DQA1 and DQB1 promoter diversity and linkage disequilibrium with class II haplotypes in Mexican Mestizo population

The upstream sequences in the 5' flanking region of HLA class II genes, regulate their expression and contribute to the development of immunological diseases. We analyzed 105 healthy unrelated Mexican Mestizos for QAP and QBP polymorphism. DNA typing for DRB1, DQA1, DQB1, QAP1 and QBP1 was done using a standardized PCR-SSOP. Although all QAP alleles previously described were found in Mexicans, the distribution differed as compared to other populations. QAP-3.1, 4.1 and 4.2 were the most frequent alleles and were associated with DQA1*03, *0501 and *0402 respectively. The prevalent QBP alleles were 3.21, 3.1 and 4.1 found mainly associated with DQB1*0302, *0301 and *0501. Linkage disequilibria between the promoter and the corresponding DQA1 and DQB1 allele, are in general the same as described by others. A total of 61 different haplotypes were defined, only six of them with a frequency above 4%. The haplotypes DRB1*0407-QAP-3.1-DQA1*03-QBP-3.21-DQB1*0302 (HF = 14.37%) and DRB1*0802-QAP-4.2-DQA1*0401-QBP-4.1-DQB1*0402 (HF = 14.22%), which have an Amerindian ancestry, are the most frequent in Mexicans. Some rare combinations were detected such as DRB1*0405-QAP-1.3-DQA1*0101/4-QBP-5.11/5.12-DQB1*0501 and DRB1*0403-QAP-3.2-DQA1*03-QBP-3.21-DQB1*0302, probably due to ancient recombination events. This knowledge is relevant as a basis to evaluate functional implications and to explore the role of promoter diversity in disease expression.     

QAP and QPB polymorphism in Mexican mestizos and Indians

Although the sequences of the class II promoters are highly conserved, diversity has been found in the URRs of DR and DQ loci. For the promoter region of DQA1, 10 QAP alleles are defined and 12 QBP for DQB1 region; DNA of 46 Mexican Mestizos and 101 Seri Indians was typed for QAP, QBP and class II alleles using the PCR-SSO protocols of the 12th W, as part of the promoter component chaired by E. Albert. PCR-SSP was done to distinguish between QBP6.2 and 6.3. In both groups, all QAP alleles previously described were detected, excepting for 3.2, absent because the associated DQA1^*0302 is also lacking. One unusual haplotype accounting for 16.3% was observed: DRB1 ^*0802-QAP4.2-DQA1^*0401-DQB1^*0402-QBP4.1. QBP3.22 described in Whites, was not present in this haplotype. Neither QBP4.1 that associates with DQB1 ^*0401, or the latter have been found in Mexicans. A recombination possibly occured in the DQB1 region of an ancestral haplotype carrying QBP4.1. In Seri Indians, only 8 haplotypes were detected. Of these, 3 seem to be the ancestral ones: ^*0407-^*03011-3.1-^*0302-3.21; ^*0802-4.2-^*0401-^*0402-4.1; and ^*1402-4.1-^*0501-^*0301-3.1. The frequencies of 43.5%, 36.6% and 13.9% accounting for 94% of the haplotypes, indicate from an evolutionary viewpoint, that these originated from Orientals and probably conferred a great biological advantage. They are also the prevalent haplotypes in Mestizos (60.9%). One unusual QBP4.1 combination was detected in 2 Seris with DRB1^*0407-DQB1^*0302. The functional role of these variants in expression and in development of disease, must be explored.     

HLA class IIDRB, DQA1 and DQB1 polymorphisms in the Polish population from Wielkopolska

HLA DRB1, DQA1 and DQB1 alleles were determined by DNA PCR-SSO typing in a sample of 99 individuals originating from Wielkopolska (midwestern Poland). A high number of alleles (38 DRB1, 8 DQA1 and 14 DQB1) was detected at each locus, many of them presenting notable frequencies in this population. The three HLA loci are thus characterized by very high heterozygosity levels (93% for DRB1, 85% for DQA1, and 88% for DQB1), which confirms the results found for other European populations. A total of 6 DRB1-DQA1-DQB1 haplotypes are detected with an estimated frequency higher than 5%, namely, DRB1*1501-DQA1*0102-DQB1*0602, DRB1*0701-DQA1*0201-DQB1*0201, DRB1*0101-DQA1*0101-DQB1*0501, DRB1*1101-DQA1*0501-DQB1*0301, DRB1*03011-DQA1*0501-DQB1*0201, and DRB1*1301-DQA1*0103-DQB1*0603. A genetic distance analysis between the Polish and other world populations tested for HLA class II indicates that the Wielkopolska community is close to geographically close, rather than linguistically related populations from Europe. More generally, a good agreement between genetics and geography is found for DRB1 and DQB1 polymorphisms in Europe, suggesting that these two loci are highly informative for assessing historical relationships among humans.     

Distribution of HLA Class II Alleles and Haplotypes in Mexican Mestizo Population: Comparison with Other Populations

We describe the analysis of the Major Histocompatibility Complex (MHC) class II polymorphism in Mexican Mestizo population. The study provides the HLA-DRB1, DQA1 and DQB1 allele frequencies in 99 Mexican Mestizos. DNA from these individuals was typed by PCR followed by hybridization using sequence specific oligonucleotides (PCR-SSO). The relationship with other worldwide populations was studied by using HLA data from 69 different populations and calculating neighbor-joining dendrograms and correspondence multidimensional values. The highest frequencies were for DRB1*0802 (allele frequency = 0.151), DRB1*0701 (allele frequency = 0.111) and DRB1*0407 (allele frequency = 0.106). Among the eight DQA1 alleles detected, the most frequent were DQA1*03011 (allele frequency = 0.257), DQA1*0501 (allele frequency = 0.227) and DQA1*0401 (allele frequency = 0.166). Twelve DQB1 alleles were found and four of them, DQB1*0302 (allele frequency = 0.237), DQB1*0301 (allele frequency = 0.176), DQB1*0201 (allele frequency = 0.166) and DQB1*0402 (allele frequency = 0.166) showed the highest frequencies. The haplotype DRB1*0802-DQA1*0401-DQB1*0402 (0.151) predominated clearly, followed by DRB1*0701-DQA1*0201-DQB1*0201 (0.111) and DRB1*0407-DQA1*03011-DQB1*0302 (0.101). Both genetic distances and correspondence analyses showed that Mexicans clustered with Amerindian population. These results suggest that the Mexican Mestizo population be principally characterized by haplotypes presents in Amerindian and Caucasian populations with a low frequency of Black haplotypes. In summary, the HLA class II haplotype frequencies demonstrated the tri-racial component existing in Mexican Mestizos.     

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   

HLA-DRB1, DQA1 and DQB1 DNA polymorphisms in healthy Algerian and genetic relationships with other populations

Abstract: This study presents the results of HLA-DRB1, -DQA1, and -DQB1 sequence-specific oligonucleotide probe (SSOP) typings for a population sample of 47 individuals originating from Western Algeria. Allele and haplotype frequencies, as well as linkage disequilibria are computed by the standard methods used for the XIth International Histocompatibility Workshop data. A total of 24 alleles are detected at the DRB1 locus, where a very high heterozygosity level (0.914) is found. The highest DRB1 frequencies are 0.160, DRB1*1101, and 0.138, for DRB1*0301 and DRB1*0701. The DQA1 and DQB1 loci are less polymorphic. Among the 8 DQA1 alleles detected, DQA1*0501 is highly predominant with a frequency of 0.383. Thirteen DQB1 alleles are observed among which DQB1*0301 and DQB1*0201 are the most frequent (0.351 and 0.245, respectively). Three haplotypes predominate clearly: DRB1*1101-DQA1*0501-DQB1*0301 (0.138), DRB1*0701-DQA1*0201-DQB1*0201 (0.128) and DRB1*0301-DQA1*0501-DQB1*0201 (0.117). The two latter are among the most frequent haplotypes found in European and North American Caucasoid populations, but the DQA1*0501-DQB1*0201 association is not significant in Algerians. The genetic distances computed for each locus among a set of populations from different continents are significantly correlated to geography. They indicate that the Algerians are very close to South European populations, particularly to Sardinians, Italians, Romanians and French, with some intermediate characteristics between Europeans and sub-Saharan Africans. These results may serve as reference for future studies of HLA and disease in the Algerian population.     

HLA class II antigens in South African Blacks with type I diabetes

Type 1 diabetes mellitus is poorly characterised in many African communities, including South Africa, where little is known of the disease epidemiology. This study aimed to identify the HLA class II alleles associated with type 1 diabetes in a group of Zulu subjects in Durban, KwaZulu-Natal by PCR-SSP. The HLA alleles associated with type 1 diabetes included HLA-DQB*0302 (P<0.0001), DRB1*O9 (P<0.0001), DRB1*04 (P=0.002), DRB1*0301 (P=0.003), DQB*02 (P=0.004) and DQA*03 (P=0.035). Estimated haplotypes positively associated with type 1 diabetes included HLA-DRB1 *0301-DQA*0501, DRB1*04-DQA*03, DRB1*04-DQB*0302, DRB1*0301-DQB*0201, DQA*0501-DQB*0201 and DQA*03-DQB*0302. These findings are similar to those reported from Zimbabwe and other populations with type 1 diabetes.     

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 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.     

HLA class II DNA polymorphism in a Moroccan population from the Souss, Agadir area

Abstract: HLA DRB1, DQA1 and DQB1 polymorphisms were analyzed by PCR-SSO typing in a sample of the Moroccan population from Souss. Uneven allelic frequency distributions are observed at each locus, with particularly high frequencies for DRB1*0701, DRB1*0301, DQA1*0501, DQA1*0201, and DQB1*0201. Only three haplotypes (DRB1*0701-DQA1*0201-DQB1*0201, DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*11-DQA1*0501-DQB1*0301) account for nearly 50% of the total gene frequencies. A genetic distance analysis reveals that the Moroccan population is close to the Spanish and the Algerians, who live in geographically neighboring areas. However, the Souss population is also characterized by a lower level of genetic diversity compared to other African and European populations from the Mediterranean area. This may be the result of a rapid genetic drift due to their likely geographical and/or cultural isolation.     

Polymorphism in the upstream regulatory region of the DQB1 gene (QBP) and four point (DRB1, QBP, DQA1, DQB1) haplotypes in the Dai minority population in China.

Using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides we have investigated the DNA polymorphism for the DQB1 promoter region (QBP) and we have deduced four point haplotypes in 65 unrelated healthy individuals of the Dai minority population. A total of 8 QBP alleles were detected. The most frequent allele is QBP 5.11 with 87.7% allele frequency followed by QBP 3.21, 3.1, 5.12 with 33.8%, 23.1% and 15.4% allele frequency respectively. Four QBP alleles, 3.22, 3.32, 4.1 and 6.12 were absent in the Dai minority. The linkage disequilibrium of the QBP allele with certain DQB1 alleles was very strong. Complete positive association was found for QBP 2.1-DQB1^*0201, QBP3.1-DQB1^*0301, QBP6.11-DQB1^*0601. A total of 32 different four point haplotypes were deduced. Among them the most common haplotypes were DRB1^*1602, DQA1^*0102, QBP5.11; DQB1^*0502, DRB1^*1602-QBP5.11, DQA1^*0102, DQB1^*0502 (N = 19); DRB1^*09 DQA1^*03, QBP3.21, DQB1^*03032 (N = 5); DRB1^*1401, DQA1^*01, QBP5.11, DQB1^*0502 (N = 12) and DRB1^*1202, DQA1^*0601, QBP3.1, DQB1^*0301 (N = 10). We conclude from these data that a) there is a reduced class II polymorphism in the Dai minority population an b) the relationship between QBP and DQB1 alleles is not different from that observed in other populations.     

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.     

Haplotypic diversity of DQA1*03 and *05 subtypes differing at amino acid residue 160 encoded in the third exon in 2215 Japanese individuals

We analyzed the frequencies and haplotypes of DQA1*03 and *05 subtypes, DQA1*03011 or DQA1*0302 and DQA1 *0501 or DQA1*0503, respectively, differing only at codon 160 in the non-polymorphic third exon of the DQA1 gene. Of these, 1,862 and 337 individuals selected as DQA1*03- and DQA1**05-positive samples, respectively among 2,215 unrelated Japanese were typed for their nucleotide variation at residue 160 using PCR-SSP. As observed in other populations, all the samples carrying DQA1*03011 (Gene Frequency, GF: 7.8%) were found to share DQB1*0302, whereas those carrying DQA1*0302 (GF: 44.3%) were associated with a variety of DQB1 alleles including DQB1*0302. Both of the DQA1-DQB1 haplotypes with DQA1*03011 and DQA1*0302 carrying DRB1*0406, DQA1*03011-DQB1*0302 and DQA1*0302-DQB1*0302, showed a strong linkage disequilibrium with B62 (p< .0001, p< .005). These results suggested that DQA1*03011 was generated from a single amino acid change at residue 160 in the DQA1*0302-DQB1*0302 haplotype. However, none of the haplotypes with two different DQA1*03 subtypes carrying DRB1*0403, *0405, *0802 and *0901 showed a linkage disequilibrium with any common B-locus antigens, revealing extensive haplotypic diversity of the DQA1*03 group. For example, DRB1*0802 haplotypes showed linkage disequilibria with two different B-locus antigens, B35 and B61 depending on the presence of DQA1*03011 and DQA1*0302, respectively. The GFs of DQA1*0501 and *0503 were 5.1% and 2.7%, respectively. The DQA1*05 associated haplotypes in the DR52-antigen group with DQB1*0301 were divided into two groups, depending on the bimorphism at residue 160. Such a high degree of haplotypic diversity in association with DRB1 and B alleles observed in the DQA1*03 and *05 groups related to amino acid variation at residue 160, which may affect biological function such as the interaction between CD4 and HLA-DQ molecules, seems to reflect selective pressure in the evolutionary process of HLA antigens     

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.     

Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in the Dai minority population in South-Western China

We have investigated the polymorphism of the DQA1 promoter region (QAP) and we have deduced four point (DRB1, QAP, DQA1, DQB1) haplotypes of 60 unrelated healthy Dai minority individuals using the polymerase chain reaction and Dig-ddUTP labeled oligonucleotides. A total of eight QAP alleles (QAP1.1, 1.2, 1.3, 1.4, 3.1, 3.2, 4.1 and 4.2) were detected and two QAP alleles, QAP1.5 and QAP2.1 were absent in this population. The most predominant allele was QAP1.2 with 80% allele frequency. We also found that QAP alleles are in strong linkage disequilibrium with certain alleles of the neighboring loci DQA1 and DQB1. Complete positive association was found for QAP4.1-DQA1^*05, QAP4.2-DQA1^*0601, QAP1.2-DR2 group, QAP3.2-DRB1^*09, QAP4.1-DRB1^*03. A total of 28 different four point (DRB1-QAP-DQA1-DQB1) haplotypes were deduced and the most frequent haplotypes were DRB1^*1602-QAP1.2-DQA1^*0102-DQB1^*0502 (N = 18, H.f. = 15%) and DRB1^*09-QAP3.2-DQA1^*03-DQB1^*03032 (N = 18, H.f. = 15%) followed by the haplotypes DRB1^*1401-QAP1.3-DQA1^*01-DQB1^*0502, DRB1^*1202-QAP4.2-DQA1^*0601-DQB1^*0301 and DRB1^*1502-QAP1.2-DQA1^*0101-DQB1^*0501 with H.f. 9.1%, 6.7% and 5.0% respectively. The other 23 haplotypes were all less than 5% (H.f. 0.8%-5%). The relationship between the QAP alleles and DQA1 in the Dai minority is the same as that in the Chinese and the Caucasoid population.     

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.     

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.     

Molecular analysis of HLA allelic frequencies and haplotypes in Jordanians and comparison with other related populations.

Twenty alleles for the locus human leukocyte antigen (HLA-A) and 46 for the HLA-B locus were detected in Jordanians. This indicates the existence of high polymorphism in this area. The most frequent HLA class I alleles found were A*0201 (0.1344), B*0713 (0.1724), and C*0502 (0.1793). Twenty-six different alleles in the Jordanian population were identified for the DRB1 locus being the DRB1*0704 (0.2552), DRB1*0401 (0.1965), and DRB1*1501 (0.0896) the most frequent. Common DQA1 alleles were DQA1*0201 (0.2690), DQA1*0301 (0.2414), and DQA1*0501 (0.1724). Three-loci haplotype heterogeneity was common: 38 HLA class II haplotypes were identified, of which the most frequently observed was DRB1*0401-DQA1*0301-DQB1*0302 (0.1793). In addition, as expected, 220 different five-loci haplotypes with several unusual allelic combinations were observed, although many of them are pan-European haplotypes. The most frequent five-loci haplotype was the A30-B7-DRB1*03-DQA1*0501-DQB1*0201 (0.0138). It seems that the specific Jordanian haplotypes are the following: the A31-B7-DRB1*04/07-DQA1*0301/0201-DQB1*0302/0202 haplotypes (0.0103) and the A1-B7-DRB1*07-DQA1*0201-DQB1*0202, A2-B7-DRB1*04-DQA1*0301-DQB1*0302, A11-B7-DRB1*07-DQA1*0201-DQB1*0201 haplotypes but at lower frequencies (0.007). A tree analysis of HLA class I and class II alleles were made for several Caucasian populations and individual genetic distances calculated. The haplotype frequencies, genetic distances, and dendrograms do not reveal great differences as compared with those in other Mediterranean countries and Western Europeans populations. Our results suggest that both HLA class I and class II polymorphism (but especially the former) of the Jordanian population demonstrates considerable heterogeneity, which reflects ancient and recent admixture with neighboring populations, and important human migratory trends throughout the history.     

HLA-DRB and -DQB1 polymorphism in the Macedonian population

HLA-DRB1, DRB3/4/5 and DQB1 polymorphism has been studied in a population of 80 unrelated healthy Macedonians using molecular methods. Twenty-five different DRB1 alleles were identified of which DRB1*1104, *1501, *1601, and *1101 were found most frequently. Among the 15 identified DQB1 alleles, two were predominant: DQB1*0301 and *0502. The most frequent three-locus haplotypes were DRB1*1104-DRB3*02-DQB1*0301 (18%/), DRB1*1101-DRB3*02-DQB1*0301 (9%) and DRB1*1601-DRB5*02-DQB1*0502 (10%). Polymorphism for DRB1*04, *13 and *15 haplotypes was extensive. Eleven different DR2-related haplotypes were found, some of which were unusual for European populations: DRB1*1501-DRB5*0102-DQB1*0502, DRB1*1501-DRB5*02-DQB1*0502, DRB1*1501-DRB5*0102-DQB1*0601.     

Class II allele and haplotype frequencies in Mexican systemic lupus erythematosus patients: the relevance of considering homologous chromosomes in determining susceptibility

The aim of the present study was to determine the relevant major histocompatibility complex (MHC) class II alleles in the genetic susceptibility to systemic lupus erythematosus (SLE) in Mexican Mestizo patients. We examined the gene and haplotype frequencies of the HLA-DRB1, DQA1 and DQB1 alleles by polymerase chain reaction-sequence-specific oligonucleotide probes in 81 Mexican SLE Mestizo patients and 99 ethnically matched controls. We found a significantly increased frequency of the HLA-DRB1*0301 (p(c) = 0.031, odds ratio = 2.63) allele and significantly decreased frequencies of the DRB1*0802 (p(c) = 0.035) and DRB1*1101 (p(c) = 0.037) alleles in the SLE group. Haplotype analysis showed increased frequencies of DRB1*0301-DQA1*0501-DQB1*0201 (p(c) = 0.017, odds ratio = 2.97), and decreased frequency of DRB1*0802-DQA1*0401-DQB1*0402 (p(c) = 0.034) in SLE patients. The most frequently detected haplotypes in SLE patients showed different haplotypic combinations in the homologous chromosome from those found in controls. Thus, the combinations detected in SLE patients were either not detected in the control group or infrequently found. The results suggest that the DRB1*0301 is the principal class II allele associated with the genetic susceptibility to SLE in Mexican patients and that the presence of a specific haplotype of the homologous chromosome in patients with DRB1*0407-DQA1*03-DQB1*0302 and DRB1*1501-DQA1*0102-DQB1*0602 haplotypes could have an additive effect on the susceptibility to the disease. Finally, the low frequency of the DRB1*0301 and DRB1*1501 alleles in the control population suggests that the genetic admixture between Mexican Indians and Caucasian populations was an event that could have increased the risk of Mexicans to develop SLE.