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.     

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.     

Genetic link between Asians and native Americans: evidence from HLA genes and haplotypes.

We have been studying polymorphisms of HLA class I and II genes in East Asians including Buryat in Siberia, Mongolian, Han Chinese, Man Chinese, Korean Chinese, South Korean, and Taiwan indigenous populations in collaboration with many Asian scientists. Regional populations in Japan, Hondo-Japanese, Ryukyuan, and Ainu, were also studied. HLA-A, -B, and -DRB1 gene frequencies were subjected to the correspondence analysis and calculation of DA distances. The correspondence analysis demonstrated several major clusters of human populations in the world. "Mongoloid" populations were highly diversified, in which several clusters such as Northeast Asians, Southeast Asians, Oceanians, and Native Americans were observed. Interestingly, an indigenous population in North Japan, Ainu, was placed relatively close to Native Americans in the correspondence analysis. Distribution of particular HLA-A, -B, -DRB1 alleles and haplotypes was also analyzed in relation to migration and dispersal routes of ancestral populations. A number of alleles and haplotypes showed characteristic patterns of regional distribution. For example, B39-HR5-DQ7 (B*3901-DRB1*1406-DQB1*0301) was shared by Ainu and Native Americans. A24-Cw8-B48 was commonly observed in Taiwan indigenous populations, Maori in New Zealand, Orochon in Northeast China, Inuit, and Tlingit. These findings further support the genetic link between East Asians and Native Americans. We have proposed that various ancestral populations in East Asia, marked by different HLA haplotypes, had migrated and dispersed through multiple routes. Moreover, relatively small genetic distances and the sharing of several HLA haplotypes between Ainu and Native Americans suggest that these populations are descendants of some Upper Paleolithic populations of East Asia.     

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.     

HLA molecular markers in Tuvinians: a population with both Oriental and Caucasoid characteristics

HLA class I and class II alleles have been studied for the first time in the Turkish-speaking Tuvinian population, which lives in Russia, North of Mongolia and close to the Altai mountains. Comparisons have been done with about 11000 chromosomes from other worldwide populations, and extended haplotypes, genetic distances, neighbor joining dendrograms and correspondence analyses have been calculated. Tuvinians show an admixture of Mongoloid and Caucasoid characters, the latter probably coming from the ancient Kyrgyz background or, less feasibly, more recent Russian Caucasoid admixture. However, Siberian population traits are not found and thus Tuvinians are closer to Central Asian populations. Siberians are more related to Na-Dene and Eskimo American Indians; Amerindians (from nowadays Iberian–America) are not related to any other group, including Pacific Islanders, Siberians or other American Indians. The 'more than one wave' model for the peopling of the Americas is supported.     

Origin of Mexican Nahuas (Aztecs) according to HLA genes and their relationships with worldwide populations

A Nahua Aztec isolated group from Morelos State (Mexico) was studied for their HLA profile. The relationship with other Amerindians and worldwide populations was studied by using 13,818 chromosomes and calculating Nei's chord genetic distances (DA), neighbor-joining dendrograms and correspondence multidimensional values. Three new HLA extended haplotypes were found in our group: A*30-B*49-DRB1*1001-DQB1*0501 (the most frequent one in this population), A*02-B*52-DRB1*1402-DQB1*0301 and A*68-B*61-DRB1*1602-DQB1*0303. Both genetic distances and correspondence analyses clearly show that our Nahua isolated group is genetically close to some of the most ancient groups living in Mexico (Mayans, Zapotecans, Mixtecans). This suggests that Nahua language (Nahuatl) may have been imposed to scattered groups throughout Mexico; otherwise Aztecs may have been living in Mexico long before their postulated immigration in the XII century AD.     

IMMUNOGENETIC ANALYSIS OF HLA-DR10 HOMOZYGOUS INDIVIDUALS

Molecular, cellular and serological analysis of Major Histocompatibility Complex alleles was performed on three individuals who appeared to be HLA-DR10 homozygous by DNA restriction fragment analysis. Each donor was of different ethnic origin: Caucasoid, Asian Indian and African Negroid. The results of our studies show that the Caucasoid and Asian donors are indeed homozygous for the HLA-DR 10 allele, while the African donor also possesses the DRB1*0103 allele. Homozygosity for the HLA-A1B37-Cw6-DR10-DQ5 haplotype in the Caucasoid donor was confirmed by familial segregation analysis. The B-lymphoblastoid cell line produced from this donor should prove useful in studies of HLA immunogenetics.     

HLA-A, -B, -DR and -DQ allele and haplotype frequencies in the Moroccan population: a general population study

PURPOSE OF STUDY: The aim of this general population study is to extend our knowledge about the HLA-A, -B, -DR and -DQ genes distribution and their diversity among the Moroccan population. PATIENTS AND METHODS: One hundred and ten unrelated healthy Moroccans from diverse regions of the country were included in the study. HLA typing was done either by serological (standard complement dependent microlymphocytotoxicity) and/or molecular (sequence-specific primer amplification) techniques. RESULTS: The most frequent alleles observed were: HLA-A2 (19.1%), -A1 (10%), -A3 (10%), -B44 (9.6%), -DR3 (17.1%), -DR4 (15.3%), -DQ2 (30.6%), -DQ6 (26.4%) and -DQ3 (25%). No predominant haplotype was observed for HLA A-B while high frequency was observed for some HLA DR-DQ associations (DR3-DQ2, DR15-DQ6, DR7-DQ2, DR4-DQ3, DR13-DQ6). Comparison with neighbouring populations, on the basis of alleles, haplotypes and genetic distances, showed that Moroccan population is close to the Algerians, the Tunisians, the Spaniards and the French. The haplotype frequencies revealed also relationships with Italians, Sardinians, Basques, Portuguese and Moroccan Jews populations. CONCLUSION: Our results confirm and extend the current knowledge about the Moroccan genetic pattern and reflect all the ethnic diversity of the country. This study will be helpful in the future for clinical analysis like transplantation and HLA-associated diseases in Moroccan population.     

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.     

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.     

The contribution of the HLA-A, -B, -C and -DR, -DQ DNA typing to the study of the origins of Spaniards and Basques

Abstract: The high polymorphism of the HLA system has been used as a powerful genetic tool to single out individuals and populations. By studying characteristic allele frequencies and extended HLA haplotypes in different populations, it is possible to identify ethnic groups and establish the genetic relationships among them. In the present study, HLA-A, -B, -C, -DR and -DQ typing at the serological/antigenic and the DNA level has been used for the first time to assign specific HLA frequencies and haplotypes to Spaniards and Basques and compare them with frequencies in other populations, particularly with North Africans. Allelic frequencies do not significantly differ between Spaniards and Basques. HLA genetic distances and their respective dendrogram together with the results on complete HLA haplotypes place Basques and Spaniards closer to paleo-North African populations than to other Europeans. This goes in favour of the Basques being a relative genetic isolate coming from the primitive Iberian/paleo-North African people. In addition, a tentative assignment of the most common Spanish HLA haplotypes to the different people who populated Iberia according to historical records has been done.     

HLA genes in Wayu Amerindians from Colombia

Amerindians origins and prehistory are still debated. HLA profile is different to all other World populations, although they have particular alleles in common with Asians, Australians and Pacific Islanders. In the present work, HLA-A, -B, -DRB1, -DQB1 alleles have been studied in Wayu Amerindians from Colombia. HLA alleles haplotypes, genetic distances and NJ dendrograms were calculated by Arlequin and DISPAN software. Only a few both class I and class II alleles have been observed. Most common extended haplotypes include: A*24-B*51-DRB1*0403-DQB1*0302, A*2-B*15-DRB1*1602-DQB1*0301, A*2-B*35-DRB1*0407-DQB1*0302, but also A*68-B*15-DRB1*0403-DQB1*0302. No trace of Caucasoid or Negroid admixture is detected. The Wayu HLA profile is typical from Amerindians and shows how languages and genes do not correlated particularly in this case (i.e., Wayu closest HLA genetic group is North Argentinian Guarani group). Results obtained in this work may be useful for future transplant programs and also for HLA linked diseases and individualized pharmacogenetics.     

HLA genes in Wayu Amerindians from Colombia

Amerindians origins and prehistory are still debated. HLA profile is different to all other World populations, although they have particular alleles in common with Asians, Australians and Pacific Islanders. In the present work, HLA-A, -B, -DRB1, -DQB1 alleles have been studied in Wayu Amerindians from Colombia. HLA alleles haplotypes, genetic distances and NJ dendrograms were calculated by Arlequin and DISPAN software. Only a few both class I and class II alleles have been observed. Most common extended haplotypes include: A*24-B*51-DRB1*0403-DQB1*0302, A*2-B*15-DRB1*1602-DQB1*0301, A*2-B*35-DRB1*0407-DQB1*0302, but also A*68-B*15-DRB1*0403-DQB1*0302. No trace of Caucasoid or Negroid admixture is detected. The Wayu HLA profile is typical from Amerindians and shows how languages and genes do not correlated particularly in this case (i.e., Wayu closest HLA genetic group is North Argentinian Guarani group). Results obtained in this work may be useful for future transplant programs and also for HLA linked diseases and individualized pharmacogenetics.     

Autoimmune-associated HLA-B8-DR3 haplotypes in Asian Indians are unique in C4 complement gene copy numbers and HSP-2 1267A/G

The classical AH8.1 (HLA-A1-B8-DR3-DQ2) is the most common Caucasian haplotype, associated with several autoimmune diseases, immunologic hyperreactivity and rapid progression to the acquired immunodeficiency syndrome. However, in Asian Indians, there are multiple unique B8-DR3 haplotypes that are associated with autoimmunity and differ significantly from the common Caucasian AH8.1. The Indian HLA-A1-B8-DR3 is therefore referred to as an AH8.1 variant. The aims of this study were to compare C4A and C4B copy numbers and to identify alleles in HSP70-2 and LTA in these haplotypes. The Indian B8-DR3 haplotypes differ from the Caucasian AH8.1 at C4A and HSP70-2 loci. The Indian B8-DR3 haplotypes have 1 copy each at C4A and C4B, while the Caucasian AH8.1 has 1 copy at C4B but no C4A gene. Moreover, the Indian and Caucasian B8-DR3 haplotypes had HSP70-2 1267 (*)A, and *G alleles, respectively. By contrast, the LTA 252 *G allele occurred both in the Indian and Caucasian haplotypes. The Indian haplotypes also contained Bf*F and TNF-308*G that were different from the Caucasian equivalents Bf*S and TNF-308*A. These differences and previous studies support the hypothesis that B8-DR3-DQ2 haplotypes in Asian Indian population might have originated independently of Caucasian AH8.1 selectively through recombination and mutations. Because autoimmune disease associations are shared among these otherwise diverse haplotypes, these data strongly suggest that some shared component(s) of all these associated haplotypes may be playing a key role in such associations.     

Gorgan (Turkmen in Iran) HLA genetics: transplantation,pharmacogenomics and anthropology

HLA class I and II alleles have been studied in a population from Gorgan (North East Iranian city bordering Turkmenistan). This population is composed of mainly Turkmen who speak Oghuz Turkish language. Comparison of Gorgan people HLA profile has been carried out with about 7984 HLA chromosomes from other worldwide populations; extended haplotypes and three dimension genetic distances have been calculated by using neighbor-joining and correspondence relatedness analyses. Most frequent extended HLA haplotypes show a Siberian/Mediterranean admixture and closest populations are Chuvashians (North Caspian Sea, Russia) and other geographically close populations like Siberian Mansi, Buryats and other Iranians. New extended HLA haplotypes have been found, such as: A*31:01-B*35:01-DRB1*15:01-DQB1*03:01, A*01:01-B*35:01-DRB1*03:01-DQB1*02:01. Relationships of Turkmen with Kurgan (Gorgan) archaeological mounds, Scythians and Sarmatians are discussed. This study is also useful for a future transplantation Gorgan waiting list, Gorgan HLA and disease epidemiology and HLA pharmacogenomics.     

Selective co-evolution of the D6STNFa microsatellite region with HLA class I and II loci

Abstract: We analyzed the HLA-A, -B, -DR and -DQ phenotypes and 12 microsatellite locus genotypes within and close to the major histocompatibility complex in a panel of 98 randomly selected, healthy, unrelated Dutch Caucasoid individuals. Allele frequencies and Hardy-Weinberg equilibrium (HWE) were calculated. Also, the linkage disequilibrium patterns between HLA and microsatellite loci were studied. The HLA-A, -B, -DR, -DQ and six microsatellite loci centromeric of the HLA-A showed HWE. In contrast, all microsatellites telomeric of the HLA-A showed deviation from HWE due to excess of homozygosity. Linkage disequilibrium analyses provided strong evidence that among the tested microsatellite loci only the alleles of the D6STNFa locus are in linkage disequilibrium with both HLA-B and -DR. Our results suggest that selection acting on the HLA genes includes the D6STNFa locus and linked genes.     

HLA polymorphism in the Murcia population (Spain): in the cradle of the archaeologic Iberians.

Human leukocyte antigen (HLA) study in Murcian individuals was performed in order to provide information of their historical origins and relationships with other Iberian and Mediterranean populations. HLA class I and class II alleles were determined in 173 unrelated Caucasoid donors from Murcia Region in the Southeast of Spain by serologic and DNA based polymerase chain reaction (PCR) typing. Class I antigen and class II allele frequencies of our series were not very different to those found in Spaniards. The analysis of extended haplotypes showed that the three haplotypes most frequent in our population were respectively, A29-B44-Cwb-DRB1*0701-DRB4*0101-DQA1*0201-DQB1*0202, A1-B8-Cw7-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201 and A30-B18-Cw5-DRB1*0301-DRB3*0101-DQA1*0501-DQB1*0201. They were followed by A26-B38-Cwb-DRB1*1301-DRB3*0202-DQA1*0103-DQB1*0603, which could point to an ancestral relationship between Murcian and Portuguese Iberian populations, and by A2-B7-Cw7-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 also present in all Iberian Peninsula populations. Allelic frequencies, populations distance dendrogram and correspondence analysis were used to study the relationships between Murcian and other populations. The closest relation was observed with Spaniards and Portuguese, followed in decreasing order by French, Italians, Algerians, Germans, Catalans, Basques, Cretans, Sardinians, and Greeks. Thus, Murcian population seems to belong to the European genetic pool, revealing a lesser genetic distance with the North Africans and the rest of populations from the Iberian Peninsula.     

HLA class I and II polymorphisms in Azores show different settlements in Oriental and Central islands

Human leucocyte antigen-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 polymorphisms were examined in the Azorean population. The data were obtained at high-resolution level, using polymerase chain reaction (PCR) with sequence-specific primer, PCR-sequence-specific oligonucleotides and sequence-based typing. The most frequent allele in each locus was: A*0201 (24.5%), B*510101 (9.8%), Cw*0401 (14.8%), DRB1*070101 (18.3%), DQA1*0201 (17.4%) and DQB1*0301 (19.4%). The predominant extended haplotype was A*0202-B*1503-Cw*0202-DRB1*090102-DQA1*0303- DQB1*0202 (1.9%), which was found to be absent in the Portuguese mainland. The present study corroborates historical sources that say the Azores were populated not only by Portuguese but also by other Europeans, mostly Flemish people. Despite dendrogram analysis showing some remote Asian genetic affinities, the lack of specific alleles and haplotypes from those populations does not allow us to conclude for direct influence. Haplotype and allele frequencies in Azores show no homogeneous distribution between Oriental and Central islands of this archipelago. The Oriental islands harbour several haplotypes already found in mainland Portugal and identified as Mediterranean and European. The Central group of islands on the contrary clearly shows an influence of north Europeans (most probably derived from a well-documented Flemish settlement), with much less affinity to mainland Portugal.     

Human leukocyte antigen-A, -B and -C alleles and human leukocyte antigen haplotypes in Turkey: relationship to other populations

In this study, we present, for the first time, human leukocyte antigen (HLA) class I allele and haplotype frequencies at the DNA level in a sample of 142 donors from Turkey. HLA typing was performed by medium-to-high resolution polymerase chain reaction sequence-specific oligonucleotide probes method. The most frequent HLA alleles at class I locus were A*0201(0.257), -B*35(0.204) and -Cw*04(0.173). A*0201-B*35-Cw*04(0.056) was the most common three-locus haplotype. Allele and haplotype frequency comparisons and neighbour-joining dendrograms, constructed using DA genetic distances and correspondence analysis using HLA-A, -B and -C, and -DRB1 allele frequencies, revealed similarities with other Mediterranean and European populations, but not with Mongol populations. These results agree with previous studies and confirm that the present day Turkish population is genetically more similar to its geographic neighbours than its historical neighbours in central Asia. The comprehensive HLA data on the Turkish population at the DNA level including up to six-locus putative haplotypes generated in this study will be useful for further studies.     

Human platelet antigens: typing by PCR using sequence-specific primers and their distribution in blood donors resident in Wales.

We developed and validated HPA-1 to HPA-6 typing by PCR-SSP using a combination of established, modified and newly designed sequence-specific primers. We confirmed that the PCR primer mixtures functioned under the same PCR conditions as our standard HLA-A, -B, -C, -DR, -DQ PCR-SSP typing system. This allows concurrent testing for both HPA and HLA specificities and is therefore the system of choice for both clinical and large-scale blood donor panel HPA and HLA typing by PCR-SSP. Test validation included typing a population of blood donors living in Wales. These HPA frequencies were consistent with those of other European Caucasoid populations. HPA-4b and -6b were absent and HPA-5b, which shows some frequency variation, had a phenotype frequency of 18.9% (allele frequency 0. 0973), being close to that of the Dutch (19.7%) and Austrian (20.4%) populations and almost twice that found in Finns (10.0%). HPA genotype frequencies showed a good fit to Hardy-Weinberg equilibrium, further supporting the validity of our typing method.