HLA polymorphism in six ethnic groups from Pakistan

The extreme polymorphism found at some of the loci of the HLA system has made it an invaluable tool for population genetic analyses. In this study the genetic polymorphism of six Pakistani ethnic groups was investigated at the HLA-A, -B, -C, -DRB and DQB1 loci using polymerase chain reaction with sequence specific primers. The groups included in this study are the Baloch, Brahui and Sindhi from the south and the Burusho, Kalash and Pathan from the north of Pakistan. The allele frequencies, three-locus haplotype frequencies for HLA-A, -C, -B and HLA-A, -B, -DRB1 are given. Variation in the allele and haplotype distribution between the six Pakistani ethnic groups was observed. A phylogenetic tree and correspondence analysis based on HLA-A, -B, -C, -DRB1 and -DQB1 allele frequencies revealed the Kalash population to be distinct from the remaining Pakistani populations. The Baloch and Brahui were closely related to one another. The Sindhi were closer to the Pathan and Burusho populations than to the neighboring Baloch and Brahui populations, indicating admixture between the northern and southern populations of Pakistan. A phylogenetic tree and correspondence analysis comparing the Pakistani populations with various other world populations showed that the Pakistani ethnic groups lie within the cluster of Asian Indian populations. The three-locus haplotypes found in the Pakistani populations suggest an influence from Caucasian and Oriental 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.     

HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in the Kinh population in Vietnam

Allele and haplotype frequencies of the human leukocyte antigens (HLA) were studied in the Kinh Vietnamese population. We analyzed 170 unrelated healthy individuals. DNA-based HLA typing was performed using a microsphere-based array genotyping platform with sequence-specific oligonucleotide probes to distinguish HLA-A, -B, -C, -DRB1 and -DQB1 alleles. A total of 21 HLA-A, 37 HLA-B, 18 HLA-C, 25 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. HLA-A*1101, A*2402, A*3303, B*1502, B*4601, Cw*0102, Cw*0702, Cw*0801, DRB1*1202, DQB1*0301, DQB1*0303, and DQB1*0501 were found with frequencies higher than 10%. Two representative haplotypes bearing two to five HLA loci were A*1101-B*1502 and A*3303-B*5801 for HLA-A-B; Cw*0801-B*1502 and Cw*0102-B*4601 for HLA-C-B; B*1502-DRB1*1202 and B*4601-DRB1*0901 for HLA-B-DRB1; DRB1*1202-DQB1*0301 and DRB1*0901-DQB1*0303 for HLA-DRB1-DQB1; A*1101-Cw*0801-B*1502 and A*3303-Cw*0302-B*5801 for HLA-A-C-B; A*1101-B*1502-DRB1*1202 and A*2901-B*0705-DRB1*1001 for HLA-A-B-DRB1, A*1101-Cw*0801-B*1502-DRB1*1202-DQB1*0301 and A*2901-Cw*1505-B*0705-DRB1*1001-DQB1*0501 for HLA-A-C-B-DRB1-DQB1. Allele distribution and haplotype analysis demonstrated that the Vietnamese population shares HLA patterns with southern Chinese, Thai, Javanese and Micronesians, while it also retains unique characteristics.     

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   

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.     

Molecular analysis of HLA polymorphism in Khoton-Mongolians

We have investigated polymorphism of the HLA class I and class II genes in Mongolians for the first time using PCR-based techniques. A minor population of Khoton-Mongolians was studied and compared to the major Khalkh-Mongolian population. Eighty-five Khoton-and 41 Khalkh-Mongolian samples were analyzed for polymorphism in HLA-A, -B, -DRB1, -DRB3, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci using PCR-SSOP and PCR-RFLP methods. Allele and haplotype frequencies were calculated. The results were then compared to those obtained from other human populations. In Khoton-Mongolians, the frequency of HLA-B38, DRB1*0301, DQA1*0502, DQB1*0201 and DPB1*0401 were significantly higher than those in other Mongoloid populations including Khalkh-Mon-golians, Buryat, Chinese, Northern Han, Southern Han, Koreans and Japanese. In contrast, the frequency of HLA-A2, DQA1*0102, DPB1*0201 and DPB1*0501 were significantly lower in Khoton-Mongolians. Haplotype frequency analysis revealed that Khoton-Mongolians shared the same haplotypes specific to Mongoloids as well as to Caucasoids. On the other hand, several haplotypes were found to be specific for the Khoton. The phylogenetic tree analysis constructed by the NJ method based on allele frequencies of HLA-A, -B, -DRB1, -DQA1, and -DQB1 genes revealed that the Khoton belong to the Northeast Asian cluster and are most closely related to the Khalkh, Inner Mongolian, Uygur and Buryat populations. These data suggest a unique genetic background for Khoton-Mongolians. Furthermore, they are closely related genetically to both Mongoloids and Caucasoids.     

HLA-DP antigen and Takayasu arteritis

Sixty-four patients with Takayasu arteritis and 317 healthy individuals in the Japanese population were examined for HLA-A, -B and -C alleles by serological typing and for HLA-DR, DQ and DP alleles by DNA typing using PCR/SSOP analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601 and DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, DQB1*0401 alleles were significantly decreased. Strong linkage disequilibria among the increased alleles and among the decreased alleles were evident in the Japanese population. Therefore, the combination or haplotype of HLA-Bw52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 -DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another combination or haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer resistance to the disease. Because this is the first evidence for the association between an HLA-DP allele and Takayasu arteritis, we examined the nucleotide sequences of the DPB1*0901 allele from a patient and her healthy relatives and found no difference. The disease is therefore not caused by a mutated DPB1 gene.     

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.     

Estimation of human leukocyte antigen class I and class II high-resolution allele and haplotype frequencies in the Italian population and comparison with other European populations

The high-resolution (HR) allele and haplotype frequencies of class I and II human leukocyte antigen (HLA) system were determined in the Italian population from a sample of donors recruited in the Italian Bone Marrow Donor Registry (IBMDR). This study analyzed the HLA-A, -B, -C, -DRB1, and -DQB1 loci. Two different samples were used: donors HR typed at least for one allele, usually when selected for donor-recipient matching (respectively: 3596, 7591, 4715, 57345, and 8196), to make a list of the observed alleles and determine the relative frequencies of the alleles in each class of the corresponding antigen; donors HR randomly typed for both the alleles (respectively: 975, 1643, 1569, 22114, and 2087) to estimate the allele and haplotype frequencies, and two loci linkage disequilibrium. The number of alleles showing a frequency >1% on the total number of observed alleles are 18/75 HLA-A, 28/142 -B, 17/57 -C, 23/154 -DRB1, and 13/31 -DQB1. In each locus they account for more than 88% of the total cumulative frequencies. The most frequent alleles are A*02: 01, B*35: 01, C*04:01, DRB1*07:01, DQB1*03:01. The most frequent five-locus haplotype in the 338 donors randomly typed is A*01: 01-C*07:01-B*08: 01-DRB1*03:01-DQB1*02:01. The genetic comparison of the Italian population with 16 European populations shows a south-north gradient.     

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.     

Gorgan (Iran) population HLA genetics and anthropology

Gorgan (Iran) have been studied for HLA-A, -B, -C, -DRB1 and -DQB1 genes for the first time. They are Turkmen and originated in East Asia around Altai Mts; they originally spoke a Turk language classified within the Turkish-Oguz group. Peripheral blood samples were collected from Gorgan City (Iran) and HLA typed by standard methodology. HLA allele frequencies were compared with 7984 chromosomes of other World populations and it was shown existence of admixture of Siberian and Mediterranean HLA characters in this population, probably due to longlasting contact with Persians. Three new HLA extended haplotypes were found: A*01:01-B*35:01-DRB1*03:01-DQB1*02:01, A*30:01-B*13:01-DRB1*15:01-DQB1*02:01 and A*31:01-B*35:01-DRB1*15:01-DQB1*03:01. Gorgan (Iran) were most close to Chuvashians (Noth Caspian Sea, Russia) and Siberians, like Tuvinians, Mansi and Buryats in Neighbour Joining and Vista analyses. It is established a relationship of this population with Kurgan (Gorgan, Iran) archaeological mounds culture. However, their kinship with Scythians (2nd century BC) and Sarmatians (4th century AD) is obscure although both of them spoke a Persian language.     

HLA class II gene polymorphism in Parsees and Zoroastrians of Iran

Extensive polymorphism of the HLA genes in different ethnic groups has been used as an invaluable tool for anthropological studies. In this study, HLA-DRB1, DQA1 and DQB1 allele frequencies and haplotypes were determined in 72 Parsees and 65 Zoroastrians living in Iran. The predominant DRB1 allele was *1103 = 4 in Parsees and *0701 in Zoroastrians. DQA1*0501 was the most common alleles in both spopulations. The most frequent DQB1 allele was *0301 in Parsees and *0201 in Zoroastrians. DRB1*1103 = 4-DQA1*0501-DQB1*0301 and DRB1*0701-DQA1*0201-DQB1*0201 were the most prevalent haplotypes in Parsees and Zoroastrians, respectively. Significant deviation from Hardy-Weinberg equilibrium was observed in DQA1 and DQB1 loci of Zoroastrians. The former locus also departed from neutrality due to balancing selection. All pairs of the studied loci in this study showed significant linkage disequilibrium. Analysis of molecular variance indicated that the main variation was confined to individuals within the studied populations. Neighbour-joining tree based on Nei's genetic distances according to DRB1 and DQB1 allele frequencies showed that Parsees and Zoroastrians of Iran were located in the same cluster of the phylogenetic tree. Furthermore, Zoroastrians of Iran and Pakistan are very close to each other. This study will serve as a reference for further anthropological studies when the HLA profile of all ethnic groups of Iran is investigated.     

HLA class I and II polymorphisms in the Gujjar population from Pakistan

HLA polymorphisms at the HLA -A, -B, -C, -DRB and -DQB1 loci were investigated in the Gujjar population from the Punjab province of Pakistan. The Gujjars (n?=?97) were genotyped using sequence specific primers for polymerase chain reaction. The allele and haplotype frequencies were calculated and a neighbor-joining (NJ) tree comparing the Gujjar with other populations was constructed. The class I allelic groups with a frequency greater than 10% include A*01, A*02, A*11, A*26 and A*31 at the HLA-A locus, B*08 and B*51 at the HLA-B locus and C*07 and C*14 at the HLA-C locus. Among the 12 allelic groups detected at the DRB1* locus, *03, *13, and *15 were present at frequencies higher than 10% whereas at the DQB1 locus, the allelic groups*06 and *02 accounted for over half of the Gujjar population. HLA-A*31-B*51-DRB1*13 was the most common (8.8%) haplotype in this population. A NJ tree revealed that the Pakistani Gujjar are closely related to the Golla tribe from Andhra Pradesh in India. The two populations are dedicated to the same profession, cattle breeding. HLA analyses of additional Punjab castes would provide valuable information for anthropological, organ transplantation and genetic disease studies.     

5-Locus high-resolution HLA allele and haplotype frequencies in Costa Ricans from the Central Valley

A total of 221 Costa Rican Mestizos from the Central Valley were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, -DRB1, and -DQB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified was A*24:02:01-B*40:02:01-C*03:05-DRB1*08:02:01-DQB1*04:02:01, with an estimated frequency of 2.04%. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name “Costa Rica Central Valley Mestizo” and the identifier AFN3606.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

HLA profile of the Macedonian,Albanian and Macedonian Muslim donors in the Macedonian Bone Marrow Donor Registry

The aim of this study was to determine the HLA allele and haplotype frequencies of the volunteer donors from the Macedonian Bone Marrow Donor Registry (MBMDR). We analyzed 1541 donors, from different nationalities and presented the HLA allele and haplotype frequencies for Macedonian, Albanian and Macedonian Muslims, most numerous nationalities in MBMDR. Difference between the three groups was observed for allele frequencies in HLA-C and HLA-DRB1 loci. The most common haplotype in Macedonian was HLA-A*01-B*08-C*07-DRB1*03, while in Albanian and Macedonian Muslims HLA-A*02-B*18-C*07-DRB1*11. This study confirmed the close relationship between the populations that live in the Balkan Peninsula.     

HLA class II similarities in Iranian Kurds and Azeris

The genetic relationship between Kurds and Azeris of Iran was investigated based on human leukocyte antigen (HLA) class II profiles. HLA typing was performed using polymerase chain reaction/restriction fragment-length polymorphism (PCR/RFLP) and PCR/sequence-specific primer (PCR/SSP) methods in 100 Kurds and 100 Azeris. DRB1*1103/04, DQA1*0501 and DQB1*0301 were the most common alleles and DRB1*1103/04-DQA1*0501-DQB1*0301 was the most frequent haplotype in both populations. No significant difference was observed in HLA class II allele distribution between these populations except for DQB1*0503 which showed a higher frequency in Kurds. Neighbor-joining tree based on Nei's genetic distances and correspondence analysis according to DRB1, DQA1 and DQB1 allele frequencies showed a strong genetic tie between Kurds and Azeris of Iran. The results of amova revealed no significant difference between these populations and other major ethnic groups of Iran. No close genetic relationship was observed between Azeris of Iran and the people of Turkey or Central Asians. According to the current results, present-day Kurds and Azeris of Iran seem to belong to a common genetic pool.     

HLA alleles and haplotypes in Iran Tabriz Azeris population: genes and languages do not correlate

Azeri people are at present day mainly living in an area which comprises North (Azerbaijan) and South (Azeri Iran provinces) parts, living the biggest population in Azeri Iran provinces with about 17–20 million people. They were studied HLA-A, -B, -DRB1 and -DQB1 allele and extended haplotype frequencies in unrelated Iranian Tabriz Azeris from a rural area close to Tabriz City. The HLA extended haplotypes with highest frequencies are: 1) HLA- A*24:02-B*35:01-DRB1*11:01-DQB1*03:01, shared with Mediterraneans and southern Russians (Chuvash, which also show Mediterranean characters); and 2) HLA-A*01:02-B*08:01-DRB1*03:01-DQB1*02:01, found also in Chuvash and other Azeri samples from Tabriz. Neí’s DA HLA-DRB1 genetic distances, HLA-DRB1 Neighbour-Joining dendrogram and Vista analyses show that population with closest distance is Kurdish, followed by Iranian Gorgan and Southern Russia/ North Caucasus Chuvash; probably these latter groups and Azeris were populating North Mesopotamia/ Caucasus Mts. since prehistoric times. Kurds (in Iraq and Iran) do not speak Turk while Azeris do: they are both genetically close, but they are not genetically close to present day Anatolia (Turkey) Turks who also speak Turk language and show a typical Mediterranean HLA profile. In summary, Azeri population studies show examples that genes and languages do not correlate, contradicting the postulate asserted by others.     

Diversities of HLA-A, -B, -C, -DRB1 and -DQB1 loci in Chinese Kazak population and its genetic relatedness dissection with multiple populations: a comparative study

Studying the allele and haplotype distributions of human leukocyte antigen (HLA) loci at 2nd-field level in different populations was important. Allele and haplotype frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 loci in 110 unrelated healthy Kazak individuals living in Xinjiang (China) were analyzed using polymerase chain reaction sequence based typing. Thirty HLA-A, 48 HLA-B, 24 HLA-C, 34 HLA-DRB1 and 18 HLA-DQB1 alleles were detected at the 2nd-field level in the Kazak population. Frequencies of HLA alleles, genotypes, and haplotypes were calculated, and some exhibited significantly different distributions among different populations. A neighbor-joining (NJ) tree, heatmap, multidimensional scaling (MDS) and principal component analysis (PCA) were used to explore the genetic relationships between the Kazak population and 32 reference populations distributed in Asia, Africa, America and Europe using frequency data of HLA-A, -B, -C and -DRB1 loci. The NJ tree, heatmap, and MDS of the 33 populations were constructed based on pairwise D_A values of populations obtained by the HLA-A, -B, -C and -DRB1 allele frequencies. Different PCA plots were constructed based on the allele frequencies of HLA-A, -B, -C and -DRB1 or estimated haplotypic frequencies of HLA-A, -B, -C loci. The data obtained in the present research can be used for research on HLA-related diseases or paternity relationships, and aid to finding the best matched donors in stem cell transplantation for Kazak individuals.     

Comparison of TAP2 frequencies in type 1 diabetes patients and healthy controls from three ethnic groups indicates an African origin for the TAP2 G allele.

In order to determine the ethnic origin of the transporter associated with antigen processing 2 (TAP2) G allele, initially discovered by us in a group of type 1 diabetes (insulin-dependent diabetes mellitus) patients living on Reunion Island, HLA TAP2 typing was performed using the polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) method in type 1 diabetes patients and unrelated healthy controls of three different ethnic groups (Caucasians, Indians and black Africans from Senegal and Mauritius). The comparison of TAP2 allele frequencies in controls showed significant racial (ethnic) differences. The TAP2*0101 and TAP2 C alleles were increased, respectively, in the Caucasian (50% in Caucasians vs. 40% in other groups) and Senegalese (27% in Senegalese vs. 10% in other groups) populations. In comparison with Caucasians, the TAP2*0201 variant was significantly increased in the Indian population and decreased in the Senegalese black population. In addition, the TAP2 G allele was observed in the two African populations studied but not in the Caucasian or Indian population. This observation is consistent with the view that this allele is restricted to populations of African origin. In addition, we have determined the large extended haplotype DQA1-DQB1-DRB1 associated with TAP2 G. We found that this allele is preferentially associated with the large conserved haplotype HLA DQA1*0501-DQB1*0201-DRB1*0301.