HLA antigen and gene frequencies in Eskimos of East Greenland.

A population of 78 Ammassallik Eskimos was tested for HLA-A, B, Cw, DR and DQ specificities using serological techniques and HLA-Cw, DRB, DQB1 and DPB1 using three different genomic techniques. The application of two new genomic techniques for HLA-Cw (PCR-SSP phototyping) and HLA-DPB1 (PCR-RLFP) typing confirmed serological results and gave a higher resolution, with more heterozygotes than previously found. High gene frequencies of HLA-A24 (0.80), B51 (0. 21), B61 (0.30), B62 (0.21), Cw*0303 (0.27), Cw*0304 (0.51), DRB1*0401 (0.45), DRB1*1402 (0.24), DQ7 (0.88), DPB1*0201 (0.18), DPB1*0401 (0.40) and DPB1*0402 (0.30) were found. A limited number of alleles were found at all HLA loci. The Ammassallik Eskimos of East Greenland are genetically homogenous with little, if any, admixture with European populations. This contrasts with other Greenlandic populations formerly tested. The pattern of alleles indicates a close genetic relationship with other Eskimo populations.     

Identification of a novel DPB1* allele (DPB1*6901) and the occurrence of HLA haplotypes that extend to DPB1

The sequence of a novel DPB1 allele, DPB1*6901, observed in a Caucasian bone marrow donor phenotype HLA A2; Cw*0501,*1601; B*4402, *4403; DRB1*0401; *07; DQB1*02; *0301; DPB1*0401; *6901, is described. The sequence is consistent with that previously described for DPB1*0601 with the exception of codon 69. The sequence at this codon is consistent with that previously observed only in the DPB1*1101 and *1501 alleles. It is suggested that DPB1*6901 may have arisen as a result of a recombination event occurring between codons 58 and 64 between DPB1*0601 and DPB1*1101. The sequence of DPB1*1501 from codon 64 is not consistent with DPB1*6901. A linkage disequilibria analysis that examined 212 potential bone marrow recipients in which HLA-A to DQ haplotypes had been established by family studies showed linkage disequilibrium between HLA-B, DRB1 and DPB1 in some haplotypes and not others.     

中国湖北汉族HLA—Ⅱ类等痊基因频率的群体调查

调查中国湖北汉族人群ＨＬＡ－Ⅱ类基因频率。方法,用聚合酶链反应／序列特异性引物和聚合酶链反应／限制性片段长度多态性技术,对中国湖北汉族１６８名正常个体进行了ＨＬＡ－ＤＲＢ１（ｎ＝１６８）、ＨＬＡ－ＤＱＢ１（ｎ＝１６０）、ＨＬＡ－ＤＰＢ１（ｎ＝９３）基因的多态性检测。结果共检出３９种ＤＲＢ１、１５种ＤＱＢ１和１７种ＤＰＢ１等位基因型别,等位基因频率较高的分别是：ＤＲＢ１＊０９０１（ｇｅｎｅｆｒｅｑｕ     

Analysis of high‐resolution HLA‐A, ‐B, ‐Cw, ‐DRB1, and ‐DQB1 alleles and haplotypes in 718 Chinese marrow donors based on donor–recipient confirmatory typings

High‐resolution human leucocyte antigen (HLA)‐A, ‐B, ‐Cw, ‐DRB1, and ‐DQB1 alleles and haplotype frequencies were analysed from 718 Chinese healthy donors selected from the Chinese Marrow Donor Program registry based on HLA donor–recipient confirmatory typings. A total of 28 HLA‐A, 61 HLA‐B, 30 HLA‐Cw, 40 HLA‐DRB1 and 18 HLA‐DQB1 alleles were identified, and HLA‐A*1101, A*2402, A*0201, B*4001, Cw*0702, Cw*0102, Cw*0304, DRB1*0901, DRB1*1501, DQB1*0301, DQB1*0303 and DQB1*0601 were found with frequencies higher than 10% in this study population. Multiple‐locus haplotype analysis by the maximum‐likelihood method revealed 45 A–B, 38 Cw–B, 47 B–DRB1, 29 DRB1–DQB1, 24 A–B–DRB1, 38 A–Cw–B, 23 A–Cw–B–DRB1, 33 Cw–B–DRB1–DQB1 and 22 A–Cw–B–DRB1–DQB1 haplotypes with frequencies >0.5%. The most common two‐, three‐, four‐ and five‐locus haplotypes in this population were: A*0207–B*4601 (7.34%), Cw*0102–B*4601 (8.71%), B*1302–DRB1*0701 (6.19%), DRB1*0901–DQB1*0303 (14.27%), A*3001–B*1302–DRB1*0701 (5.36%), A*0207–Cw*0102–B*4601 (7.06%), A*3001–Cw*0602–B*1302–DRB1*0701 (5.36%), Cw*0602–B*1302–DRB1*0701–DQB1*0202 (6.12%) and A*3001–Cw*0602–B*1302–DRB1*0701–DQB1*0202 (5.29%). Presentation of the high‐resolution alleles and haplotypes data at HLA‐A, ‐B, ‐Cw, ‐DRB1 and ‐DQB1 loci will be useful for HLA matching in transplantation as well as for other medical and anthropological applications in the Chinese population.     

HLA antigens,alleles and haplotypes among the Yup'ik Alaska natives: report of the ASHI Minority Workshops,Part II

As part of the American Society for Histocompatibility and Immunogenetics coordinated studies among minority populations, human leukocyte antigen (HLA) alleles were defined for 460 volunteer Yup'ik Eskimos from the Yukon Kuskokwim delta region of southwestern Alaska. The study group included 252 adults with no other first-degree relatives and 48 informative nuclear families. Full Yupik ancestry through both maternal and paternal grandparents was claimed by 81.1% of participants. HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles were determined by SBT, SSOP, reverse SSOP, and/or RSCA according to the protocols of five participating laboratories. Polymorphism was limited with 3-6 alleles comprising > 80% of the alleles observed at each locus. Homozygosity was high, particularly at the HLA-A and -DQB1 loci, with 36.6% and 44% of individuals having a single allele defined at these respective loci. HLA-A, -B, and -DRB1 alleles were in Hardy-Weinberg equilibrium, whereas HLA-Cw and -DQB1 alleles gave significant deviation (p = 0.002; 0.005). Significant linkage disequilibrium (p < or = 0.00001) was observed in all pairwise evaluations. A new Cw*0806 allele was observed in high linkage disequilibrium with B*4801(Delta = 0.099; Delta(rel) = 1.0). Three extended haplotypes were found to have frequencies > 5%, the most prevalent being A*2402; B*4801; DRB1*0401; DQB1*0301 (0.0933). Comparison of available class I data indicate that the Yup'ik share several common alleles with other Native American populations, including: A*2402, *0206, *6801; B*1501, *2705, *3501, *4002, *4801, *5101; and Cw*0202, *0304, *0401. Comparisons of class II data also confirm a close relationship of the Yup'ik to two other Eskimo populations, Siberian and East Greenland Eskimos. DRB1*0401 and *1101, which occur in high frequency among these Eskimo populations, but not in other Native Americans, were also prevalent among the Yup'ik, with respective frequencies of 0.232 and 0.107.     

HLA allele and haplotype frequencies in the Albanian population and their relationship with the other European populations

Human leucocyte antigen (HLA) alleles are very interesting markers in identifying population relationships. Moreover, their frequency distribution data are important in the implementation of donor–recipient registry programs for transplantation purposes and also in determining the genetic predisposition for many diseases. For these reasons, we studied the HLA class I and II allele and haplotype frequencies in 160 healthy, unrelated Albanian individuals originating from all regions of the country. The HLA genotyping was performed through a 2‐digit resolution SSOP method. The data were analysed with Arlequin and Phylip programs. No deviation was found from the Hardy–Weinberg equilibrium. A total of 17 A*, 30 B*, 12 Cw*, 13 DRB1* and 5 DQB1* alleles were identified. The six most frequent HLA‐A‐B‐DRB1 haplotypes were A*02–B*18–DRB1*11 (5.60%), A*02–B*51–DRB1*16 (4.74%), A*01–B*08–DRB1*03 (3.48%), A*24–B*35–DRB1*11 (2.77%), A*02–B*51–DRB1*13 (2.21%), A*24–B*35–DRB1*14 (1.89%). Interestingly, 12 HLA‐A‐B‐Cw‐DRB1‐DQB1 haplotypes occurred at a frequency >1%. When compared with the other populations, a close relationship was found with North Greek, Bulgarian, Macedonian, Romanian, Turkish, Cretan, Serbian, Croatian and Italian populations. A higher differentiation in allele frequency level was found with Western Europe populations. These data are the first report of HLA allele and haplotype distribution in an Albanian population inside this country. When compared with other populations, their distribution frequencies show close similarities with neighbouring populations of the entire Balkan area.     

中国汉族人群供-受者HLA-A、B、Cw、DRB1和DQB1高分辨等位基因频率分布及错配比例的研究

目的 从基因高分辨水平,分析中国汉族人群供-受者人类白细胞抗原(human leukocyte antigens,HLA)-A、B、Cw、DRB1、DQB1各位点等位基因频率和分布的多态性;及供-受者等位基因匹配情况.方法 采用基因测序分型(sequence based typing,SBT)、序列特异性寡核苷酸探针法(sequence specific oligonueleotide probe,SSOP)和序列特异性引物法(sequence specific primer,SSP),对2540名中国汉族人的(其中1168名受者,1372名供者)DNA标本进行HLA高分辨基因分型,并作统计学处理.结果 2540份样本中共检测到44种HLA-A等位基因,频率高于0.05的A*1101、A*2402、A*0201、A*0207、A*3303、A*0206、A*3001共占80.4%;81种HLA-B等位基因,频率高于0.05的B*4001、B*4601、B*5801、B*1302、B*5101共占43.0%;44种HLA-Cw等位基因,频率高于0.05的Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0602、Cw*0303、Cw*0302、Cw*0401共占80.3%;61种HLA-DRB1等位基因,频率高于0.05的DRB1*0901、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*0701、DRB1*0405、DRB1*0301、DRB1*1101共占70.1%;22种HLA-DQB1等位基因,频率高于0.05的DQB1*0301、DQB1*0303、DQB1*0601、DQB1*0602、DQB1*0202、DQB1*0302、DQB1*0401、DQB1*0502、DQB1*0201共占87.4%.这5个位点均处于杂合子缺失状态,其中A、B、DRB1位点符合HardyWeinberg平衡(Hardy-Weinberg equi1ibrium,HWE)(P＞0.05);Cw、DQB1位点偏离HWE(P＜0.05);排除个别基因型观察值与期望值偏差较大外,这5个位点均符合HWE.在供-受者数据的比较中,HLA全相合(10/10)的比例仅22.4%;单个等位基因错配(9/10)的比例为24.6%;两个等位基因错配(8/10)的比例为26.3%.结论 中国汉族人群高分辨水平HLA-A、B、Cw、DRB1,DQB1等位基因频率及分布特点,对非亲缘造血干细胞移植供者检索有重要参考价值;并为中华骨髓库数据入库和利用提供遗传学依据.

Abstract：

Objective To analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients. Methods HLA highresolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out. Results Forty-four HLA-A alleles were detected, and among them the frequencies of A * 1101, A * 2402, A * 0201, A * 0207, A * 3303, A *0206 and A * 3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and frequencies of B * 4001, B * 4601, B * 5801, B * 1302 and B * 5101 exceeded 0. 05, and accounted for 43. 0% of total. There were 44 HLA- Cw alleles, among them the frequencies of Cw * 0702, Cw * 0102,Cw * 0304, Cw * 0801, Cw * 0602, Cw * 0303, Cw * 0302 and Cw * 0401 exceeded 0.05, and were 80.3 %of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1 * 0901, DRB1 * 1501, DRB1 * 1202,DRB1 * 0803, DRB1 * 0701, DRB1 * 0405, DRB1 * 0301 and DRB1 * 1101 exceeded 0. 05, and were 70. 1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1 * 0301, DQB1 *0303, DQB1 * 0601, DQB1 * 0602, DQB1 * 0202, DQB1 * 0302, DQB1 * 0401, DQB1 * 0502 and DQB1 *0201 exceeded 0. 05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P＞0. 05); but HLA-Cw and HLA-DQB1 loci did not (P＜0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24. 6% of recipients found single HLA allele mismatched donors (9/10); 26. 3% of recipients had two HLA alleles mismatched donors (8/10). Conclusion The characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.     

HLA-DP antigen and Takayasu arteritis

Sixty-four patients with Takayasu arteritis and 317 healthy individuals in the Japanese population were examined for HLA-A, -B and -C alleles by serological typing and for HLA-DR, DQ and DP alleles by DNA typing using PCR/SSOP analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601 and DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the combination or haplotype of HLA-Bw52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 -DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another combination or haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. Because this is the first evidence for the association between an HLA-DP allele and Takayasu arteritis, we examined the nucleotide sequences of the DPB1*0901 allele from a patient and her healthy relatives and found no difference. The disease is therefore not caused by a mutated DPB1 gene.     

Characteristics of HLA class I and class II polymorphisms in Rwandan women

OBJECTIVE: To define HLA class I and class II polymorphisms in Rwandans. METHODS: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. RESULTS: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were >/=0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. DISCUSSION: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.     

HLA-A, -B, -C, -DR, -DQ typing in a population group of Senegal: distribution of HLA antigens and HLA-DRB1*13 and DRB1*11 subtyping by PCR using sequence-specific primers (PCR-SSP)

One-hundred-and sixteen Senegalese Serere were typed for HLA antigens and compared with other ethnic groups in Gambia. We did not find significant differences (Fisher's exact test; P0.01) in the HLA antigens distribution between the Serere and Mandinka groups in Senegal and the Serere, Mandinka and Wolof in The Gambia. The most common HLA haplotypes found (P0.01; Chi square with Yates' correction) were: A1, B8; A2, B51; A32, B44; A33, B58; A2, Cw2; A2, Cw4; A33, Cw3; A2, DR17; A10, DR10; B35, Cw4; B53, Cw6; B57, Cw3; B65, Cw8; B50, DR15; B52, DR4; Cw2, DR17; DR7, DQ2; DR18, DQ4. The HLA-DRB1*13 and DRB1*11 alleles were subtyped by PCR-SSP and the frequencies of these alleles in the studied population given. HLA-DRB1*1304 and DRB1102 were the most common alleles found respectively 15.0 and 18.5%     

HLA‐DQ and DRB1 polymorphism and susceptibility to type 1 diabetes in Jamaica

Genetic susceptibility to type 1 diabetes is determined by a combination of HLA‐DQ and DRB1 alleles. In the present study, HLA associations with type 1 diabetes were investigated in the Jamaican population. DRB1 and DQ genotyping was performed on 45 type 1 diabetic patients and 132 control subjects born and resident in Jamaica. The small number of patients available for study reflected the low prevalence of type 1 diabetes in Jamaica. The results were compared with those from other African heritage populations and white Caucasians. The highest relative risk was associated with the DRB1*03‐DQ2/DRB1*04‐DQ8 genotype. Both DRB1*0401‐DQ8 and DRB1*0408‐DQ8 were positively associated with disease. DRB1*0408‐DQ8 is uncommon amongst white Caucasians, where DRB1*0401‐DQ8 is the major predisposing haplotype. The DRB1*1503‐DQ6 haplotype was associated with protection from diabetes in the Jamaican population. This haplotype is rare amongst white Caucasians, where DRB1*1501‐DQ6 is the protective haplotype. Data from African heritage populations suggest that DRB1*1503‐DQ6 might be less protective than DRB1*1501‐DQ6. DRB1*03‐DQA1*0401‐DQB1*0402 was associated with protection from diabetes in the Jamaican population, whereas in white Caucasians DRB1*08‐DQA1*0401‐DQB1*0402 is predisposing. These data demonstrate that comparison of genetic associations with type 1 diabetes in races with population‐specific DRB1‐DQ haplotypes provides new information as to the exact determinants of disease susceptibility. Further support is provided for roles of the DQ genes and the DRB1 gene (or a gene in linkage disequilibrium with it) in determining susceptibility to type 1 diabetes.     

Nucleotide sequence of the corrected DQB1*06011 allele

The DQB1*06011 allele first classified and registered with the codon ACC at position 51(1) was recently corrected to ACG by Dr. Akinori Kimura (2) and in independently confirmed in our laboratory (3). The correct nucleotide sequence for this allele is shown below. The DQB1*06011 allele was found in two sisters of Turkish nationality who had been serologically typed for class I as HLA-A11, A33, B44, B52, Cw4. Nucleotide sequencing based typing of HLA class II alleles disclosed DRB1*0701, *15021, DRB4*01011/*0103, DRB5*0102, DQA1*0103, *0201, DQB1*02, *06011, DPB1*0401,*11011.     

HLA class II alleles associated with celiac disease susceptibility in a Southern European population

Susceptibility to celiac disease in Northern Europe is associated with the human leukocyte antigens (HLA) B8, DR3 and DQ2, which exist together on an extended haplotype. The strong predominance of this haplotype within the Northern European celiac populations, together with the linkage disequilibrium which occurs between these loci, does not allow identification of the gene(s) primarily associated with disease susceptibility. Studies from Southern Europe using both serology and examination of restriction fragment length polymorphisms (RFLP) have demonstrated associations with DR3, DR7 and DQ2, suggesting that the DQ locus is primarily involved. We investigated 43 celiac patients and 41 healthy controls from Rome, Italy, using sequence-specific oligonucleotide (SSO) probes, in conjunction with gene amplification by the polymerase chain reaction (PCR), to determine alleles at the DRB, DQA1, DQB1 and DPB1 loci: 19% of celiac patients possessed the alleles DRB1*0301 DRB3*0101, 33% DRB1*0301 DRB3*0201 and 33% of celiac patients were heterozygous for DRB1*1101-1201/DRB1*0701. The strongest association with celiac disease susceptibility was the combination of alleles DQA1*0501 DQB1*0201 (91% celiac patients vs. 12% controls; p = 0.000002). There was no additional susceptibility associated with alleles at the DPB locus. This study confirms the hypothesis that susceptibility is associated with a particular combination of DQ alleles and the ethnic variation in DR frequencies is secondary to linkage disequilibrium with these DQ alleles.     

HLA class II DRB1, DQB1, DPB1 polymorphism and cardiomyopathy due to Trypanosoma cruzi chronic infection

Trypanosomiasis is an important cause of cardiomyopathy in endemic rural areas of Latin America. Previous studies have suggested participation of HLA molecules in the immune response regulation of T. cruzi infection, and association of HLA antigens with heart damage.One hundred and eleven unrelated T. cruzi antigen-seropositive individuals were tested for HLA class II alleles by the polymerase chain reaction and sequence specific oligonucleotide (PCR-SSO) method. Patients were classified in 3 groups according to clinical and electrocardiographic characteristics: asymptomatics (group A), with arrhythmia (group B), and with overt congestive heart failure (group C). Statistical analysis confirmed the significant increment of the DRB1*01 DQB1*0501 haplotype (p = 0.03) previously reported by our laboratory in patients with cardiomyopathy. The DPB1*0401 allele frequency is also significantly increased in patients with heart disease (groups B + C) (p = 0.009) while DPB1*0101 frequency is higher among the asymptomatic group (p = 0.04) compared with individuals of group C. The DPB1*0401 allele in homozygous form or in combination with allele DPB1*2301 or 3901, was found present more often in patients of groups B and C. Thus, the combination of two of these three alleles, sharing specific sequence motifs in positions 8, 9, 76, and 84-87 confers a relative risk of 6.55 to develop cardiomyopathy in seropositive patients (p = 0.041). Furthermore, 32% of the cardiomyopathics have either DRB1*01 DQB1*0501 and/or DPB1*0401/*0401, 0401/*2301, or* 0401/*3901 compared with 9% of the seropositive asymptomatics (OR = 5.0; p = 0.006).     

HLA polymorphism in a Mataco South American Indian tribe: Serology of class I and II antigens: Molecular analysis of class II polymorphic variants

In the present study, HLA-A, B, C, DR, DQ, and DP loci were analyzed in a group of Mataco Amerindians of Argentina. Using reagents from the 11th International Histocompatibility Workshop (11th IHW), class I specifities such as Bw70, Bw75, and Bw48 were found in this population, other than the HLA determinants commonly described in South American Indians. The class II antigens found were DR4, DRw14, and DRw8 at the DR locus, and DQw4 and DQw7 at the DQ locus. The analysis of DRB1-DR4 related alleles, performed by PCR amplification and oligonucleotide probe hybridization, showed the presence of DRB1*0403, *0404, *0405, and *0411 in individuals from this ethnic group. By the analysis of DRB1-DRw14 related alleles, two variants were found: DRB1*1402 and DRB1*1406, the latter provisionally called DRB1 14.6 in 11th IHW. The DRw8-related allele present was DRB1*0802. The analysis of DRB3 gene revealed only the presence of DRB3*0101 allele in DRw14 individuals. DPB1 locus was also analyzed in unrelated individuals of the same population. Only five DPB1 alleles were found: DPB1*0201, *0301, *0402, *0501, and *1301 over the 19 previously described in the literature. These findings emphasize the restricted HLA class I and II variation observed in this ethnic group as it has been previously shown in other American groups. Some particular haplotypes in this Mataco tribe are described in this work.     

HLA alleles and haplotypes in French North African immigrants

Human leukocyte antigen (HLA) haplotypes (n = 187) were genotyped and assigned by the mode of inheritance in migrant families from North Africa who reside in the Paris, France, area. The distribution of alleles and haplotypes in that population was compared with the one obtained in a control population of ancient French natives residing in the same area (248 independent haplotypes also assigned by the mode of inheritance were studied). The results in migrants reveal the following: (1) a higher diversity in the distribution of HLA-A and -DRB1 alleles; (2) lower frequencies of alleles common in our region, such as A*0201 B*1501, B*4001, and DRB1*0401 and increased frequencies of minor subtypes, such as A*3002 and DRB1*0402; and (3) distinct distributions of B/Cw, DRB1/DQB1 or B/Cw/DRB1/DQB1 haplotypes. The results also revealed that the four most frequent five-allele haplotypes in controls i.e., HLA-A*0101/B*0801/Cw*0701/DRB1*0301/DQB1*0201; A*0301/B*0702/Cw*0702/DRB1*1501/DQB1*0602 (both of Indo-Celtic origin); A*2902/B*4403/Cw*1601/DRB1*0701/DQB1*0202 (frequent in Western-Europeans); and A*0201/B*1501/Cw*0304/DRB1*0401/DQB1*0302, represent 10.5% of the total haplotypes in controls but 1.6% in North Africans. Conversely, 9 five-allele haplotypes in multiple copy in North Africans (among which A*3002/B*1801/Cw*0501/DRB1*0301/DQB1*0201 of Paleo-North African origin and A*0201/B*0702/Cw*0702/DRB1*1501/DQB1*0602 of ancient European and Paleo-North African origin) represent 9.6% of the total haplotypes in North Africans but 2.4% in controls. These results thus suggest a low degree of admixture between the two populations.     

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish caucasian populations

Ulcerative colitis (UC) and Crohn's disease (CD) are the clinical entities comprising idiopathic inflammatory bowel disease (IBD). Previous studies on the association of IBD and human leukocyte antigen (HLA) class II genes suggested a role for HLA in this disease. Here we present HLA class II (DRB1, DQB1, DQA1, DPB1) allele and haplotype distributions determined using the polymerase chain reaction and sequence-specific oligonucleotide probe methods. A total of 578 UC and CD Caucasian patients and controls from Jewish (Ashkenazi) and non-Jewish populations was examined. Our previously reported association of DR1-DQ5 with CD was attributable to DRB1*0103. A dramatic association with IBD and the highly unusual DRB1*0103-DQA1*0501-DQB1*0301 haplotype (OR = 6.6, p = 0.036) was found. The more common DR1 haplotype, DRB1*0103-DQA1*0101-DQB1*0501, was also associated with IBD (OR = 3.1, p = 0.014), a result suggesting that interaction between DR and DQ may determine the extent of disease risk. Our previously reported association of DR2 with UC was attributable to DRB1*1502 (OR = 2.6, p = 0.006). At the DPB1 locus, a significant association of DPB1*0401 with CD was observed for the combined populations (OR = 1.85, p = 0.007). These observations indicate that some class II alleles and haplotypes confer susceptibility to both UC and CD, implying common immunogenetic mechanisms of pathogenesis, while others confer risk to only one of these diseases, and illustrate the value of DNA HLA typing in disease susceptibility analyses.     

MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data

In the present study, DNA typing for HLA-A, C, B, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, and DPB1 was performed for 246 healthy, unrelated Greek volunteers of 20-59 years of age. Phenotype, genotype frequencies, Hardy-Weinberg equilibrium fit, and 3-locus haplotype frequencies for HLA-A, C, B, HLA-A, B, DRB1, HLA-DRB1, DQA1, DQB1, and HLA-DRB1, DQB1, DPB1 were calculated. Furthermore, linkage disequilibrium, deltas, relative deltas and p-values for significance of the deltas were defined. The population studied is in Hardy-Weinberg equilibrium, and many MHC haplotypes are in linkage disequilibrium. The most frequent specificities were HLA-A*02 (phenotype frequency = 44.3%) followed by HLA-A*24 (27.2%), HLA-B*51 (28.5%), HLA-B*18 (26.8%) and HLA-B*35 (26.4%) and HLA-Cw*04 (30.1%) and HLA-Cw*12 (26.8%). The most frequent MHC class II alleles were HLA-DRB1*1104 (34.1%), HLA-DQB1*0301 (54.5%) and HLA-DPB1*0401 with a phenotype frequency of 59.8%. The most prominent HLA-A, C, B haplotypes were HLA-A*24, Cw*04, B*35, and HLA-A*02, Cw*04, B*35, each of them observed in 21/246 individuals. The most frequent HLA-A, B, DRB1 haplotype was HLA-A*02, B*18, DRB1*1104 seen in 20/246 individuals, while the haplotype HLA-DRB1*1104, DQB1*0301, DPB1*0401 was found in 49/246 individuals. Finally, the haplotype DRB1*1104, DQA1*0501, DQB1*0301 was observed in 83/246 individuals. These results can be used for the estimation of the probability of finding a suitable haplotypically identical related or unrelated stem cell donor for patients of Greek ancestry. In addition, they can be used for HLA and disease association studies, genetic distance studies in the Balkan and Mediterranean area, paternity cases, and matching probability calculations for the optimal allocation of kidneys in Greece.     

HLA‐DPB1*0401 is associated with dominant protection against type 1 diabetes in the general Saudi population and in subjects with a high‐risk DR/DQ haplotype

The human leukocyte antigen (HLA) class II DQB1*0201/0202‐DRB1*04 genotype has been identified as predisposing to type 1 diabetes [insulin‐dependent diabetes mellitus (IDDM)] in the Saudi Arabian population (P = 0.0002; odds ratio = 0.67; 95% confidence interval = 0.009–0.381). In this study, we searched for a factor at the DPB1 locus by analysing DPB1 polymorphism using sequence‐based typing in 86 Saudi IDDM patients and control subjects, all carrying the HLA‐DRB1*04/DQB1*02 haplotype or the known susceptibility allele DQB1*0201/0202. Significant protection was conferred by DPB1*0401, which was observed in 17 of 50 control subjects (55%) and 2 of 36 IDDM patients (5%) with the DQB1*0201/0202 allele (P = 0.0012; odds ratio = 8.75; confidence interval = 1.72–59.70). Our data showing a high frequency of the DPB1*0401 allele even in the presence of the predisposing DQB1*02 allele in healthy subjects may indicate a protective effect of this combination of HLA alleles against type 1 diabetes. This finding supports the hypothesis that protective HLA class II genes can override the risk conferred by HLA‐DQ susceptibility alleles. Further studies using larger cohorts of control subjects and patients should be undertaken to confirm this observation.     

Immunogenetics of the rare HLA‐B allele B*4408†

The nucleotide sequence of exons 2 and 3 of B*4408 has been confirmed. This allele has now been found in five, apparently unrelated, north‐western European Caucasoid subjects, residing in Wales, on HLA haplotypes bearing: A*0201, Cw*0501 with DRB1*0401, DQA1*03, DQB1*0301 in four instances and DRB1*0701, DQA1*0201, DQB1*0202 in one instance. The unique serological reactivity of ‘HLA‐B44BO’ was established using up to nine B*4408 subjects and was easily identified using a variety of B44 and B62 antisera. The phenotype and gene frequencies of B*4408, in a sample of 40 473 subjects residing in Wales, were 0.01235% and 0.00006, respectively.