HLA haplotypes in Koreans based on 107 families

Abstract: There are marked differences in the distribution of HLA haplotypes among different populations, and multilocus HLA haplotypes can best be studied by family analysis. In the present study, 107 Korean families were analyzed for HLA-A, B, C, DR, and DQ antigens and haplotypes. Allele frequencies of more than 10% for class I antigens were A2, A24, A33, B44, B62, Cw1, Cw7, Cw9, Cw10, and C blank (CBL) and those for class II antigens were DR4, DR8, DR13, DR15, DQ1, DQ3, DQ4 and DQ7. In the analysis of HLA haplotypes, 18 kinds of A-B-DR and 11 kinds of A-C-B-DR-DQ haplotypes occurred at frequencies of more than 1%, comprising 34% and 24% of the total theoretical haplotypes, respectively. The five most common A-B-DR haplotypes were exclusively related with the five most common A-C-B-DR-DQ haplotypes (frequency>2%). These remarkably conserved five-locus haplotypes in Koreans were A33-CBL-B44-DR13-DQ1 (5.4%), A24-Cw7-B7-DR1-DQ1 (3.5%), A33-Cw7-B44-DR7-DQ2 (3.0%), A33-Cw10-B58-DR13-DQ1 (2.3%), and A30-Cw6-B13-DR7-DQ2 (2.3%). Comparison of the distribution of A-B-DR haplotypes among East Asian populations revealed that Koreans are closest to Japanese, but show a higher degree of polymorphism in the distribution of HLA haplotypes compared to Japanese. The results obtained in this study will be useful as basic data on Koreans for anthropology and organ transplantation.     

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 polymorphism and probability of finding HLA-matched unrelated marrow donors for Chinese in Taiwan

Tzu Chi Taiwan Marrow Donor Registry (TCTMDR) was established in 1993 to recruit and HLA-type volunteers who would be willing to donate bone marrow. TCTMDR is currently the largest marrow registry for Chinese in the world, with over 150,000 prospective donors registered as of July 1997. We present here the gene and haplotype frequencies based on 80,353 HLA class I-typed and 18,217 HLA class II-typed healthy Chinese in Taiwan. The resulting frequencies are used for estimating the probability of finding an HLA-matched donor for a patient. The common HLA class I antigens include Al (gene frequency: 32.9%), A2 (29.7%), A24 (17.5%) and A33 (11.0%); B60 (18.1%), B46 (12.8%), B58 (9.8%) and B13 (7.8%); Cw3 (51.4%), Cwl (11.6%) and Cw7 (8.6%). The common HLA class II antigens are DR4 (16.6%), DR9 (15.6%), and DR12 (14.0%); DQ7 (20.7%), DQ9 (12.7%), and DQ5 (12.1%). The common two-locus haplotypes observed with a P -value less than 0.001 are A2-B46 (haplotype frequency: 8.5%), A33-B58 (7.5%), A11-B60 (6.6%); B58-DR17 (7.0%), B46-DR9 (6.4%) and B60-DR4 (4.9%). The common three-locus haplotypes are A33-B58-DR17 (5.3%), A2-B46-DR9 (3.9%) and A11-B60-DR4 (2.0%). As expected, the gene frequency pattern of Taiwanese is more closely related to that of southern Hans than to the pattern of northern Hans, Japanese, Caucasians and African-Americans. Using our registry, 323 of 571 domestic patients (57%) successfully identified one or more matched donors. The empirical result correlated well with a mathematical simulation having an estimated 59% match when donor pool reaches 150,000.     

Distribution of HLA class I alleles and haplotypes in Korean.

The antigen (phenotype), gene (allele) and haplotype frequencies of HLA class I were analysed in 4,622 Koreans. With allele frequencies of over 0.05, the most frequent HLA-A,-B and -C antigens were A2, A24, A33, A11, A26, A31; B62, B51, B44, B54, B61, B35, B58, B60; Cw3, Cw1, Cw4, Cw7. Of these A2, A24, Cw1 and Cw3 were present in very high frequencies, respectively (0.3211, 0.2200, 0.2204, and 0.3737). The most common haplotypes with frequencies larger than 0.02 were A2-Blank, A33-B44, A33-B58, A11-B62, A24-B51, A24-B54, A2-B27, B54-Cw1, B58-Cw3, B51-Blank, B61-Cw3, B62-Cw4, B35-Cw3, B44-Blank, B60-Cw3, B27-Cw1, A2-Cw3, A2-Cw1, A24-Cw1, A33-Cw3, A26-Cw3, and A11-Cw4. A significant negative linkage disequilibrium was found for the haplotypes of A2-B7, A2-B44, A2-B58, A24-B13, A24-B27, A33-B54 and A33-B62, of which frequencies were larger than 0.003. The B-C and A-C haplotypes which showed the significant negative linkage disequilibrium were B44-Cw1, B51-Cw1, B44-Cw3,B62-Blank, A2-Cw4, A2-Blank, A11-Cw3, A11-Blank and A33-Cw1 and had frequencies higher than 0.01. The findings presented here could be used per se to estimate the populational relationships or as the control data for HLA-disease investigation. Furthermore they could provide the scope for the definition of new antigens.     

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.     

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.     

Distribution of HLA antigens in Spanish Gypsies: A comparative study

We have studied the HLA-class I and class II antigen distribution in a sample of 75 Spanish Gypsies and 74 Spanish non-Gypsies by serology, restriction fragment length polymorphism, and protein chain reaction and hybridization with allele-specific oligonucleotide probes. When both population samples are compared, we find that Gypsies have a statistically significantly higher frequency of A1, A11, B61, Cw6, DQ5 and haplotypes DR16 DQ5 Dw21 and DR14 DQ5 Dw9 DR52b. Frequency of A3, A29, B44, DR4, DQ2, DQ8 and haplotypes DR1 DQ5 and DR7 DQ2 DB17 DR53 are significantly lower in this ethnic group. The analysis of the serological data in the two populations demonstrates that Cw6 can be split into long Cw6 (Cw6.1) and short Cw6 (Cw6.2). Haplotype A1-Cw6-B61-DR14-DQ5 is the most characteristic in Gypsies, with a frequency of 13%. Estimation of the genetic distances shows that Spanish Gypsies are closer to Indian Caucasoid populations than to the Spanish non-Gypsy population. HLA data support the proposed historical origin of this ethnic group.     

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%     

643例中国北方汉族急性淋巴细胞白血病患者人类白细胞抗原连锁不平衡分析

目的 分析643例中国北方汉族急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患者组和20359名健康对照组的人类白细胞抗原(human leukocyte antigen,HLA)HLA-A-B、B-DR和AB-DR单倍型频率及连锁不平衡分布差异.方法 应用最大似然性算法(expectation-maximization,EM)计算患者组和对照组的HLA-A-B、B-DRB1和A-B-DRB1单倍型频率及连锁不平衡参数,采用X2检验比较其分布差异.结果 HLA-A30-B13、A2-B46、A33-B58,B13-DR7、B46-DR9、B52-DR15、B58-DR17,A30-B13-DR7、A33-B58-DR17和A1-B37-DR10单倍型是两组常见、共有呈强连锁不平衡单倍型.A30-B13、A2-B46、A33-B44、B13-DR7、A30-B13-DR7和A2-1346-DR9的单倍型频率和连锁不平衡水平,患者组低于对照组,差异有统计学意义(X2＞3.84,P＜0.05).A2-B52、A2-B27、A24-B8,B60-DR9、B27-DR4、B52-DR14、B44-DR17、B27-DR12、和A11-B27-DR12的单倍型频率和连锁不平衡水平,患者组高于对照组,差异有统计学意义(X2＞3.84,P＜0.05).结论 643例北方汉族ALL患者组HLA-A-B、B-DRB1、A-B-DRB1单倍型频率分布及连锁不平衡遗传特征和对照组具有高度的同源性.患者组与对照组之间的部分HLA单倍型频率及连锁不平衡分布存在统计学差异.本研究结果 为ALL与HLA疾病相关性及HLA相合供者的寻找提供了基础数据.     

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.     

HLA-B14 subtyping by semi-nested PCR-SSP and haplotype distribution in a Spanish population

HLA-B14 serological subtyping is very limited probably due to the internal position of the unique amino acid residue that differentiates B64 and B65 molecules. In order to carry out an accurate B14 subtyping we have designed a semi-nested PCR-SSP procedure that can differentiate B*1401 and B*1402 in any HLA-A, -B or -C antigen combination. A panel of 133 B14-positive and 31 B14-negative healthy and unrelated Spanish individuals were studied. Additionally, 45 B14-bearing haplotypes (-A,-B,-C,-DRB1,-DRB3/DRB4/DRB5,-DQA1,-DQB1) were available through family studies. The relative frequencies of HLA-B14 subtypes were 74% for B*1402 and 26% for B*1401, in agreement with those found in other Central European populations, but differing from those in Wales, where the relative presence of B64 goes to 41%. A total of 11/17 and 18/28 different haplotypes for B*1401 and B*1402, respectively, were identified. Both alleles showed the strongest association to Cw8 (43/45), indicating a primary ancestral B14-Cw8 association. However, B14 subtypes evidenced very distinguishable haplotype distributions. B*1401 is strongly associated with the common HLA class II haplotype DRB1*0701-DQA1*0201-DQB1*02 (13/17), while B*1402 is mainly associated to DRB1*0102 (16/28). Three major haplotypes were identified: A32-Cw8-B*1401-DR7-DQ2 (5/17), A33-Cw8-B*1402-DRB1*0102-DQ5 (5/28) and A2-Cw8-B*1402-DRB1*0102-DQ5 (5/28).     

Human leukocyte antigen-A, -B, and -Cw polymorphism in a Berber population from North Morocco using sequence-based typing

Class I human leukocyte antigen (HLA) polymorphism was examined in a Berber population from North Morocco, named Metalsa (ME). All data were obtained at high-resolution level, using sequence-based typing. The most frequent alleles were: HLA-A*0201 and A*0101; HLA-B*44 (B*4403 and B*4402); B*0801 and the B*50 allele group (B*5001 and B*5002); HLA-Cw*0602; and Cw*07 group (Cw*070101, Cw*070102, Cw*0702, Cw*0704, and Cw*0706), and Cw*040101. The novel HLA-B*570302 allele was identified. It differs at position 486 and position 855 from B*570301, resulting in synonymous Thr and Val. The analysis also evidenced some alleles common in Africans (A*3402, A*6802, A*7401, B*1503, B*4102, B*4202, B*7801, B*5802, Cw*1701, and Cw*1703) and some uncommon alleles (A*3004, B*2702, B*2703, B*5001,02, B*3503, and Cw*0706). The predominant HLA-A-Cw-B-DRB1-extended haplotypes in ME population were A*0101-Cw*0501-B*4402-DRB1*0402, A*240201-Cw*0701-B*0801-DRB1*030101, A*2301-Cw*040101-B*4403-DRB1*040501, A*0201-Cw*040101-B*4403-DRB1*1302, and A*3002-Cw*0602-B*5002-DRB1*0406. This study demonstrates a strong relatedness of ME to other Moroccan and North African populations, some characteristics of sub-Saharan Africans and evidenced the influence of various immigrations during centuries. Nevertheless, this study highlights some unique genetic traits of the ME population compared to other ethnic groups within Morocco, which could be of great interest for clinical aims, transplantation, and diseases.     

Study of HLA system in a Mataco population:

A search for antigens of the HLA system has been carried out in 53 Mataco Indians of Argentina living in a geographically isolated area in the northeast of the country. Samples were mostly collected from adults of both sexes who were not directly related.
Lymphocyte typing was performed using the microcytotoxicity technique of NIH. 118 sera specific for 15 antigens of the first HLA locus, 22 antigens of the second and 6 of the third were used.
The most frequently found alleles were HLA-A28, Aw31 and A2 for the first locus; B15 and B40 for the second; and Cw3 and Cw4 for the third.
In addition to previously published investigations on South American Indians, our typing work shows a remarkable homogeneous gene pool and a restricted range of polymorphism; therefore, a further set of haplotypes rendered us also restricted. The most frequent haplotypes that showed a significant statistical linkage desequilibrium were: A2-Cw4, A28-Bx, A2-Cw3, Aw31-Bw16, Aw24-Cw3, B15-Cw3, Bw16-Cw3 and A28-B5.
Some of these haplotypes have also been found in other indian populations.     

我国中部地区HIV感染者HLA Ⅰ类等位基因多态性与病毒载量的相关性研究

目的 分析我国中部地区既往采浆HIV感染者HLA Ⅰ类等位基因多态性及其与病毒载量的相关性.方法 应用PCR-SSP(序列特异性引物)技术对106例HIV感染者进行HLA Ⅰ类基因分型,分析HLA Ⅰ类等位基因多态性和单元型与血浆病毒载量的相关性.利用ELISPOT技术检测Gag蛋白特异性的CTL反应,并分析其与血浆病毒载量的相关性.结果 携带HLA Ⅰ类等位基因纯合子的感染者具有较高的病毒载量(P=0.0098);HLA-A*30、-B*13、-Cw*06、-Cw*14等位基因及A*30/B*13/Cw*06单元型与低病毒载量相关(P=0.0004,0.0103,0.0058,0.0371和0.0006);携带HLA-A*30/B*13/Cw*06单元型的感染者p2p7p1p6蛋白特异性的CTL反应与病毒载量负相关;携带HLA-Cw*14的感染者p17蛋白特异性的CTL反应与病毒载量负相关.结论 我国中部地区既往采浆HIV感染人群HLA-A*30、-B*13、-Cw*06、-Cw*14等位基因及A*30/B*13/Cw*06单元型携带者具有较低的病毒载量,其保护性与Gag蛋白特异性的CTL反应有关.     

HLA allele and haplotype frequencies in Algerians : Relatedness to Spaniards and Basques

The powerful genetic polymorphism of the HLA system has been used to identify individuals and populations. Ethnic groups may be characterized by specific HLA allele frequencies and particular extended HLA haplotypes; also, genetic relationships among these groups may be deduced. In the present study, serology and DNA typing were used to detect HLA-A, -B, -C, -DR, and -DQ alleles in each individual and to calculae characteristic haplotypes in Algerians. These results were compared to those previously obtained in other populations, particularly northern Mediterraneans; genetic distances and their respective dendrograms place Basques and Spaniards closer to Algerians than to other Europeans. Also, characteristic Basque and/or Spanish haplotypes are found in Algerians; i.e., A30-B18-Cw3-DR3-DQ2 and Al-B57-Ctv7-DR7-DQ2. This supports the evidence that the Algerian population, mainly its paleo-North African component (Berbers), has a common descent with Basques and Spaniards, probably reflecting a preneolithic relationship between Iberians and paleo-North Africans.     

Interethnic genetic differentiation: HLA class I antigens in the population of Mongolia

A total of 1668 individuals representing 10 major Mongolian ethnic groups were serologically typed for HLA-A, -B, and -C antigens. Antigens A2, A24, B61, B51, B58, Cw3, Cw7, and Cw6 were the most frequent specificities in Mongolians and no case of B42 was noted in all ethnic groups. The cluster analysis of Principal Components I and II shows that Mongolian speaking groups form one cluster vs Turkic-speaking Kazakhs. The analysis reveals a low, but significant differentiation of Mongolian ethnic groups as measured by F_ST = 0.0100 (P < 0.001). Gene diversity analysis shows that the genetic diversity of the Mongolian population can be attributed largely to its ethnic component, which makes up 64% of total genetic variation. The low degree of interpopulation variation and high level of intrapopulation diversity can be explained by the nomadic way of life of this indigenous population. Three-locus haplotypes A24-B61-Cw3, A33-B58-Cw3 are the most common haplotypic associations in Mongolians. The presence of antigens characteristic of Mongoloid, Caucasoid, and Negroid populations in Mongolians suggests a unique genetic background of this indigenous population. The three-locus haplotype distribution among Mongolians relative to other world populations supports the migration of ancient people from Central Asia to the New World, Korean Peninsula, and Southeast Asia. Am. J. Hum. Biol. 11:603–618, 1999. © 1999 Wiley-Liss, Inc.     

Extended DR3-D6S273-HLA-B haplotypes are associated with increased susceptibility to type 1 diabetes in US Caucasians

Human leukocyte antigen (HLA)-DR3 haplotypes are associated with susceptibility to type 1 diabetes (T1D). Reports from Northern European populations show that an allele (D6S273*2) at a microsatellite mapping to HLA class III marks an extended DR3-B18 haplotype associated with increased susceptibility to T1D. Consistent with previous reports, D6S273*2 marked a highly predisposing DR3 haplotype in European origin, multiplex families from the USA. Furthermore, we observed on DR3 haplotypes that other D6S273 alleles were also significantly associated with both increased transmission (D6S273*5; P < 0.02) and decreased transmission (D6S273*7; P < 0.05) to affected individuals. The differential transmission was most evident among DR3-B8 haplotypes. Neither HLA-B*1801 nor any alleles of D6S273 were associated with increased T1D predisposition on DR4 haplotypes. These data indicate that multiple alleles of D6S273 mark a susceptibility locus whose effect we were able to detect only among DR3 haplotypes but not limited to DR3-B18 haplotypes.     

Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on genotypic context: association of DPB1 and HLA class I loci among DR3- and DR4-matched Italian patients and controls

Patients with high-risk human leukocyte antigen (HLA)-DR-DQ genotypes for type 1 diabetes (T1D) were compared with HLA-matched controls to evaluate T1D risk for other HLA loci, including HLA-A, -B, -Cw, and DPB1. Patients (n = 133) with high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio (Rome) region of Italy. Screening of more than 9000 patients from the Lazio region and northern Italy yielded 162 controls with high-T1D-risk haplotypes. Although the overall distributions did not differ significantly, allele frequency differences were discovered between the controls from Lazio and controls from northern Italy for some alleles previously determined to affect T1D risk, such as A*3002, DPB1*0301, and DPB1*0402. Therefore, Lazio patient data were compared both with the Lazio subset of controls (n = 53) and with the entire group of controls for association analyses. Significant allele frequency differences between patients and DR-DQ-matched controls existed for specific alleles at all loci. Data for the DR3/DR3 subset of patients and controls demonstrated an increase of Cw*0702 in patients. Compared with controls, reduced patient frequencies were seen for several alleles, including A*0101, B*0801, and Cw*0701, all on the highly conserved, extended DR3 haplotype known as 8.1 in DR3/DR3, but not DR3/DR4, subgroup. DPB1*0101, often reported on 8.1 haplotypes, was also less frequent in DR3/DR3 patients than controls. Analysis of family-based data from the HBDI repository was consistent with the observed results from the Italian patients, indicating the presence of a T1D-protective locus at or near A*0101 and a second T1D-protective locus at or near DPB1*0101. These data indicate that T1D risk conferred by the 8.1 haplotype is genotype dependent.     

HLA antigen and haplotype frequencies in Greeks

A random panel of 189 healthy Greek subjects was HLA typed for A, B and DR antigens. The alleles of these loci were found to be in Hardy-Weinberg equilibrium. Compared with other European Caucasoid populations, the frequencies of A9, B5, B18, B35, DR2 and DR5 were raised and that of B8 lowered. Significant linkage disequilibrium was found between a number of A/B, B/DR and A/DR antigen combinations. Some of the antigen associations usually seen in Caucasoid populations were also present in this sample (A1-B8-DR3, B14-DR1, B15-DR4) although others were missing (A3-B7-DR2, B35-DR1, B44-DR4). In addition, some antigen combinations have not been previously described. The most frequent two locus haplotypes in the Greek population are B8-DR3 and B18-DR5.