Human leukocyte antigen allele and haplotype frequencies in Singapore bone marrow donors and cord blood units.

We describe the allele and haplotype frequencies seen in a volunteer unrelated bone marrow donor registry, a public cord blood bank, and donor/recipient samples processed by the Health Sciences Authority (HSA) in Singapore. Historical human leukocyte antigen (HLA) typing reports were anonymized and combined. They were checked for HLA typing nomenclature discrepancies or ambiguities using the HLA-net UNIFORMATE tool, and for analysis, the validated data were subsequently separated into Chinese, Malay, Indian, and "Others," according to the race classification system used in Singapore. Individual ethnic allele and haplotype frequencies were calculated with the HLA-net GENE[RATE] pipeline using basic statistics. The Basic Statistics Tool of HLA-net was used to estimate haplotype frequency using an expectation maximization algorithm, given a set of multi-allelic data pairs for a given HLA locus. The outputs downloaded from the site comprised plain text files with haplotype frequency estimates, results of a global linkage disequilibrium test, and standardized residuals (stdres) corresponding to deviations from expected frequencies. HLA typing results from 59,186 individuals met the inclusion criteria, yielding 118,372 analyzable alleles. In our study population, the haplotype A*33:03-B*58:01-C*03:02-DRB1*03:01～DQB1*02:01:01G with a frequency of 4.91% was the most common. This haplotype was also the most common among Singaporean Chinese donors. Consistent with the predominant Chinese population, haplotypes with a frequency greater than 1% were also the most frequently observed haplotypes in the Singaporean population. In the Malay donor population, the most common haplotype was A*33:03～B*44:03～C*07:01:01G～ DRB1*07:01-DQB1*02:01:01G, with a frequency of 3.41%, whereas within the Indian donor population, the most common haplotype was A*01:01-B*57:01-C*06:02～DRB1*07:01-DQB1*03:03, with a frequency of 3.42%. Haplotype diversity and composition statistics within donor pools provide HLA background data required for the targeted recruitment of donors to support the hematopoietic stem cell donor requirements of the country. These data may be used in the future to devise donor recruitment strategies for optimizing the donor pool through targeted publicity and accruals.

Detection of the HLA-B*15:404 allele in a Singaporean bone marrow donor.

Nucleotide substitutions in codons 67 and 119 of HLA-B*15:02:01:01 result in a novel allele, HLA-B*15:404.

Recognition of the HLA-DRB1*14:119 allele in a Singaporean bone marrow donor.

Nucleotide substitutions in exon 2 of DRB1*14:54:01:01 result in the novel DRB1*14:119 allele.

Recognition of the HLA-C*07:199:01 allele in a Singaporean unrelated hematopoietic stem cell donor.

One nucleotide substitution in codon 95 of HLA-C*07:04:01:01 results in a novel allele, HLA-C*07:199:01.

Recognition of the HLA-C*03:88 allele in a Singaporean bone marrow donor.

One nucleotide substitution in codon 108 of HLA-C*03:03:01:01 results in a novel allele, HLA-C*03:88.

Detection of the HLA-B*18:116 allele in a Singaporean bone marrow donor.

One nucleotide substitution in codon 120 of HLA-B*18:01:01:01 results in a novel allele, HLA-B*18:116.

Discovery of the novel HLA-C*06:195 allele in a Singaporean unrelated hematopoietic stem cell donor.

One nucleotide substitution in Codon 58 of HLA-C*06:02:01:01 results in a novel allele, HLA-C*06:195.

Identification of a novel HLA-A*01 variant, HLA-A*01:211, in a Singaporean Malay bone marrow donor.

One nucleotide substitution in codon 73 of HLA-A*01:01:01:01 results in a novel allele, HLA-A*01:211.

HLA-B*38:64, an HLA-B*38 variant, detected in a Singaporean Malay unrelated hematopoietic stem cell donor.

One nucleotide substitution in codon 89 of HLA-B*38:02:01:01 results in a novel allele, HLA-B*38:64.

HLA-DQB1*06:132, an HLA-DQB1*06 variant, discovered in a Singaporean Malay bone marrow donor.

One nucleotide substitution in codon 38 of HLA-DQB1*06:01:01:01 results in a novel allele, HLA-DQB1*06:132.

HLA-DQB1*05:66:01, a novel variant of HLA-DQB1*05, identified in a Singaporean Malay bone marrow donor.

Nucleotide substitutions in codon 38 of HLA-DQB1*05:03:01:01 result in a novel allele, HLA-DQB1*05:66:01.

HLA-DQB1*05:116, an HLA-DQB1*05 variant, detected in a Singaporean Chinese individual.

One nucleotide substitution in codon 87 of HLA-DQB1*05:02:01:01 results in a novel allele, HLA-DQB1*05:116.

Discovery of HLA-DPB1*454:01 in a Singaporean Malay individual.

One nucleotide substitution in codon 85 of HLA-DPB1*04:01:01:01 results in a novel allele, HLA-DPB1*454:01.

HLA-DPB1*526:01 detected in two Singaporean Indian individuals.

One nucleotide substitution in codon 84 of HLA-DPB1*02:01:02:01 results in a novel allele, HLA-DPB1*526:01.

HLA-B*15:349:02, a novel variant of HLA-B*15, discovered in a Singaporean Malay bone marrow donor.

One nucleotide substitution in codon 112 of HLA-B*15:349:01 results in a novel allele, HLA-B*15:349:02.

Discovery of HLA-B*35:368, a novel HLA-B*35 variant, in a Singaporean Malay hematopoietic stem cell donor.

DNA substitutions from codons 69 to 71 of HLA-B*35:05:01:01 result in a novel allele, HLA-B*35:368.

Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0.

A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well-documented (≥5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.

Detection of an HLA-A*02 variant, HLA-A*02:611, in a Singaporean Chinese individual.

One nucleotide replacement in codon 13 of HLA-A*02:01:01:01 results in a novel allele, HLA-A*02:611.

HLA-DQB1*05:115, an HLA-DQB1*05:01:01:01 variant, identified in a Singaporean Indian individual.

One nucleotide substitution in codon 46 of HLA-DQB1*05:01:01:01 results in a new allele, HLA-DQB1*05:115.

HLA-C*07:465, a novel HLA-C*07 variant, detected in a Singaporean Chinese individual.

One nucleotide replacement in codon 50 of HLA-C*07:02:01:01 results in a novel allele, HLA-C*07:465.