HLA class II allele frequencies in the Lebanese population

Human leukocyte antigens (HLA) allele determination is becoming an increasingly important aspect in the field of transplantation as well as in the area of HLA association with a number of diseases. Through Lebanon's history, this country, situated at a crossroads between Europe, Asia and Africa, has been a host for various populations of different ethnicities. The aim of our study is to determine whether allele polymorphisms in the Lebanese population present a distinguishing feature. Although data on HLA phenotypic polymorphisms in Lebanon have been reported in the literature, our study is the first to examine frequencies of HLA polymorphisms in the country at the molecular level. Allele frequencies of the Lebanese population were analyzed and compared with those of other populations. HLA class II genotyping of DRB1* and DQB1* loci by PCR-sequence-specific primer (SSP) was performed on 191 unrelated Lebanese subjects of both sexes and of different regions and sects in Lebanon. The study revealed that DRB1*1101, DRB1*0401 and DRB1*0301 were the three most common DRB1* alleles observed (respective allele frequencies of 0.302, 0.164 and 0.096). In the DQB locus allele group, DQB1*0301 (allele frequency of 0.384) was highly predominant followed by the DQB1* 0501, DQB1*0201 and DQB1*0302 with respective allele frequencies of 0.199, 0.195 and 0.103. These results confirm previous serological studies and show the high prevalence of DRB1*1101 and DQB1*0301 in Lebanon, which could be explained by the high frequency of consanguineous marriages in the population. The presence of other common alleles is consistent with historical data showing that the Lebanese population is an admixture of various ethnicities.     

Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population.

The polymorphism of the HLA class II genes DRB1, DQA1, and DQB1 was investigated in 100 unrelated Iranian individuals from Fars province in Southern Iran, using the restriction fragment length polymorphism (RFLP) method. Subtyping of DRB1*04, *15, and *16 alleles was performed using PCR amplification with sequence specific primes (PCR-SSP). The allele and the haplotype frequencies were calculated. The most common DRB1 alleles were DRB1*11, DRB1*15, and DRB1*04 with a frequency of 25.0%, 14.5%, and 10.5%, respectively. In contrast, the allelic frequency of DRB1*12 and DRB1*08 was very low (1.5% for each). In the DR15 group DRB1*1501 was the most prevalent variant (6.0%). Concerning DR4, the most common alleles were DRB1*0405 and DRB1*0402 (3.5% for each). Interestingly, DRB1*0402 was associated with DQB1*0302 and DRB1*0405 was associated with DQB1*0302 and DQB1*02, the latter being a rare DRB1/DQB1 haplotype in Caucasian individuals. The most frequent DQB1 alleles were DQB1*0301 (31.0%), and DQB1*05 (22.0%). The most frequent DQA1 variants were DQA1*0501 (39.0%) and DQA1*0102 (14.5%). The most common haplotype was DRB1*11-DQB1*0301-DQA1*0501 (25.0%) followed by DRB1*0301-DQB1*02-DQA1*0501 (10%) and DRB1*0701- DQB1*02-DQA1*0201 (6.5%). Data presented in this study suggest that the Iranian population shares some HLA components with populations resident in eastern and southern European countries.     

Allele and haplotype frequencies at human leukocyte antigen class I and II genes in Venezuela's population

Population studies represent an integral part and link in understanding the complex chain of host-pathogen interactions, disease pathogenesis, and MHC gene polymorphisms. Genes of Mongoloid, Caucasoid, and Negroid populations have created a distinctive HLA genetic profile in the Venezuelan population. Our objective was to determine the predominant HLA class I and II alleles and haplotype frequencies in the hybrid population of Venezuela. The study population consisted of 486 healthy unrelated native Venezuelans and 180 families. We examined the frequency of HLA A-B-C, HLA-DQ and HLA-DR genes by polymerase chain reaction and subsequent hybridization with sequence-specific oligonucleotide probes. Phenotypic, allelic and haplotype frequencies were estimated by direct counting and using the maximum-likelihood method. The predominant HLA class I alleles were A*02, A*24, A*68, B*35, B*44, B*51, B*07, B*15 and Cw*07. Regarding HLA class II, the most frequent alleles were DQB1*03 and DRB1*04, DRB1*15, DRB1*13, DRB1*07. The prevailing haplotype was HLA-A*02B*35 DQB1*03 DRB1*04. Some of these alleles and haplotype frequencies were predominantly present in Amerindians (A*02, A*24, B*35, Cw*07, DRB1*04, A*24 B*35). Previous reports have shown high incidence of A*02, B*44, B*51, DRB1*15, DRB1*13, DRB1*07 alleles in several European populations and A*68, B*07, B*15 alleles in African Americans, which could have contributed to the ethnic admixture of the Venezuelan population. We conclude that our results provide strong evidence that Venezuela's population represents an admixture of the primitive Mongoloid Aborigines, Caucasoid Europeans and Western African Negroid migrants.     

High-resolution human leukocyte antigen allele and haplotype frequencies of the Polish population based on 20,653 stem cell donors

We present high-resolution allele and haplotype frequency (HF) estimations of the Polish population based on more than 20,000 registered stem cell donors. Sequencing-based donor human leukocyte antigen (HLA) typing led to unambiguous typing results in most cases (between 94.3% for HLA-DRB1 and 96.9% for HLA-B). HF estimations were carried out with a new, validated implementation of the expectation-maximization algorithm that allowed processing of data with ambiguities. Our results confirm several earlier results, for example, the relative commonness of the haplotype A*25:01 g, B*18:01 g, C*12:03, DRB1*04:01 in the Polish population. Because of the large sample size, we were able to obtain results of unprecedented accuracy. The estimated population-specific HFs were then used to analyze questions of strategic donor registry planning. Simulated matching probabilities by donor file size suggest that there is a need for intense donor recruitment efforts in Poland despite the large German donor registry and the genetic relatedness of both populations. Based on the current German registry size of approximately 4 million donors, the recruitment of 100,000 Polish donors would produce a stronger increase in matching probabilities for Polish patients than the recruitment of 3.3 million additional German donors.     

Estimation of high-resolution HLA-A, -B, -C, -DRB1 allele and haplotype frequencies based on 8862 German stem cell donors and implications for strategic donor registry planning

Human leukocyte antigen (HLA) haplotype frequency distributions in specific populations can be applied to optimize both individual stem cell donor searches and donor registry planning. We present allele and haplotype frequencies derived from a data set of 8862 German stem cell donors who were typed at high resolution for the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genes upon registration. Calculated haplotype frequencies were used to estimate the probability p to find matching donors subject to donor registry size n. The impact of various matching standards on p(n) was analyzed. When high-resolution matching for HLA-A, HLA-B, HLA-C, and HLA-DRB1 is required, p(1,000,000) is 0.678. The corresponding value for n = 7,000,000 is 0.859. In a scenario with low-resolution matching and no consideration of HLA-C, p(1,000,000) is 0.863 and thus larger than p(7,000,000) in the scenario with stricter matching requirements. As recent findings support the importance of high-resolution matching of HLA-A, HLA-B, HLA-C, and HLA-DRB1 for outcomes of hematopoietic stem cell transplantation, our results are highly relevant for strategic planning and resource allocation of donor centers and registries.     

HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo populations

Abstract: HLA class II alleles were identified in 181 healthy unrelated Ethiopian children of both sexes and in 350 European controls from the South of France. The Ethiopian individuals belonged to the two major ethnic groups of the country: Oromo ( N =83) and Amhara ( N =98). In both panels, genetic polymorphism of HLA class II alleles was analysed for the first time by molecular typing of DRB1, DQA1 and DQB1 loci. Allelic and phenotypic frequencies were compared with those of European controls and other African populations. Construction of HLA class II three-locus haplo-types was also performed. The study revealed some differences between the two groups. Characteristic features of Central and North African populations appeared on the Ethiopian HLA genotypes. Surprisingly, DRB1*11 presented one of the lowest gene frequencies in both Ethiopian ethnic groups in contrast to Europeans and West Africans. Furthermore, this decrease was more marked than those observed using serological techniques in other geographically close East African countries. Oromo and Amhara only showed minor differences in spite of their different origins and histories. One significant difference consisted of a lower DRB1*01 gene frequency in Oromo as reported in most West African people. Some new or rare haplotypes were also observed in the Oromo group. Our results underline the distinctive features of the Ethiopian populations among the few HLA genotyping data available for East African groups and emphasise the major interest of such investigations in this region of Africa.     

Human leukocyte antigen class I (A,B and C) allele and haplotype variation in a South African Indian population

In 2013, ～1,329,300 individuals made up the South African Indian population, which constituted ～2.5% of the total population of ～53 million. Historically, from 1860 to 1911, indentured labourers were imported from India, to work in the sugar-cane plantations in the KwaZulu-Natal Province. The local Indian community was further augmented by “passenger” immigrants who paid for passage to South Africa. Extensive HLA allelic variability exists in mainland Indian populations. We investigated HLA-A, -B and -C allele and haplotype diversity in 50 healthy, unrelated individuals recruited from the South African Indian population for comparison to data from mainland India.     

Characterization of the major histocompatibility complex class I chain-related gene B (MICB) polymorphism in a northern Chinese Han population: the identification of a new MICB allele, MICB*023

Major histocompatibility complex class I chain-related gene B (MICB) has only been characterized for allelic variation in very few human populations. The MICB polymorphism remains largely unknown in Chinese populations. In this study, 104 healthy unrelated Han subjects recruited from central Inner Mongolia Autonomous Region, northern China, were investigated by sequence-based typing for MICB allelic variation, the association of MICB alleles with AluyMICB insertion/deletion dimorphism located in MICB intron 1, linkage disequilibrium of MICB with human leukocyte antigen (HLA)-B and MICA, and HLA-A-C-B-MICA-MICB haplotypic diversity. Ten kinds of MICB alleles were observed, among which MICB*005:02/010, MICB*002:01, and MICB*004:01 were the most frequent alleles with frequencies of 51.44, 16.35, and 11.54%, respectively. Significant linkage disequilibrium (LD) was observed for 9 of the 21 HLA-B-MICB haplotypes and 6 of the 17 MICA-MICB haplotypes with a frequency >1.5%. In particular, HLA-B*13:01 and HLA-B*13:02, both of which were frequently represented in this population, exhibited a distinct LD pattern with the MICB allele. A new MICB allele, MICB*023, was identified, which differed from MICB*005:02/010 by a single mutation of G to A at position 86 in exon 2, resulting in an amino acid change from arginine to histidine at codon 6. HLA-A*30-C*06-B*13:02-MICA*008:01-MICB*005:02/010 was the most common haplotype, with a frequency of 8.64% in this population. HLA-A*02-C*08-B*48-MICA*Del-MICB*009N demonstrated a frequency of 2.4% in this population. Our results provide for the first time data regarding the MICB genetic polymorphism in northern Chinese Han populations and will form the basis for future studies of the potential role of MICB in allogeneic organ transplantation and disease association in related ethnic groups.     

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.     

Human leukocyte antigen class I (A,B and C) allele and haplotype variation in a South African Mixed ancestry population

South Africa has a large (∼53 million), ethnically diverse population (black African, Caucasian, Indian/Asian and Mixed ancestry) and a high disease burden (particularly HIV-1 and Mycobacterium tuberculosis). The Mixed ancestry population constitutes ∼9% of the total population and was established ∼365 years ago in the Western Cape region through interracial mixing of black Africans, Europeans and Asians. Admixed populations present unique opportunities to identify genetic factors involved in disease susceptibility. Since HLA genes are important mediators of host immunity, we investigated HLA-A, -B and -C allele and haplotype diversity in 50 healthy, unrelated individuals recruited from the Mixed ancestry population.     

HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies distinguish Eastern European Americans from the general European American population

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 558 consecutively recruited US volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of 31 HLA-A alleles, 29 HLA-C alleles, 59 HLA-B alleles, and 42 HLA-DRB1 alleles identified (A*0325, B*440204, Cw*0332, and *0732N) are novel. The HLA-A*02010101g allele was observed at a frequency of 0.28. Two-, three-, and four-locus haplotypes were estimated using the expectation-maximization algorithm. The highest frequency extended haplotypes (A*010101g–Cw*070101g–B*0801g–DRB1*0301 and A*03010101g–Cw*0702–B*0702–DRB1*1501) were observed at frequencies of 0.04 and 0.03, respectively. Linkage disequilibrium values (     ) of the constituent two-locus haplotypes were highly significant for both extended haplotypes ( P values were less than 8 × 10⁻¹⁰) but were consistently higher for the more frequent haplotype. Balancing selection was inferred to be acting on all the four loci, with the strongest evidence of balancing selection observed for the HLA-C locus. Comparisons of the A–C–B haplotypes and DRB1 frequencies in this population with those for African, European, and western Asian populations showed high degrees of identity with Czech, Polish, and Slovenian populations and significant differences from the general European American population.     

HLA allele and haplotype frequencies in the Panamanian population

In this study, we report for the first time HLA allele and haplotype frequencies in the modern Panamanian population at a two-field (four digits) resolution level. Reported frequencies were calculated from genotype data for the HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 loci of 462 healthy unrelated Panamanian adults of Hispanic ethnicity. In addition to providing new insights on the allelic structure of the Panamanian population and its origin, these data are critical for better planning of healthcare strategies in the country and for future research exploring the association with certain chronic and infectious diseases.     

Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population

HLA class I and class II allelic genotypes were determined in 371 unrelated individuals and 309 members of 81 families inhabiting the central Japan area. A total of 20 HLA-A alleles, 16 HLA-Cw alleles, 38 HLA-B alleles, 27 HLA-DRB1 alleles, 15 HLA-DQB1 alleles and 12 HLA-DPB1 alleles were detected. By the two-, three-, four-, five- and six-locus allelic association analyses extracted from the HLA-A to -DPB1 locus, 26 HLA-Cw-B haplotypes, 25 HLA-DRB1-DQB1 haplotypes, 42 HLA-Cw-B-DRB1 haplotypes, 37 HLA-Cw-B-DRB1-DQB1 haplotypes, 29 HLA-A-Cw-B-DRB1-DQB1 haplotypes and 21 HLA-A-Cw-B-DRB1-DQB1-DPB1 haplotypes with the frequencies of higher than 0.005 were recognized. Among 19 HLA-B alleles with the high allele frequencies (above 0.007), 9 HLA-B alleles, B*0702, B*1301, B*3701, B*3901, B*4006, B*4403, B*5201, B*5901 and B*6701 were found to be tightly associated with single HLA-Cw alleles. Most of HLA-DRB1 alleles showed strong associations with single HLA-DQB1 alleles, but DRB1*0802 and DRB1*1401 were associated with two different DQB1 alleles. Extended haplotypes carrying infrequent class I alleles with the allele frequencies of lower than 0.007 were defined by family studies. Gene frequencies and haplotypic associations within the entire HLA classical loci elucidated at the high resolution (four-digital) allelic level will provide useful information on anthropology, marrow donor registry, legal medicine and disease-association studies.     

The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations

The Caucasus and the Iberian peninsula have been connected from a linguistic (Basque and Kvartelian languages), toponimic and historic perspectives. They also represent places (e.g. Dmanisi in Georgia and Atapuerca in Northern Spain) where the oldest hominoid remains in Europe are being discovered and studied. These circumstances prompted us to study the genetic background of the Svans (living on the southern slopes of the Greater Caucasus in the Republic of Georgia) in comparison with Basques from the semi-isolated Arratia valley as well with other Northern Spanish and Western European populations. DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*1301-DQA1*0103-DQB1*0603 haplotypes were found in Svans at the highest frequency. The second most frequent three-locus haplotypes in this population were DRB1*0701-DQA1*0201-DQB1*0201 and DRB1*1301-DQA1*0103-DQB1*0602. Furthermore, the following 5-locus extended haplotypes were not found in other populations: A3-B8-DRB1*11-DQA1*0501-DQB1*0301, A2-B8-DRB1*13-DQA1*0103-DQB1*0603, A2-B40-DRB1*14-DQA1*0104-DQB1*0501, A2-B51-DRB1*08-DQA1*0401-DQB1*0402, A3-B7-DRB1*03-DQA1*0501-DQB1*0201 and A24-B39-DRB1*08-DQA1*0401-DQB1*0402. Other haplotypes present in Svans were also frequently observed in Northern Spain and in other Western European countries. However, haplotypes reported as characteristic for Basques were not found in the Svans. A dendrogram using HLA class II alleles places the closest genetic distance observed between Svans and Czechs, whereas Slovenes and other Mediterranean populations (Jews, Hungarians, Frenchmen, Sardinians and Greeks) have the greatest genetic distance. When both HLA class I and class II alleles from 17 populations were compared, the smallest genetic distances were with Rumanians, Czechs and Armenians. Northern Spanish populations were placed closer to each other and clearly separated from Svans. In conclusion, the Svan population shows considerable polymorphism. These observations suggest a mixture of alleles in Svans from geographically distinct areas, and probably do not support a common ancestor for these Caucasian inhabitants and people from Northern Spain.     

HLA class I and class II allele distribution in the Peruvian population

The distribution of HLA-A, -B, -C, -DRB1 and -DQB1 alleles in the Peruvian population was studied and compared with those of other populations in order to provide further information about their anthropological origin. Our data are consistent with the Mestizo character of this population. In terms of genetic distance Peruvians are closest to Bolivians, which is in agreement with the geographical location and the cultural and anthropological background of the two human groups. Several HLA-B alleles originally described in genetically isolated Amerindian tribes are also present in the sample studied here. This fact and the reported finding of these alleles in several Amerindian groups suggests that they were present in the first wave of humans that populated South America (Paleoindians) before they split to give rise to the different South American tribes.     

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.     

HLA class I allele lineages and haplotype frequencies in Arabs of the United Arab Emirates

The high degree of polymorphism of the HLA system provides suitable genetic markers to study the diversity and migration of different world populations and is beneficial for forensic identification, anthropology, transplantation and disease associations. Although the United Arab Emirates (UAE) population of about nine million people is heterogeneous, information is limited for the HLA class I allele and haplotype frequencies of the Bedouin ethnic group. We performed low‐resolution PCR‐SSP genotyping of three HLA class I loci at HLA‐A, ‐B and ‐C for 95 unrelated healthy Bedouins from the cities of Al Ain and Abu Dhabi in the UAE. A total of 54 HLA allele lineages were detected; the most frequent low‐resolution allele lineages at each HLA locus were A*02 (0.268), B*51 (0.163) and C*07 (0.216). The inferred estimates for the two most frequent HLA‐A and HLA‐B haplotypes were HLA‐A*02 ~ HLA‐B*50 (0.070) and HLA‐A*02 ~ HLA‐B*51 (0.051), and the most frequent 3‐locus haplotype was HLA‐A*02 ~ HLA‐B*50 ~ HLA‐C*06 (0.068). The HLA allele lineage frequencies of the UAE Arabs were compared to those previously reported for 70 other world populations, and a strong genetic similarity was detected between the UAE Arabs and the Saudi Arabians from the west with evidence of a limited gene flow between the UAE Arabs and Pakistani across the Gulf from the east, and the UAE Arabs and Omani from the south of the Gulf Peninsula.     

The distribution of human leukocyte antigen-A, -B,and -DRB1 alleles and haplotypes based on high-resolution genotyping of 167 families from Jiangsu Province,China

We investigated the human leukocyte antigen (HLA)-A, -B, and -DRB1 allele frequencies, the A–B–DRB1, A–B, B–DRB1, and A–DRB1 haplotype frequencies, and the characteristics of linkage disequilibrium between 2 loci in high resolution based on 167 unrelated families from Jiangsu Province, China. A total of 26 alleles at the A locus, 55 alleles at the B locus, and 34 alleles at the DRB1 locus were reported in this study. The top 5 most frequent HLA alleles at the HLA-A, -B, and -DRB1 loci, respectively, were A*11:01, A*24:02, A*02:01, A*33:03, A*30:01; B*13:02, B*40:01 B*46:01, B*58:01, B*54:01; DRB1*09:01, DRB1*07:01, DRB1*12:02, DRB1*15:01, and DRB1*08:03. Several haplotypes with high frequencies were deduced in this study. The top 3 most common A–B–DRB1 haplotypes observed were A*30:01–B*13:02–DRB1*07:01, A*33:03–B*58:01–DRB1*03:01, and A*02:07–B*46:01–DRB1*09:01. The top 3 most common A–B haplotypes were A*30:01–B*13:02, A*33:03–B*58:01, and A*02:07–B*46:01. The top 4 most common A–DRB1 haplotypes were A*30:01–DRB1*07:01, A*33:03–DRB1*13:02, A*24:02–DRB1*09:01, and A*33:03–DRB1*03:01. Finally, the top 3 most common B–DRB1 haplotypes were B*13:02–DRB1*07:01, B*46:01–DRB1*09:01, and B*58:01–DRB1*03:01. From the linkage disequilibrium calculation, the most prominent associations were A*30:01–B*13:02, B*13:02–DRB1*07:01, and A*01:03–DRB1*01:02. These allele and haplotype frequencies could be useful for finding the best matched donors for patients in the China Marrow Donor Program Jiangsu Branch.     

HLA-DR, DQ nucleotide sequence polymorphisms in the Pasiegos (Pas valleys, Northern Spain) and comparison of the allelic and haplotypic frequencies with those of other European populations

In general, Northern Spain has remained geographically isolated from neighboring Spanish regions for centuries: steep mountains create small isolated and inbred population groups with their own characteristic cultures and unique gene pools. The Pasiego region forms an area of distinctive characteristics among the people living in Northern Spain, although the origin of the inhabitants of the Pas valleys (Pasiegos) is not clearly defined. We have studied the MHC class II alleles in a large sample of unrelated individuals living in the Pas valleys. Allelic and haplotypic frequencies, population distances and their corresponding dendrogram, using the N-J method, were used to study the relationships between populations. The closest is observed between Pasiegos and Danes, followed by other European people in the following decreasing order: Poles, Germans, non-Pasiego Cantabrians, Belgians, Basques, French, other Spaniards from Madrid, Italians, Finns, Croatians, Welsh, Ashkenazi Jews and other Mediterranean populations (Greeks, Hungarians, Sardinians and Bulgarians). Particular characteristic Northern European alleles are observed with high frequency in the Pasiegos and non-Pasiego Cantabrians (DRB1*1501-DQA1*0102-DQB1*0602). The second most frequent three-locus haplotype in both populations is DRB1*0701-DQA1*0201-DQB1*0201. These observations suggest an important mixture of alleles from geographically distinct areas. In conclusion, the Pasiegos are typical examples of isolated genetic pools in the Iberian Peninsula and allow one to suggest that what we call the "Pasiego cluster" can be considered, in many ways, as another example of the few deviant groups (e.g. Lapps, Basques and Sardinians) having preserved their genetic, social and ethnographic characteristics and, in some cases, their ancestral language.