Molecular analysis of HLA class II polymorphism in Croatians

Abstract: HLA-class II polymorphisms have been studied in a population of 141 unrelated healthy Croatians using PCR amplification, followed by non-radioactive oligonucleotide hybridization. Thirty one DRB1, 8 DQA1, 13 DQB1 and 16 DPB1 alleles were found in the tested population. DRB1*1601, 0701, 1501, 0101 and 1104 are the most frequent alleles at the DRB1 locus. At the DQA1 locus two alleles predominate: DQA1*0501 and 0102, while the most frequent DQB1 allele is *0301. Analysis of HLA-DPB1 polymorphism showed that, as in other Europeans, DPB1* 0401 is the most frequent allele. Four different two locus haplotypic associations (DRB1-DRB3, DRB1-DRB5, DRB1-DQB1 and DQA1-DQB1) as well as three locus DRB1-DQA1-DQB1 haplotypic associations were assigned on the basis of known linkage disequilibria. Several unusual two-locus associations have been observed: DRB1*0301-DRB3* 0202, DRB1*1501-DRB5*02, DRB1*1601-DRB5*0101, DRB1*1502-DRB5*0101, DQA1*0103-DQB1*0503 and DQA1*0501-DQB1*0302. Among 236 examined DRB1-DQA1-DQB1 haplotypic combinations, the most frequent was DRB1*1601-DQA1*0102-DQB1*0502 that was found with statistically significant higher frequency than in other Europeans. Twenty-eight distinct probable haplotypes were observed just once, suggesting that the main characteristic of Croatian population is great heterogeneity of haplotypes. This study will serve as a reference for further anthropology studies, HLA and disease associations studies and for donor/recipient matching in organ and bone marrow transplantation.     

HLA class II allele and haplotype frequencies in Koreans based on 107 families

We have investigated the distribution of HLA class II alleles and haplotypes in 107 Korean families (207 parents and 291 children) for the HLA-DRB1, DRB3/B4/B5, DQA1, DQB1 and DPB1 loci. Numbers of alleles observed for each locus were DRB1: 25, DQA1: 14, DQB1: 15, and DPB1: 13. Only two to three alleles were observed for the DRB3 (*0101, *0202, *0301), DRB4 (*0103, * 0103102 N), and DRB5 (*0101, *0102) loci. These alleles showed strong associations with DRB1 alleles: DRB3*0101 with DRB1*1201, *1301 and *1403; DRB3*0301 with DRB1*1202 and *1302; DRB3*0202 with DRB1*0301, *1101, *1401 and *1405; DRB5*0101 and *0102 were exclusively associated with DRB1*1501 and *1502, respectively. The seven most common DRB1-DQB1 haplotypes of frequencies > 0.06 accounted for 52% of the total haplotypes. These haplotypes were exclusively related with the seven most common DRB1-DRB3/B4/B5-DQA1-DQB1 haplotypes: DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 (0.085), DRB1*0405-DRB4*0103-DQA1*0303-DQB1*0401 (0.082), DRB1*09012-DRB4*0103-DQA1*0302-DQB1*03032 (0.082), DRB1*0101-DQA1*0101-DQB1*0501 (0.075), DRB1*0701-DRB4*0103-DQA1*0201-DQB1*0202 (0.065), DRB1*0803-DQA1*0103-DQB1*0601 (0.065), and DRB1*1302-DRB3*0301-DQA1*0102-DQB1*0604 (0.065). When these haplotypes were extended to the DPB1 locus, much diversification of haplotypes was observed and only one haplotype remained with a frequency of > 0.06: DRB1*0405-DRB4*0103-DQA1*0303-DQB1*0401-DPB1*0501 (0.062). Such diversification would have resulted from cumulated events of recombination within the HLA class II region, and the actual recombination rate observed between the HLA-DQB1 and DPB1 loci was 2.3% (10/438 informative meioses, including 2 recombinants informative by analysis of TAP genes). Comparison of the distribution of DRB1-DQB1 haplotypes with other populations revealed that Koreans are closest to Japanese people. However, Koreans share a few haplotypes with white people and Africans, which are rare in Japanese: DRB1*0701-DQB1*0202 and DRB1*1302-DQB1*0609. The results obtained in this study will provide useful information for anthropology, organ transplantation and disease association studies.     

Polymorphism and distribution of HLA-DR2 alleles and haplotypes in a Greek population

Abstract: HLA-DR2 serological subtyping has indicated that the DR16 serotype appears at a higher frequency relative to the DR15 serotype in the Greek population, differing from the distribution observed in most other Caucasian groups. In this study, we have analyzed by the PCR-SSP technique a DR2-positive group of unrelated Greek individuals selected from our normal control panel for the different DRB1, DRB5, DQB1 and DQA1 DR2-associated alleles present. Six of the 50 individuals analyzed were homo-zygous for DR2, contributing a total of 56 haplotypes for DR2. The observed frequencies of the DR2-related DRB1 alleles were as follows: 58.9% for the DRB1*1601, 7.1% for the DRB1*1602, 25.0% for the DRBl*1501 and 7.1% for the DRB1*1502 allele. The rare allele DRB1*1605 was detected in one heterozygous sample and its presence was definitively established by DNA sequencing. The alleles *1503, *1504, *1505, *1603 and *1604 were not detected. Three DRB5 alleles were identified: DRB5*0202 (67.8%), DRB5*0101 (25.0%) and DRB5*0102 (7.1%). Ten different DRB1/DQB1/ DQA1 DR2-associated haplotypes were denned. The most frequently observed haplotype was DRBl*1601-DQBl*0502-DQAl*0102 (relative frequency =57%) followed by DRB1*1501-DQB1*0602-DQA1*0102 (relative fre-quency=14.3%). In conclusion, the refined analysis of the DR2-associated DRB1 alleles in the Greek population revealed the prevalence of the DRB1*1601 allele. The rare allele DRB1*1605 was demonstrated once. A considerable variety of different DR2-related DR/DQ haplotypes was detected and the overall haplotypic frequencies in the Greek population are distributed differently compared to those reported for most other Caucasian populations.     

The Dai minority population of Southwest China: Heterogeneity of DR2-Associated HLA-DRB1,DRB5, DQA1, and DQB1 haplotypes

HLA-DR2 is the most common DR specificity (60.3%) identified in the Dai minority population of Xishuangbanna, Yunna Province, China. We characterized the DRB1, DRB5, DQA1, and DQB1 alleles of 44 unrelated DR2-positive individuals, 11 of whom (15%) were DR2 homozygous. Four DRB1 and four DRB5 alleles encoding DR2 were identified in this population. The most frequent DR2-associated DRB1 alleles were *1602 (gf = 0.164) and *1502 (gf = 0.151). DRB1*1501 (gf = 0.048) and a new allele designated DRB1*1504 (gf = 0.014) were also detected, but *1601 and *1503 were absent. The most frequent DR2-associated DRB5 alleles were *0101 (gf = 0.233) and *0102 (gf = 0.110). Nine different DR2-associated DR/DQ haplotypes were identified. The two most common DR2 haplotypes were DRB1*1602,DRB5*0101,DQA1*0102,DQB1*0502(hf = 0.142) and DRB1*1502,DRB5*0102,DQA1*0101, DQB1*0501 (hf = 0.075). The new DRB1*1504 allele was found on a single haplotype: DRB1*1504, DRB5*0101,DQA1*0102,DQB1*0502 (hf = 0.017). The Dw2, Dw12, Dw21, and Dw22 haplotypes, present in many other Asian and Mongoloid populations, were not identified in this unique group. However, the Dai minority population is characterized by a relatively large number of diverse DR2 haplotypes and a new DRB1 allele encoding DR2.     

Polymorphism of DR52-associated haplotypes in a Croatian population

We investigated DR52 haplotype polymorphism in a population of 78 Croatian families with at least one parent and one offspring positive for a DR52-associated allele, using the PCR–SSOP method. The haplotypes DRB1*0301-DQA1*0501-DQB1*0201, DRB1*11-DQA1*0501-DQB1*0301 and DRB1*1201-DQA1*0501-DQB1*0301 seem to be conserved haplotypes in this Croatian population, while DRB1*13 haplotypes showed high diversity. Among 10 different DRB1*13 haplotypes, four consist of common alleles, while six have an unusual combination of DRB1-DQA1-DQB1 alleles. Three haplotypes (DRB1*1301-DQA1*0103-DQB1*0503, DRB1*1302-DQA1*0102-DQB1*0502 and DRB1*1303-DQA1*0102-*DQB1*0502) have not been reported. These results on DR52-associated haplotype polymorphisms in a Croatian population must be taken into consideration in organ transplantation, especially when searching for unrelated bone marrow donors.     

Polymorphism of DR52-associated haplotypes in a Croatian population.

We investigated DR52 haplotype polymorphism in a population of 78 Croatian families with at least one parent and one offspring positive for a DR52-associated allele, using the PCR-SSOP method. The haplotypes DRB1*0301-DQA1*0501-DQB1*0201, DRB1*11-DQA1*0501-DQB1*0301 and DRB1*1201-DQA1*0501-DQB1*0301 seem to be conserved haplotypes in this Croatian population, while DRB1*13 haplotypes showed high diversity. Among 10 different DRB1*13 haplotypes, four consist of common alleles, while six have an unusual combination of DRB1-DQA1-DQB1 alleles. Three haplotypes (DRB1*1301-DQA1*0103-DQB1*0503, DRB1*1302-DQA1*0102-DQB1*0502 and DRB1*1303-DQA1*0102-*DQB1*0502) have not been reported. These results on DR52-associated haplotype polymorphisms in a Croatian population must be taken into consideration in organ transplantation, especially when searching for unrelated bone marrow donors.     

HLA-DR2 HAPLOTYPIC DIVERSITY IN POPULATIONS OF SOUTH-EAST ASIA,NORTHERN CHINA,MELANESIA AND AUSTRALIAN ABORIGINES USING PCR-RFLP FOR DRB1, DRB5, DQA1 AND DQB1. A NOVEL DRB1 ALLELE: DRB1 * 16022

The polymorphism of the human leucocyte antigen HLA-DR2 and the heterogeneity of HLA-DR2 class II-related haplotypes (HLA-DRB1-DRB5-DQA1-DQB1) were investigated in four populations of east and south-east Asia (SEA) and five Melanesian populations using TaqI restriction fragment length polymorphism (RFLP) analysis, and the polymerase chain reaction (PCR) amplification-based techniques PCR-RFLP and sequence-specific oligonucleotide (SSO) typing. The haplotype DRB1*1502-DRB5*0101-DQA1*0102-DQB1*0601 was common in Malaysians, Javanese, Thursday Islanders, Madang, Goroka and the Australian Aborigines, while DRB1*16021-DRB5*0101-DQA1*0102-DQB1*0502 was common in the Thai and Thursday Islanders. DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 was present at a high frequency in Northern Chinese, Goroka, Watut and Australian Aborigines. The study describes four rare or unusual haplotypes: HLA-DRB1*1501-DRB5*0101-DQA1*0101-DQB1*0601, DRB1*1502-DRB5*0101-DQA1*0101-DQB1*0502, DRB1*1502-DRB5*0102-DQA1*0102-DQB1*0502 and DRB1*1501-DRB5*0101-DQA1*0101/2-DQB1*0503; the latter two were confirmed by segregation in two Javanese families. A new DR2 allele, initially detected by PCR-RFLP and confirmed by DNA sequencing as DRB1 * 16022 (previously designated DRB1 * 16Madang), was seen in a Madang individual. A new HLA-DR2 TaqI RFLP subtype, locally designated as DR15U, is also described. This RFLP subtype segregated in a Javanese family and correlated with a typically SEA haplotype, DRB1*1502-DRB5*0102-DQA1*0101-DQB1*0501. The allele HLA-DR16Thai, determined by TaqI DRB RFLP, was found by PCR-RFLP and SSO typing to correlate with a unique SEA haplotype, HLA-DRB1*16021-DRB5*0101-DQA1*0102-DQB1*0502, and was observed in the Thai, Malaysian, Thursday Islander, Javanese and Northern Chinese populations.     

应用SBT直接测序分型法研究中国南方汉族人群HLA五个基因座单倍型

目的 研究中国南方汉族人群HLA-A、B、Cw、DRBl、DQBl等位基因多态性及单倍型的分布特征.方法 应用聚合酶链反应-直接测序分型(polymerase chain reaction sequence-based typing,PCR-SBT)法对186名中国南方汉族健康人群HLA-A、B、Cw、DRBl、DQBl进行基因分型.结果 检出的HLA-A、B、Cw、DRBl、DQBl等位基因分别有28、49、24、29、20种.经统计分析A*0207-B*4601(10.81%),A*3303-B*5801(6.14%),B*4601-DRBl*0901(6.22%),B*4001*DRBl*0901(3.78%),DRBl*0901-DQBl*0303(12.16%)和DRBl*1202-DQBl*0301(8.38%)单倍型呈强连锁不平衡单倍型(RLF≥0.5,X<'2>>3.84,P<0.05);A*0207-B*4601-Cw*0102(10.75%),A*3303-B*5801-Cw*0302(5.14%),A*0207-B*4601-DR*0901(5.07%),A*3303-B*5801-DRBl*0301(2.96%),A*0207-B*4601-Cw*0102-DRBl*0901-DQBl*0303(4.87%)和A*1101-B*1301-Cw*0304-DRBl*1501-DQBl*0601(2.43%)单倍型分别是中国南方汉族人群常见单倍型.结论 中国南方汉族人群HLA 5个基因座单倍型分布具有高度的遗传多态性且有其自身分布特点.本研究获得的较完整的HLA 5个基因座单倍型分布数据,将为人类学、HLA疾病相关性和器官移植等研究提供遗传学参考数据.     

Analysis of HLA-DR2-associated polymorphisms by oligonucleotide hybridization in an Asian Indian population

Among major histocompatibility complex class II antigens, HLA-DR2 appears to have a much larger degree of polymorphism than usually recognized by routine serology or restriction fragment length polymorphisms. We have utilized oligonucleotide probes to further identify the DR2 specificity and its molecular subtypes on the basis of specific DNA sequences as they occur in a select sample from the Asian Indian population. In addition, oglinucleotide typing of HLA-DQA1 and -DQB1 genes allowed us to determine specific associations of DRB1, DRB5, DQA1, and DQB1 alleles in DR2 individuals. A set of 60 oligonucleotide probes were hybridized to polymerase chain reaction (PCR)-amplified DNA from DR2 homozygous or heterozygous individuals. The most common DR2 subtypes that occured in this selected population are: DRB1^*1501 (60%), DRB1^*1502 (33.8%), and DRB1^*1602 (6.2%). No example of DRB1^*1601 was detected. By combining these results with the allelic variations at DQA1 and DQB1, we were able to detect at least seven different haplotypes, the most common being DRB1^*1502-DRB5^*0102- DQA1^*0103-DQBI^*0601 and DRBI^*1501-DRB5^*0101 DQA1^*0102-DQB1^*0502. At least five unexpected combinations, not reported among Western Caucasians, were noticed in this sample. Thus oligonucleotide typing is a valuable tool for defining further polymorphisms in the HLA-D region as exemplified by its applications to typing DR2-positive patients with tubercoloid leprosy and pulmonary tubercolosis.     

Striking diversity of DR15 haplotypes in Croatians

Analysis of HLA class II polymorphism revealed DR2 as the most frequent antigen in Croatians (20, 9%). The observed DR2 subtypes and their frequencies were as follows: DRB1*1601 – 9.9%; 1501 – 8.5%; 1602 – 1.8%, 1502 – 1.4% and 1503 – 0.7%. Furthermore, analysis of probable DRB1-DQA1-DQB1 haplotype associations in unrelated individuals revealed a high diversity of DR15 haplotype associations. Now, to confirm this observation from unrelated individuals, family studies have been performed. Sixty-eight families, with at least one parent and one offspring DR2 positive, have been studied. DRB1*1601-DQA1*0102-DQB1*0502 seems to be conserved haplotype in Croatians while DRB1*15 haplotypes showed extremely high diversity. Seven rare DR15 haplotypes are observed; six of these appear twice and one only once. Two haplotypes appear to be unique to Croatians: DRB1*1501-DQA1*0102-DQB1*0501 and DRB1* 1501-DQA1*0102-DQB1*0604. This confirmation of extremely high diversity of DR15 haplotypes in Croatians is a valuable tool for unrelated bone marrow transplantation and DR2 disease association studies.     

Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population

High-resolution human leukocyte antigen (HLA) typing exposes the unique patterns of HLA allele and haplotype frequencies in each population. In this study, HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were analyzed in 485 apparently unrelated healthy Korean individuals. A total of 20 HLA-A, 43 HLA-B, 21 HLA-C, 31 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. Eleven alleles (A*0201, A*1101, A*2402, A*3303, B*1501, Cw*0102, Cw*0302, Cw*0303, DQB1*0301, DQB1*0302, and DQB1*0303) were found in more than 10% of the population. In each serologic group, a maximum of three alleles were found with several exceptions (A2, B62, DR4, DR14, and DQ6). In each serologic group exhibiting multiple alleles, two major alleles were present at 62-96% (i.e. A*0201 and A*0206 comprise 85% of A2-positive alleles). Multiple-locus haplotypes estimated by the maximum likelihood method revealed 51 A-C, 43 C-B, 52 B-DRB1, 34 DRB1-DQB1, 48 A-C-B, 42 C-B-DRB1, 46 B-DRB1-DQB1, and 30 A-C-B-DRB1-DQB1 haplotypes with frequencies of more than 0.5%. In spite of their high polymorphism in B and DRB1, identification of relatively small numbers of two-locus (B-C and DRB1-DQB1) haplotypes suggested strong associations of those two loci, respectively. Five-locus haplotypes defined by high-resolution DNA typing correlated well with previously identified serology-based haplotypes in the population. The five most frequent haplotypes were: A*3303-Cw*1403-B*4403-DRB1*1302-DQB1*0604 (4.2%), A*3303-Cw*0701/6-B*4403-DRB1*0701-DQB1*0201/2 (3.0%), A*3303-Cw*0302-B*5801-DRB1*1302-DQB1*0609 (3.0%), A*2402-Cw*0702-B*0702-DRB1*0101-DQB1*0501 (2.9%), and A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0201/2 (2.7%). Several sets of allele level haplotypes that could not be discriminated by routine HLA-A, -B, and -DRB1 low-resolution typing originated from allelic diversity of A2, B61, DR4, and DR8 serologic groups. Information obtained in this study will be useful for medical and forensic applications as well as in anthropology.     

HLA-DRB1, DQA1, DQB1 DNA polymorphism in the Bulgarian population

We describe for the first time the use of PCR based techniques to analyze the MHC class II polymorphism of the Bulgarian population. The present study provides the HLA-DRB, DQB1 allele frequencies in 116 Bulgarian individuals and DQA1 alleles frequencies in 100 subjects. DNA from these individuals was typed for DRB and DQB1 typed by the PCR- Allele Specific Amplification (PCR-ASA) method and DQA1 by PCR followed by hybridization using Sequence Specific Oligonucleotides (PCR-SSO). Allele and haplo-type frequencies and linkage disequilibria are computed by the standard methods used for the XIth International Histocompatibility Workshop. The highest frequencies are 0.159, 0.109 and 0.085 for DRB1*1101, DRB1*1601 and DRB1*1301 respectively. Among the eight DQA1 alleles detected, DQA1*0501 (0.344) is found to be much more frequent than the two most frequent alleles DQA1*0102 (0.225) and DQA1*0101 (0.151). Twelve DQB1 alleles are found and three of them, DQB1*0301 (0.280), DQB1*0502 (0.153) and DQB1*0201 (0.133) showed the highest frequencies. The haplo-type DRB1*1101-DQA1*0501-DQB1*0301 (0.079) predominate clearly, followed by DRB1*1601-DQA1*0102-DDQB1*0502 (0.055) and DRB1*0101-DQA1*0101-DQB1*0501. These results indicate that the Bulgarian population is characterized by features representative of the European anthropological type with a substantial contribution from the Southern Belt of Europe.     

Heterogeneity of HLA-DR2 haplotypes in Caucasoid Americans, African Americans, Chinese Americans, Native Americans and Xiamen Chinese.

HLA-DR, -DQ specificities were determined by PCR amplification with SSOP in 4560 individuals: Caucasoid Americans (CA), African Americans (AA), Chinese Americans (ChA), Native Americans (NA) and Xiamen Chinese (XC). DR2 subtypes were compared amongst the five ethnic populations. The DRB1*1501-DRB5*0101 haplotype was found to be the most frequent in all populations except African Americans, in which DRB1*1503-DRB5*0101 was the predominant haplotype, accounting for 65% of DR2 subtypes. In contrast to Caucasoid Americans, the DRB1*1602 is strongly associated with the DRB5*0101 allele in Chinese populations. The presence of DRB5*0203 and DRB1*1602-DRB5*0101 haplotypes in Chinese populations, especially in Xiamen Chinese, suggests that various DR2 haplotypes may be generated via multiple gene conversion events together with point mutations and reciprocal recombination. The strong DR and DQ associations are found in DRB1*1501/DQB1*0602 (66.22%) for CA, DRB1*1503/DQB1*0602 (56.58%) for AA, DRB1*1501/DQB1*0602 (30.20%) and DRB1*1602/DQB1*0502 (15.76%) for ChA, DRB1* 1501/DQB1*0602 (41.55%) and DRB1*1602/DQB1*0301 (40.25%) for NA, and DRB1*1501/DQB1*0602 (30.26%) and DRB1*1602/DQB1*0502 (25.81%) for XC.     

Heterogeneity of HLA-DR2 haplotypes in Caucasoid Americans,African Americans,Chinese Americans,Native Americans and Xiamen Chinese

HLA-DR, -DQ specificities were determined by PCR amplification with SSOP in 4560 individuals: Caucasoid Americans (CA), African Americans (AA), Chinese Americans (ChA), Native Americans (NA) and Xiamen Chinese (XC). DR2 subtypes were compared amongst the five ethnic populations. The DRB1*1501-DRB5*0101 haplotype was found to be the most frequent in all populations except African Americans, in which DRB1*1503-DRB5*0101 was the predominant haplotype, accounting for 65% of DR2 subtypes. In contrast to Caucasoid Americans, the DRB1*1602 is strongly associated with the DRB5*0101 allele in Chinese populations. The presence of DRB5*0203 and DRB1*1602-DRB5*0101 haplotypes in Chinese populations, especially in Xiamen Chinese, suggests that various DR2 haplotypes may be generated via multiple gene conversion events together with point mutations and reciprocal recombination. The strong DR and DQ associations are found in DRB1*1501/DQB1*0602 (66.22%) for CA, DRB1*1503/DQB1*0602 (56.58%) for AA, DRB1*1501/DQB1*0602 (30.20%) and DRB1*1602/ DQB1*0502 (15.76%) for ChA, DRB1* 1501/ DQB1*0602 (41.55%) and DRB1*1602/ DQB1*0301 (40.25%) for NA, and DRB1*1501/ DQB1*0602 (30.26%) and DRB1*1602/DQB1*0502 (25.81%) for XC.     

Novel HLA-DR2 and -DR3 haplotypes among Norwegian Caucasians

In the Northern European population, all DR2 haplotypes encoded by DRB1*1501 have previously been found to carry the DQA1*0102 and DQB1*0602 alleles, and DR3 haplotypes have been found to carry the DQA1*0501 and DQB1*0201 alleles. Here we report a novel recombinant DR2 haplotype carrying the DRB1*1501, DQA1*0102 and DQB1*0603 alleles as well as a novel recombinant DR3 haplotype carrying the DRB1*0301, DRB3*0101, DQA1*0102 and DQB1*0602 alleles.     

HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in the Kinh population in Vietnam

Allele and haplotype frequencies of the human leukocyte antigens (HLA) were studied in the Kinh Vietnamese population. We analyzed 170 unrelated healthy individuals. DNA-based HLA typing was performed using a microsphere-based array genotyping platform with sequence-specific oligonucleotide probes to distinguish HLA-A, -B, -C, -DRB1 and -DQB1 alleles. A total of 21 HLA-A, 37 HLA-B, 18 HLA-C, 25 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. HLA-A*1101, A*2402, A*3303, B*1502, B*4601, Cw*0102, Cw*0702, Cw*0801, DRB1*1202, DQB1*0301, DQB1*0303, and DQB1*0501 were found with frequencies higher than 10%. Two representative haplotypes bearing two to five HLA loci were A*1101-B*1502 and A*3303-B*5801 for HLA-A-B; Cw*0801-B*1502 and Cw*0102-B*4601 for HLA-C-B; B*1502-DRB1*1202 and B*4601-DRB1*0901 for HLA-B-DRB1; DRB1*1202-DQB1*0301 and DRB1*0901-DQB1*0303 for HLA-DRB1-DQB1; A*1101-Cw*0801-B*1502 and A*3303-Cw*0302-B*5801 for HLA-A-C-B; A*1101-B*1502-DRB1*1202 and A*2901-B*0705-DRB1*1001 for HLA-A-B-DRB1, A*1101-Cw*0801-B*1502-DRB1*1202-DQB1*0301 and A*2901-Cw*1505-B*0705-DRB1*1001-DQB1*0501 for HLA-A-C-B-DRB1-DQB1. Allele distribution and haplotype analysis demonstrated that the Vietnamese population shares HLA patterns with southern Chinese, Thai, Javanese and Micronesians, while it also retains unique characteristics.     

Multi-locus analysis of HLA class II genes in DR2-positive IDDM haplotypes in Finland

Abstract: In this study we characterized the haplotypes found in IDDM patients that normally confer resistance to the disease in order to localize the polymorphisms relevant for the protection. We studied 15 DR2-positive subjects with IDDM for their DRB1, DRB5 and DQB1 genes using RFLP, polymerase chain reaction (PCR), oligonucleotide typing, and in some specific cases direct sequencing after allele-specific PCR. In addition we analyzed 39 DR2-positive, IDDM non-associated haplotypes representing those haplotypes that are not inherited to probands and hence are present only in healthy family members. The frequency of the DRB1*1501-DRB5*0101-DQB1*0602 haplotype was slightly decreased among diabetic patients (80% vs. 92%). In addition, two unconventional haplotypes DRB1*1501-DRB5*0101-DQB1*05031 and DRB1*1501-DRB5*0101-DQB1*0502 were found in patients with IDDM while all the control ones were conventional. The sequencing of the DQB1*0602 allele present in IDDM haplotypes showed no differences when compared to the controls. These results support the primary but not absolute role of DQ in the protection against IDDM. An additional role of factors centromeric to DQB1 gene was suggested by findings based on the biallelic TaqI RFLP polymorphism of the DQA2 gene. All DR2-DQB1*0602 IDDM haplotypes were associated with the 2.1-kb fragment while in the control group the 2.1-kb and 1.9-kb fragments were evenly distributed.     

Polymorphism of HLA-A, -B, -DRB1, -DQA1 and -DQB1 haplotypes in a Croatian population.

We describe for the first time extended haplotypes in a Croatian population. The present study gives the HLA-A, -B, -DRB1, -DQA1 and -DQB1 allele and haplotype frequencies in 105 families with at least two offspring. All individuals were studied by conventional serology for HLA class I antigens (A and B), while class II alleles (DRB1, DQA1, DQB1) were typed using the PCR-SSOP method. HLA genotyping was performed by segregation in all 105 families. For extended haplotype analysis, 420 independent parental haplotypes were included. Fourteen HLA-A, 18 HLA-B, 28 DRB1, 9 DQA1 and 11 DQB1 alleles were found in the studied population. Most of the DRB1 alleles in our population had an exclusive association with one specific DQA1-DQB1 combination. This strong linkage disequilibrium within the HLA class II region is often extended to the HLA-B locus. A total of 10 HLA-A, -B, -DRB1, -DQA1, -DQB1 haplotypes were observed with a frequency 相似文献   

西双版纳傣族及上海汉族群体HLA－DR2相关的DR／DQ单倍型分析

对４４名西双版纳傣族和９名上海地区汉族ＤＫ２阳性个体进行了与其相关的ＤＲ／ＤＱ单倍型组合的分析。傣族群体中ＤＲＢＩ－ＤＲ２亚型分布以＊１６０２与＊１５０２为最常见，其等位基因频率分别为４３．６％与，４０．０％和汉族群体中以＊１５０１为主明显不同。傣族群体中共检出１０种与ＤＲ２相关联的ＤＲ／ＤＱ单倍型；最常见的是ＤＲＢ１＊１６０２、ＤＲＢ５＊０１０１、ＤＱＡ１＊０１０２、ＤＱＢ１＊０５０２（３４．５％）与汉族及其他群体明显不同，本研究表明傣族不仅具有高频率的ＤＲ２，而且与ＤＲ２相关联的ＤＲＢ１、ＤＲＢ５、ＤＱＡ１、ＤＱＢ１单倍型组合有其独特性。     

DNA typing for class II HLA antigens with allele-specific or group-specific amplification. IV. Typing for alleles of the HLA-DR2 group

In this study we present an approach for the definition of the alleles belonging to the HLA-DR2 group by DNA typing with oligonucleotide probes. Following methodology similar to that we used previously for the definition of other HLA-DR subsets, we have now developed primers for DR2-DRB1 and DR2-DRB5 amplification, and probes for the identification of sequences that distinguish the subtypes of this group of genes. The method used defines all the previously described alleles at both DR2-associated DRB loci. In addition, we have identified a variant of DRB1-DR2-Dw2. This new allele has been called DRB1*15.3. It is different from DRB1*1501 in codon 30, where it carries histidine instead of tyrosine. Eight different haplotype combinations of DRB5, DRB1, and DQB1 were identified within the DR2 group and their occurrence in four normal panels of different ethnic origin has been described. Haplotypes containing DRB1*15.3 occurred most frequently in black panel members in whom it was associated with either DQB1*0602 or DQB1*0501. Two unusual haplotypes were observed: one containing elements of DR2-Dw21 (DQB1*0502) and of DR2-Dw22 (DRB1*1602) and one containing elements of Dw21 (DRB1*1601, DQB1*0502) and Dw2 (DRB5*0101). The methods described permit simple and rapid determination of the alleles of the HLA-DR2 group and should be useful for population studies and for investigation of DR2-associated diseases.