The relative frequencies of HLA-A*10 alleles in five major United States ethnic populations

The frequency of each A*10 allele was determined in 5 major United States ethnic populations randomly selected from a pool containing 82,979 unrelated individuals. The phenotype frequency of A10 was 10.5% in Caucasians, 14.0% in African-Americans, 21.1% in Asians/Pacific Islanders, 10.6% in Hispanics, and 9.8% in Native Americans. Fifty-nine individuals who had at least one A10 antigen were randomly chosen from each ethnic group for polymerase chain reaction using sequence-specific oligonucleotide probes (PCR-SSOP) typing. Thirteen of sixteen known A10 alleles were identified in this pool. The most common alleles observed were: A*2601 in Caucasians (55%), Hispanics (58%), and Native Americans (45%); A*3402 in African-Americans (34%); and A*3401 in Asians/Pacific Islanders (61%). The African-American and Asian/Pacific Islander populations differ from all other populations in the distribution of A*10 alleles, particularly, A*2601, A*3401, and A*3402.     

Frequencies of HLA-A2 alleles in five U.S. population groups. Predominance Of A*02011 and identification of HLA-A*0231

Direct DNA sequencing was used to determine the frequency of alleles within the HLA-A2 family in five US population groups. The most frequently detected HLA-A2 allele in all groups was HLA-A*02011. Caucasian and Native American populations appear to be the most homogeneous exhibiting 95.7% and 94.3% A*02011, respectively. Hispanic and Asian/Pacific Islander populations were the most allelicly diverse populations with 9 and 7 different HLA-A2 alleles present, respectively, but the majority of the populations were HLA-A*02011. African-Americans were also diverse, not in the number of alleles seen, but in the percentage of non-A*02011 alleles in the population. HLA-A*0202 (25.8%) and A*0205 (12.9%) were present in a large percentage of African-Americans. Only 13 of the 31 known HLA-A2 alleles were observed in the study. The allelic distributions reflected statistically significant differences among population groups.     

HLA-A*02 allele frequencies and haplotypic associations in Koreans

We have investigated the frequencies of HLA-A*02 alleles and their haplotypic associations with HLA-B and -DRB1 loci in 439 healthy unrelated Koreans, including 214 parents from 107 families. All of the 227 samples (51.7%) typed as A2 by serology were analyzed for A*02 alleles using polymerase chain reaction (PCR)-low ionic strength-single-strand conformation polymorphism (LIS-SSCP) method. A total of six different A*02 alleles were detected (A*02 allele frequency 29.6%): A*0201/9 (16.6%), *0203 (0.5%), *0206 (9.3%), *0207 (3.0%), and one each case of *0210 and *02 undetermined type. Two characteristic haplotypes showing the strongest linkage disequilibrium were A*0203-B38-DRB]*1502 and A*0207-B46-DRB1*0803. Besides these strong associations, significant two-locus associations (P<0.001) were observed for A*0201 with B61, DRB1*0901 and DRB1*1401, and for A*0206 with B48 and B61. HLA haplotypes carrying HLA-A2 showed a variable distribution of A*02 alleles, and all of the eight most common A2-B-DR haplotypes occurring at frequencies of > or =1% were variably associated with two different A*02 alleles. These results demonstrate that substantial heterogeneity is present in the distribution of HLA-A*02 alleles and related haplotypes in Koreans.     

The relationship between HLA-B45 and B* 5002 in the five major U.S. population groups

The antigen encoded by B*5002 differs in sequence from that encoded by B*5001 only at amino acid residue 167 (consensus tryptophan vs. serine) which results in B45 serologic reactivity. To search for B*5002, the frequencies of alleles encoding the serologically defined B45 antigen were determined by sequence-based typing in 5 major U.S. populations: Caucasians, African Americans, Asians/Pacific Islanders, Hispanics, and Native Americans. The percent of serologically defined B45-positive individuals in the 5 populations ranged from 0.7-9.0%. Thirty-two B45-positive individuals were randomly chosen, when available, for sequence-based typing from each ethnic group from a database of 82,979 consecutively typed unrelated individuals. The B*5002 allele was most prevalent in Hispanic (22%) and Caucasian (9%) individuals, while conspicuously absent in African Americans. In addition, a new allele associated with the B45 antigenic specificity, B*4502, has been identified from an African American individual of Middle Eastern descent. In light of the continuing need to reconcile differences between relationships determined by the sequence homologies among alleles and relationships based on the serologic determinants carried by allelic products when determining the level of HLA match for hematopoietic stem cell transplantation, it is suggested that B*5002 be recognized individually from other B*50 alleles when reporting HLA-B typings for clinical purposes.     

Development of PCR-SSOP for the identification of HLA-A*02 subtypes and determination of HLA-A*02 frequencies within different ethnic populations

A PCR-SSOP typing method, involving a single PCR amplification in conjunction with 19 digoxigenin labelled oligonucleotide probes, has been developed for the identification of 17 known HLA-A*02 alleles. The method has been applied to four populations (Northern Ireland, Singapore Chinese, Shetland Island and Mexican) and percentages of HLA-A*02 alleles determined within each population.     

HLA-A*2416: a new allele of the HLA-A19 lineage

We here report on a new HLA-A19 allele (A*2416) found in a German kidney recipient. Serological class I typing revealed HLA-A11,19 without clear definition of the A19 split antigen. As with serology, polymerase chain reaction (PCR)-based typing also revealed inconclusive results. We therefore sequenced the gene from the 5' flanking region through the 3'-end of exon 4 of this allele after haplotype-specific PCR amplification. The sequence analysis revealed a new HLA-A allele which is identical to A*3101 with the exception of the 3' half of exon 2 which is identical to the common A9 alleles. The phylogenetic analysis constructed with the nearest-neighbor algorithm and based on exons 1-4 or introns 1-3 clearly indicated, that A*2416 belongs unequivocally to the A19 lineage.     

HLA-A and HLA-B in Kenya,Africa: allele frequencies and identification of HLA-B*1567 and HLA-B*4426

HLA-A and HLA-B alleles of a population from Kenya, Africa were examined by sequencing exon 2 and exon 3 DNA and typing using a Taxonomy-based Sequence-analysis (TBSA) method. Extensive diversities were observed at both HLA-A and HLA-B loci in this population. Forty-one HLA-A alleles were identified from 159 unrelated individuals. The most frequently observed alleles were A*6802 (11.64%), A*02011/09 (9.75%), A*7401/02 (9.43%), A*3001 (7.86%), A*3002 (7.23%) and A*3601 (6.6%). Forty-nine HLA-B alleles were identified in 161 unrelated individuals, including two novel alleles, B*1567 and B*4426. The most frequently observed HLA-B alleles were B*5301 (9.01%), B*5801 (8.38%), B*4201 (7.76%), B*1503 (7.14%), B*1801 (6.21%), and B*5802 (5.90%). The most frequently observed HLA-A-B haplotypes were A*3601-B*5301 (3.55%) and A*3001-B*4201 (3.19%), followed by A*7401/02-B*5801 (2.84%), A*7401/02-B*5802 (2.84%) and A*02011/09-B*1503 (2.13%). Linkage disequilibrium and chi2 analysis showed the association of these HLA-A-B haplotypes at the antigen level to be significant. The frequencies of HLA-A and HLA-B alleles from the Kenyan population were compared with that of a population from Cameroon. The difference in allele and haplotype frequency distributions partly reflected the different ethnic composition of these two African populations.     

HLA-A, -B and -DRB1 allele frequencies in the Bangladeshi population

Population genetic studies have become an invaluable tool because of the extreme polymorphism found at some of the loci of the human leukocyte antigen (HLA) system. In this study, we are reporting for the first time the genetic polymorphism of 141 healthy unrelated Bangladeshi Bangalees living in central region of Dhaka. We studied the HLA-A, -B and -DRB1 loci using polymerase chain reaction with sequence-specific primers. The allelic frequencies, two and three locus haplotype frequencies were statistically analyzed. A total of 16 HLA-A alleles, 26 HLA-B alleles and 14 HLA-DRB1 alleles were detected. A*33-B*44 (8.15%) was the most common two loci class 1 haplotype, whereas A*33-B*44-DRB1*07 (6.38%) was the most frequent three loci haplotype. The most common HLA-A, HLA-B and HLA-DRB1 alleles were A*33 (17.02%), B*15 (19.5%) and DRB1*15 (29.07%), respectively. Construction of phylogenetic tree using average linkage between groups and correspondence analysis showed close associations with Indian non-tribal random Dravidians, north Indian Hindus and some relations with Mongolian and Pakistani populations. We believe this data will provide useful information for bone marrow registry, legal medicine, disease association and anthropological studies.     

Sequence analysis of the new allele HLA-A*020112

The novel allele HLA-A*020112 differs from HLA-A*020101 by a synonymous nucleotide exchange at position 53 in exon 2 (G-->A).     

HLA-A, -B and -DR allele and haplotype frequencies in Malays

One thousand four hundreds and forty-five Malays registered with the Malaysian Marrow Donor Registry were typed for HLA-A, HLA-B and HLA-DR. Fifteen HLA-A, twenty nine HLA-B and fourteen HLA-DR alleles were detected. The most common HLA-A alleles and their frequencies were HLA-A24 (0.35), HLA-A11 (0.21) and HLA-A2 (0.15). The most common HLA-B alleles were HLA-B15 (0.26), HLA-B35 (0.11) and HLA-B18 (0.10) while the most common HLA-DR alleles were HLA-DR15 (0.28), HLA-DR12 (0.27) and HLA-DR7 (0.10). A24-B15-DR12 (0.047), A24-B15-DR15 (0.03) and the A24-B35-DR12 (0.03) were the most frequent haplotypes. This data may be useful in determining the probability of finding a matched donor and for estimating the incidence of HLA associated diseases.     

Identification of a novel HLA-A allele HLA-A*2451 in a Chinese donor

A novel human leucocyte antigen-A (HLA-A) allele, A*2451, has been identified during routine sequence-specific oligonucleotide typing and sequence-based typing of a sample from a registered donor of the Chinese Marrow Donor Program. The A*2451 allele differs from the closest matching allele A*2415 by one nucleotide substitution in exon 3, nt 363 G-->A, resulting in an amino acid change from M ATG to I ATA at codon 121.     

Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations.

The HLA system is the most polymorphic of all human genetic systems. The frequency of HLA class I alleles and their linkage disequilibrium patterns differ significantly among human populations as shown in studies using serologic methods. Many DNA-defined alleles with identical serotypes may have variable frequencies in different populations. We typed HLA-A, B, and C loci at the allele level by PCR-based methods in 1,296 unrelated subjects from five major outbred groups living in the U.S.A (African, AFAM; Caucasians, CAU; Asian, ORI; Hispanic, HIS, and North American Natives, NAI). We detected 46, 100 and 32 HLA-A, B, and C alleles, respectively. ORI and HIS presented more alleles at each of these loci. There was lack of correlation between the levels of heterozygosity and the number of alleles detected in each population. In AFAM, heterozygosity (>90%) is maximized at all class I loci. HLA-A had the lowest heterozygosity in all populations but CAU. Tight LD was observed between HLA-B and C alleles. AFAM had weaker or nonexistent associations between alleles of HLA-A and B than other populations. Analysis of the genetic distances between these and other populations showed a close relationship between specific US populations and a population from their original continents. ORI exhibited the largest genetic distance with all the other U.S. groups and were closer to NAI. Evidence of admixture with CAU was observed for AFAM and HIS. HIS also had significant frequencies of AFAM and Mexican Indian alleles. Differences in both LD and heterozygosity levels suggest distinct evolutionary histories of the HLA loci in the geographical regions from where the U.S. populations originated.     

Haplotype-specific sequence-based typing shows the novel allele HLA-A*030105

The novel allele human leukocyte antigen (HLA)-A*030105 differs from HLA-A*030101 by a synonymous nucleotide exchange at codon 87 in exon 2 (G→A).     

Molecular and serological identification of the HLA-A*3404 allele

A novel HLA-A null allele, A*0253 N, has been identified in two generations of a Chinese family using combined serological and molecular cloning approaches. Full-length genomic DNA sequencing indicated that this new allele differs from HLA-A*02011 by a single C to G substitution at nucleotide position 324 in exon 2. This mutation results in an amino acid change from a tyrosine codon to a stop codon at position 108. A PCR-SSP based method was developed to distinguish A*0253 N from A*02 alleles. No further individuals of A*0253 N were found in 718 Chinese blood donors who carry the HLA-A*02 allele1.     

A new HLA-A allele, HLA-A*6824, identified in three unrelated individuals

A novel allele, human leukocyte antigen (HLA)-A*6824, has been identified in three unrelated individuals of northwestern European origin in a period of less than 4 months, implying that this allele may be quite common in this population. HLA-A*6824 differs from A*680102 by a single nucleotide change at position 275 in exon 2, which results in a conservative amino acid substitution from lysine to arginine in the peptide-binding groove at codon 68.     

Identification of a novel HLA-A allele, A*29:28, in an East African population

The new allele is identical to A*29:01:01:01 in exons 2 and 3, except for a single-nucleotide substitution (TTG to TGG) at codon 156.     

Distribution of HLA-A alleles in eight ethnic groups from Pakistan

The extreme polymorphism found at some loci of the HLA system has made it an invaluable tool for population genetic analyses. In this study eight diverse ethnic groups from Pakistan were analyzed at the HLA-A locus using sequence specific primers for polymerase chain reaction (PCR-SSP) and then further typed to the allele level using a two-stage sequence specific oligonucleotide probe (SSOP) strategy. Four of these ethnic groups (Burusho, Hazara, Kalash, Pathan) were from the north and four (Baloch, Brahui, Sindhi and Parsi) were from the south of Pakistan. Nine alleles were identified as unique to a particular ethnic group within Pakistan. Maximum variation was seen in the HLA-A*02 allele family for which 11 alleles were detected in the eight Pakistani ethnic groups. The alleles that showed significant variation between the Pakistani ethnic groups include A*0101, A*0206, A*0209, A*0207, A*0217, A*1101, A*2402/09 N/11 N, A*2902, A*3301 and A*3001. A phylogenetic tree based on DA distances for HLA-A allele frequencies separated the Pakistani populations from other world populations and also separated the only Dravidian speaking population of Pakistan, the Brahui, from the remaining Indo-European speaking ethnic groups of Pakistan.