Association of HLA-A*3303-B*4403-DRB1*1302 haplotype,but not of TNFA promoter and NKp30 polymorphism,with postherpetic neuralgia (PHN) in the Japanese population

Herpes zoster is a common disease caused by reactivation of the varicella zoster virus (VZV). In a small number of herpes zoster patients, pain persists beyond 4 weeks or more after healing of vesicular eruptions; this condition is termed postherpetic neuralgia (PHN). Positive associations of human histocompatibility leukocyte antigens (HLA) class I antigens, A33 and B44, with PHN in the Japanese population have been reported. Our hypothesis is that susceptibility genes to PHN might exist in the HLA region and the study objective is to further examine possible associations of genes in HLA class I, II and III regions, HLA-A, -B, -DRB1, tumor necrosis factor alpha (TNFA) promoter, and a natural killer cell activating receptor, NKp30 polymorphisms with PHN. Although TNFA or NKp30 in the class III region had been considered as a candidate locus, we found no associations of TNFA promoter or NKp30 polymorphisms with PHN in this study. We demonstrated that HLA-A*3303, -B*4403 and -DRB1*1302 alleles were significantly associated with PHN (P = 0.0007 for A*3303, P = 0.001 for B*4403 and P = 0.001 for DRB1*1302). The frequency of the HLA-A*3303-B*4403-DRB1*1302 haplotype was also significantly higher in the PHN patients than in the healthy controls (P = 0.0039). Our results suggest that this haplotype might be related to the pathogenesis of PHN.     

Striking conservation of three extended HLA-DR13 haplotypes in the Japanese population

Abstract: HLA class II DNA typing was conducted for 1335 unrelated Japanese individuals. The study on the linkage disequilibrium revealed a striking conservation of HLA DR13 haplotypes. Among these Japanese, 155 were typed for HLA-DR13 serologically, and they were correspondent to three DRB1 alleles, DRB1*1301, 1302 and 1307 defined by using the polymerase-chain reaction and sequence-specific oligonucleotide probe (PCR-SSOP) method. The two alleles, DRB1*1301 and 1307 were exclusively associated with each specific DRB3-DQA1-DQB1 combination which was DRB1*1301-DRB3*0101-DQA1*0103-DQB1*0603, and DRB1*1307-DRB3*0202-DQA1*0501-DQB1*0301, respectively. DRB1* 1302, the most common DR13 allele in Japanese, had two significant associations with DRB3*0301-DQA1*0102-DQB1*0604 (DRB1*1302A) and with DRB3*0301-DQA1*0102-DQB1*0605 (DRB1*1302B). In this study, no other DR13 class II combinations were found. Ony the DRB1*1302A halotype was associated with the DPB1*0401 allele while the DRB1*1302B haplotype was not. The complete conservation of these DR13 class II haplotypes was found to extend toward the HLA class I region. They were HLA A3-B44-DRB1*1301, A33-B44-DRB1*1302A and A33-B17-DRB1*1302B. Japanese could be characterized with these three extended haplotypes which were remakrably different from those in Caucasian, Black and Asian other than Korean populations.     

Serological and molecular analysis of HLA class I and II alleles in Thai patients with psoriasis vulgaris

Abstract: The HLA class I and class II alleles in 67 patients with type I psoriasis vulgaris, 23 patients with type II psoriasis vulgaris and 140 healthy individuals were analyzed. The frequencies of HLA-A2, -B46, -B57 and DQB1*0303 were significantly increased in type I psoriasis compared to the controls (Pc<0.05). Molecular analysis of HLA-A2 alleles showed an increase in HLA-A*0207 and a decrease in HLA-A*0203 in type I psoriasis. HLA-DQBl*0301 was significantly decreased in type I psoriasis compared to the normal controls (Pc<0.05). No association of any alleles with type II psoriasis was observed. This data demonstrated two susceptible haplo-types: HLA-A1-B57-DRB1*0701-DQA1*0201-DQB1*0303 (AH57.1) and HLA-A2-B46-DRB1*0901-DQA1*0301-DQB1*0303 (AH46.1) for type I psoriasis in the Thai population. Besides, the haplotype AH46.1 was also associated with type II psoriasis.     

HLA-A, -B and -DRB1 allele frequencies in the Bangladeshi population

Population genetic studies have become an invaluable tool because of the extreme polymorphism found at some of the loci of the human leukocyte antigen (HLA) system. In this study, we are reporting for the first time the genetic polymorphism of 141 healthy unrelated Bangladeshi Bangalees living in central region of Dhaka. We studied the HLA-A, -B and -DRB1 loci using polymerase chain reaction with sequence-specific primers. The allelic frequencies, two and three locus haplotype frequencies were statistically analyzed. A total of 16 HLA-A alleles, 26 HLA-B alleles and 14 HLA-DRB1 alleles were detected. A*33-B*44 (8.15%) was the most common two loci class 1 haplotype, whereas A*33-B*44-DRB1*07 (6.38%) was the most frequent three loci haplotype. The most common HLA-A, HLA-B and HLA-DRB1 alleles were A*33 (17.02%), B*15 (19.5%) and DRB1*15 (29.07%), respectively. Construction of phylogenetic tree using average linkage between groups and correspondence analysis showed close associations with Indian non-tribal random Dravidians, north Indian Hindus and some relations with Mongolian and Pakistani populations. We believe this data will provide useful information for bone marrow registry, legal medicine, disease association and anthropological studies.     

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.     

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   

Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran compared with related populations of Pakistan

The extreme polymorphism in different loci of the human leukocyte antigen (HLA) system has been used as an invaluable tool for anthropological studies. Determination of HLA allele and haplotype frequencies in different ethnic groups is useful for population genetic analyses and the study of genetic relationships among them. In the present study, molecular analysis of HLA-A, -B, -C, -DQA1, -DQB1, and -DRB1 genes has been used to assign HLA allele and haplotype frequencies in 100 unrelated healthy individuals from the Baloch ethnic group of Iran. The results were compared with Baloch and other ethnic groups in the neighboring Pakistan. The results of this study showed that the most frequent HLA class I alleles were A*02011 (20.2%), B*4006 (11.1%), and C*04011 (28.6%). The most common HLA class II alleles were DQA1*0101/2 (42.5%), DQB1*0201 (32%), and DRB1*0301 (29%). Three-locus haplotype analysis revealed that A*11011-B*4006-C*15021 (5.8%) and DQA1*0501-DQB1*0201-DRB1*0301 (22.1%) were the most common HLA class I and II haplotypes, respectively, in this population. Neighbor-joining tree based on DA genetic distances and correspondence analysis according to HLA-A, -B, -DQB1, and -DRB1 allele frequencies showed that Baloch of Iran are genetically very close to Baloch and Brahui of Pakistan. This may reflect an admixture of Brahui and Baloch ethnic groups of Pakistan in the Balochistan province of Iran.     

Molecular analysis of HLA class I (HLA-A and -B) and HLA class II (HLA-DRB1) genes in Japanese patients with multiple sclerosis (Western type and Asian type)

Abstract: The types of HLA-A, -B and -DRB1 genes were studied in 146 Japanese patients with multiple sclerosis (MS) using polymerase chain reaction-sequence-specific oligonucleotide probe analysis. Fifty-seven patients who displayed selective clinical involvement of the optic nerve and spinal cord were classified as having Asian type MS. The other 89 patients had disseminated central nervous system involvement and were classified as having Western type MS. The frequency of HLA-B*5101 was increased in both types of MS patients compared with controls. The frequency of HLA-DRB1*1501 was increased in Western type MS and the frequency of HLA-DRBl*0802 was increased in Asian type MS compared to controls. After correction of P values, the association of Western type MS patients with HLA-DRB1*1501 was statistically significant ( Pc =0.0003) whereas other HLA alleles showed no significant association. These results suggest that HLA class I (HLA-A and -B) alleles may not contribute to a strong susceptibility to MS in Japanese compared to HLA class II (HLA-DRB1) alleles.     

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.     

Distribution of MICA alleles and haplotypes associated with HLA in the Korean population

The MICA (MHC class I chain-related gene A) is a polymorphic gene located 46 kb centromeric of the HLA-B gene, and is preferentially expressed in epithelial cells and intestinal mucosa. The MICA gene, similar to human leukocyte antigen (HLA) class I, displays a high degree of genetic polymorphism in exons 2, 3, 4, and 5, amounting to 54 alleles. In this study, we investigated the polymorphisms at exons coding for extracellular domains (exons 2, 3, and 4), and the GCT repeat polymorphism at the transmembrane (exon 5) of MICA in 199 unrelated healthy Koreans. Eight alleles were observed in the Korean population, with allele frequencies for MICA*010, MICA*00201, MICA*027, MICA*004, MICA*012, MICA*00801, MICA*00901, and MICA*00701 being 18.3%, 17.8%, 13.6%, 12.3%, 11.1%, 10.8%, 10.6%, and 3.3%, respectively. Strong linkage disequilibria were also observed between the MICA and HLA-B gene-MICA*00201-B58, MICA*004-B44, MICA*00701-B27, MICA*00801-B60, MICA*00901-B51, MICA*010-B62, MICA*012-B54, and MICA*027-B61. In the analysis of the haplotypes of HLA class I genes (HLA-A, B, and C) and the MICA, the most common haplotype was MICA*004-A33-B44-Cw*07, followed by MICA*00201-A2-B58-Cw*0302 and MICA*012-A2-B54-Cw*0102. The MICA null haplotype might be identified in the HLA-B48 homozygous individual. These results will provide an understanding of the role of MICA in transplantation, disease association, and population analyses in Koreans.     

Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease

Multiple sclerosis (MS) is a presumed autoimmune disease of the central nervous system, shown to be associated with the HLA class II haplotype DRB1*15,DQB1*06. Carrying the HLA class II haplotype DRB1*15,DQB1*06 increases the risk of MS by 3.6. By adopting a polymerase chain reaction (PCR)-based typing technique for HLA class I and class II genes, 200 Swedish MS patients and 210 Swedish healthy controls were analysed for their HLA alleles. Additional HLA class I alleles that increase and decrease the genetic susceptibility to MS were identified. The HLA-A*0301 allele increases the risk of MS (odds ratio=2.1) independently of DRB1*15,DQB1*06. HLA-A*0201 decreases the overall risk (odds ratio= 0.52) and the presence of A*0201 reduces the risk of MS for DRB1*15,DQB1*06 carriers from 3.6 to 1.5. Our findings are the first to identify a major modulating effect of HLA class I alleles on the susceptibility to a human autoimmune disease; a phenomenon that has previously only been observed in animal models.     

HLA antigens in Greek children with allergic bronchial asthma

Abstract:  The aim of our study was to investigate the genetic linkage between mite allergic bronchial asthma and HLA class I and II antigens and haplotypes. Sixty Greek children with allergic bronchial asthma due to mite sensitivity ( Dermatophagoides pteronyssinus and Dermatophagoides farinae ) and their family members were typed for HLA class I and II antigens (total 263 subjects). One hundred and twenty-five healthy, unrelated Greek children without medical history of atopy were also typed as control group. Major histocompatibility complex class I and II gene analysis revealed that only HLA-DRB1*04 and HLA-DQA1*0301 alleles are possibly important factors in the development of atopic asthma in Greek children with sensitivity to mites. No significant differences among the HLA-DRB1*04 subtypes have been established. Transmission disequilibrium test revealed that no specific HLA-A, -B, -DRB1, -DQA1 and -DQB1 alleles were transmitted preferentially to the affected children. HLA-DQB1*0301-4 alleles were associated with high levels of total serum immunoglobulin E in affected children. The study of the HLA haplotypes failed to demonstrate any significant association between any extended or natural selection haplotype and mite allergic bronchial asthma in Greek children.     

Diversity of HLA-B17 alleles and haplotypes in East Asians and a novel Cw6 allele (Cw*0604) associated with B*5701

The distribution of HLA-B17 alleles and their association with HLA-A, -C and -DRB1 alleles were investigated in seven East Asian populations Japanese, South Korean, Chinese-Korean, Man, Northern Han, Mongolian and Buryat populations). The B17 alleles were identified from genomic DNA using group-specific polymerase chain reaction (PCR) followed by hybridization with sequence-specific oligonucleotide probes (SSOP). In all of these East Asian populations, except Japanese and Chinese-Koreans, B*5701 was detected and strongly associated with A*0101, Cw*0602 and DRB1*0701. In contrast, B*5801 was detected in all the seven populations and strongly associated with A*3303, Cw*0302, DRB1*0301 and DRB1*1302. The A*3303-Cw*0302-B*5801-DRB1*1302 haplotype was observed in South Korean, Chinese-Korean, Buryat and Japanese populations, while A*3303-Cw*0302-B*5801-DRB1*0301 was predominantly observed in the Mongolian population. A similar haplotype, A*0101-Cw*0302-B*5801-DRB1*1302, was observed in the Buryat population. A novel Cw6 allele, Cw*0604, was identified in the Man population. This Cw allele was observed on the haplotype A*0101-B*5701-DRB1*0701. Thus, we confirmed, at the sequence level, that the common haplotypes carrying B*5701 and B*5801 have been conserved and shared in East Asian populations.     

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.     

Allele and extended haplotype polymorphism of HLA-A, -C, -B, -DRB1 and -DQB1 loci in Polish population and genetic affinities to other populations

Human leukocyte antigen (HLA)-A, -C, -B, -DRB1 and -DQB1 alleles were typed in 200 Polish healthy volunteers recruited for stem cell donor registry, using sequence-specific primer (SSP) and direct sequencing-based methods. Enhanced Bayesian approach of expectation maximization algorithm provided by phase platform was used for extended HLA haplotype inferences. The numbers of identified alleles (four-digit resolution) were 23, 23, 44, 27 and 18 alleles in HLA-A, -C, -B, -DRB1 and -DQB1 loci, respectively, of both northern and southern European frequency characteristics. The most frequent extended haplotypes were Cw*0701-B*0801-DRB1*0301-DQB1*0201 and Cw*0702-B*0702-DRB1*1501-DQB1*0602, found in 25 and 23 copies, respectively, in 400 tested chromosomes. The extended haplotype found in the Polish population with higher frequency than in other European population was A*2501-Cw*1203-B*1801-DRB1*1501-DQB1*0602 (six copies) and especially its class I fragment (14 copies). The neighbour-joining and correspondence analyses showed Central and northern European genetic affinities of Polish population. In most cases, the observed European allele and haplotype gradients display smooth topography around Polish population. Poles along with Western Slavs have their specific contribution in the demographic history of Europe. Our results will intensify the use of population data in stem cell donor search and can potentially improve current algorithms, facilitating selection of acceptable donors for patients in need of stem cell transplant.     

Genetic variation and hitchhiking between structurally polymorphic Alu insertions and HLA-A, -B, and -C alleles and other retroelements within the MHC class I region

We investigated structurally polymorphic Alu insertions (POALINs) at five loci in the major histocompatibility complex (MHC) class I genomic region to determine their allele and haplotype frequencies and associations with the human leukocyte antigen (HLA)-A, -B, and -C genes in three populations, the Australian Caucasians, Japanese, and African Americans. The POALINs varied in allelic frequency between 0% and 42.3% with significant differences between populations at three of the five loci. The linkage disequilibrium (LD) between Alu insertions and the HLA-A, -B, or -C alleles and previously published polymorphic retroelements (four SVA and human endogenous retrovirus type 9 (HERVK9) loci) within the class I region of the MHC were calculated in pairwise analyses of haplotypes to show strong allelic associations and possible crossing-over events between some loci. Each POALIN was in significant LD with a variety of HLA-A, -B, or -C two-digit alleles probably as a result of hitchhiking. The POALINs helped to further stratify the HLA-A:B:C haplotypes into different POALIN:HLA-A:B:C haplotype frequencies. Of the multilocus haplotype analyses, the seven- and eight-locus haplotypes showed the largest number of differences between the populations, and fewer matched haplotypes between populations that ranged, for example, from 49% for HLA-B:HLA-A haplotypes to 7% for AluMICB:HLA-B:HLA-C:AluTF:AluHJ:HLA-A:AluHG:AluTF haplotypes in the Japanese. This comparative study of multilocus POALINs in the HLA class I region of three ethnic populations shows that POALINs alone or together with the HLA class I alleles and other retroelements are informative ancestral markers for assessing the interrelationship of HLA class I haplotype lineages, LD, and genetic diversity within the same and/or different populations.     

The contribution of HLA class I and II alleles and haplotypes to the investigation of the evolutionary history of Tunisians

The frequencies of HLA class I and class II alleles and haplotypes of 104 healthy unrelated Tunisians were analyzed by high-resolution PCR-reverse dot blot hybridization, and was compared with other Mediterranean and Sub-Saharan Africans using genetic distances measurements, Neighbor-joining dendrograms, correspondence, and extended haplotypes analysis. The most frequent HLA class I A alleles were A*02, A*24, and A*30, while the most frequent B alleles were B*44, followed by B*50, B*51, and B*07. Among HLA class II DRB alleles analyzed, the most frequent were DRB1*0301, DRB1*0701, DRB1*1501, followed by DRB1*1303 and DRB1*0102; for DQB1, they were DQB1*0301 and DQB1*0201. Three-locus haplotype analysis revealed that A*03-B*07-DRB1*1503 and A*02-B*44-DRB1*0402 were the most common HLA class I and II haplotypes in this population. Compared with other communities, our result indicate that Tunisians are very related to North Africans and Western Europeans, particularly Iberians, and that Tunisians, Algerians, and Moroccans are close to Berbers suggesting little genetic contribution of Arabs who populated the area in 7th to 8th century AD. The similarities and differences between Tunisians and neighboring and related communities in HLA genotype distribution provide basic information for further studies of the MHC heterogeneity among Mediterranean and North African countries, and as reference for further anthropological studies.     

The association between HLA-A, -B alleles and major histocompatibility complex class I polymorphic Alu insertions in four populations in China

The study of the association between polymorphic Alu insertions [human leukocyte antigen (HLA)-Alu] at five loci and HLA class I alleles at two loci allows for better identification of the origins and evolution of HLA class I region haplotypes in different populations. In the present study, we determined the frequencies of five HLA-Alus and their associations with HLA-A and -B alleles in Han, Wa, Maonan, and Jinuo populations. Our results showed a strong association between AluHG insertion and HLA-A*02 in all populations studied; however, the associations between AluHJ insertion and HLA-A*1101 and HLA-A*2402 and AluHF insertion and HLA-A*2601 were only observed in Han. The AluMICB insertion showed a strong association with HLA-B*5502 in Han, Maonan, and Jinuo. HLA-A*0101, HLA-A*0201, HLA-A*0203, HLA-A*1101, HLA-A*2402, HLA-A*2601, and HLA-A*3101 alleles were associated with one or more of the three different Alu elements within the alpha block as independent haplotypes, and HLA-A*0101, HLA-A*0201, HLA-A*0203, HLA-A*1101, and HLA-A*2402 alleles were associated with at least two different Alu insertions as a haplotype within the alpha block. We conclude that the HLA class I region haplotypes of the four populations were derived from different progenitor haplotypes, and relatively high rates of recombination between individuals with HLA-A alleles and different HLA-Alus occurred in this region.     

HLA class I and class II DNA typing and the origin of Basques

Abstract: Seven HLA class I and class II loci (HLA-A, B, C, DRB1, DQA1, DPA1 and DPB1) were typed at the DNA level in two populations of the Iberian Peninsula (100 Basque and 88 Catalan individuals) in order to unravel their genetic relationship and to compare these results with other European and Mediterranean populations. For the first time,- the frequencies of alleles and haplotypes for the class I HLA loci at the DNA level in these populations are presented. The most frequent haplotype in both populations is A*29-Cw*1601-B*44-DRB1*0701-DQA1*0201-DPA1*0103-DPB1*0401. Neither population differed markedly from the highly homogeneous European and Mediterranean genetic landscape. The Basques, a European outlier population according to classical genetic markers, appear to lie within the genetic European variation with a slight uniqueness and show no clear relationship to North African populations, as has been postulated in some previous HLA studies. Here, the range of possibilities provided by the highly polymorphic HLA system is stressed by using genetic distances, phylogenetic trees and principal component analyses in order to reconstruct population history.     

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.