01. It remains to be determined whether A*24:137 is restricted to Taiwanese/Chinese ethnicity.

Discovery of a novel HLA‐B*51 variant, B*51:112, in a Taiwanese bone marrow donor and identification of the plausible HLA haplotype in association with B*51:112

The sequence of B*51:112 is identical to the sequence of B*51:01:01 in exons 2, 3 and 4, except the nucleotides at positions 206 (C→A) and 213 (C→G). The nucleotide replacement caused one amino acid substitution at residue 45 (T→K). The plausible HLA-A, -B and -DRB1 haplotype in association with B*51:112 may be deduced as HLA-A*02-B*51:112-DRB1*12. The generation of B*51:112 was probably as the result of a DNA recombination event where B*40:01:01 acted as a sequence donor donating a segment of the DNA sequence to the recipient sequence B*51:01:01. The donor carrying B*51:112 was a Minna Taiwanese whose ancestor came to Taiwan from the southern region of China.

Oriental HLA‐A*11:90 detected in a Taiwanese cord blood sample and the haplotype in association with A*11:90 allele

We report here an HLA-A allele, A*11:90, found in a Taiwanese cord blood sample using DNA sequence-based typing (SBT) protocol after observing an anomalous reaction pattern in a sequence-specific oligonucleotide (SSO) typing exercise. The sequence of A*11:90 is identical to A*11:01:01, the most predominant A*11 variant in Taiwanese, in exon 2 but differs from A*11:01:01 in exon 3 by two nucleotide substitutions at codon 163 (c.487C>G and c.488G>A), resulting R163E. In comparison with the sequence of A*11:02:01, the second most predominant subtype of A*11 in Taiwanese A*11:90 has one nucleotide difference at codon 19 (c.55A>G) in exon 2 resulting K19E and two nucleotides variations at codon 163 (c.487C>G and c.488G>A) in exon 3 resulting R163E. HLA-A*11:90-B*40:02-DRB1*11:01 is the deduced probable HLA haplotype in association with A*11:90. The generation of A*11:90 is thought to involve a DNA recombination event between alleles A*11:01:01 and A*80:01 where A*80:01 donated a fragment of the DNA sequence (from n.t. 487 to n.t. 497) to the recipient sequence of A*11:01:01.

Unfavorable prognosis of patients with non-small cell lung carcinoma associated with HLA-A2

Background: HLA class I molecules present antigenic peptides to cytotoxic T lymphocytes and, thus, play an important role in immune surveillance. Since 1970s there have been many reports of an increased frequency of one or more HLA haplotype in association with autoimmune disease, and malignancy. We studied types of HLA class I antigens in 204 resected non-small cell lung carcinoma (NSCLC) patients and also examined its correlation with clinicopathologic features and prognosis. Method: serological typing for HLA class I antigens was performed using a microcytotoxicity test. The disease-free survival curves were calculated by the Kaplan-Meier method and then compared using the Logrank test. Multivariate analysis was carried out by Cox's proportional hazard method. Results: the difference in disease-free survival time between the HLA-A2 present group and A2 absent group was significant ( P=0.040). The 3-year disease-free survival rate of all patients was 44% in HLA-A2 present group and 66% in A2 absent group. When a comparison was made within the group with stage I, expression of HLA-A2 was the only independent factor that affected survival time by multivariate analysis ( P=0.0457). Conclusions: expression of HLA-A2 was considered as one of the unfavorable prognostic factors in NSCLC patients. Our results suggested expression of HLA-A2 in NSCLC patients was one of the mechanisms of escape from immune surveillance.