Diversity of HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes in Kazakhstani Tatar population and genetic relatedness to other populations.

BACKGROUND: Kazakhstan is a transcontinental former Soviet Union republic whose present-day population comprises more than 100 ethnic groups. Insofar as Human Leukocyte Antigen (HLA) genotyping is useful for anthropological studies, data on the HLA profile of Kazakhstani Tatars are lacking. OBJECTIVE: We extend our earlier findings on the unique HLA profile of distinct Kazakhstani populations by examining HLA class I and class II loci in Kazakhstani (Volga) Tatar minority population and its relatedness to those of bordering and worldwide communities. METHODS: HLA class I and class II genotypes of the Kazakhstan Tatar minority were analyzed by PCR-SSP and were compared to neighboring populations using Neighbor-Joining (NJ) trees and standard genetic distances (SGD) analysis. RESULTS: In total, 132 HLA alleles were identified in a sample of 103 Kazakhstani Tatars, of which HLA-A*02:01 (20.1 %), -B*07:02 (12.1 %), -C*07:02 (12.7 %), -DRB1*07:01 (18.1 %), and -DQB1*02:01 (19.6 %) were the most frequent. The most frequent two-locus haplotypes were B*07:02 âˆ¼ C*07:02 (10.6 %) B*07:02 âˆ¼ DRB1*15:01 (06.1 %), B*07:02 âˆ¼ DQB1*06:02 (07.1 %), and DRB1*15:01 âˆ¼ DQB1*06:02 (11.6 %). CONCLUSIONS: Considering historical data, the close relatedness of Kazakhstani Tatars to European Russians (including Russian Tatars) suggests that Kazakhstani Tatars may be Russian Tatars, who originated from the Volga region, following their massive migrations to central Asia.

Analysis of the Origin of Emiratis as Inferred from a Family Study Based on HLA-A, -C, -B, -DRB1, and -DQB1 Genes.

In this study, we investigated HLA class I and class II allele and haplotype frequencies in Emiratis and compared them to those of Asian, Mediterranean, and Sub-Saharan African populations. METHODS: Two-hundred unrelated Emirati parents of patients selected for bone marrow transplantation were genotyped for HLA class I (A, B, C) and class II (DRB1, DQB1) genes using reverse sequence specific oligonucleotide bead-based multiplexing. HLA haplotypes were assigned with certainty by segregation (pedigree) analysis, and haplotype frequencies were obtained by direct counting. HLA class I and class II frequencies in Emiratis were compared to data from other populations using standard genetic distances (SGD), Neighbor-Joining (NJ) phylogenetic dendrograms, and correspondence analysis. RESULTS: The studied HLA loci were in Hardy-Weinberg Equilibrium. We identified 17 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1, and 5 HLA-DQB1 alleles, of which HLA-A*02 (22.2%), -B*51 (19.5%), -C*07 (20.0%), -DRB1*03 (22.2%), and -DQB1*02 (32.8%) were the most frequent allele lineages. DRB1*03~DQB1*02 (21.2%), DRB1*16~DQB1*05 (17.3%), B*35~C*04 (11.7%), B*08~DRB1*03 (9.7%), A*02~B*51 (7.5%), and A*26~C*07~B*08~DRB1*03~DQB1*02 (4.2%) were the most frequent two- and five-locus HLA haplotypes. Correspondence analysis and dendrograms showed that Emiratis were clustered with the Arabian Peninsula populations (Saudis, Omanis and Kuwaitis), West Mediterranean populations (North Africans, Iberians) and Pakistanis, but were distant from East Mediterranean (Turks, Albanians, Greek), Levantine (Syrians, Palestinians, Lebanese), Iranian, Iraqi Kurdish, and Sub-Saharan populations. CONCLUSIONS: Emiratis were closely related to Arabian Peninsula populations, West Mediterranean populations and Pakistanis. However, the contribution of East Mediterranean, Levantine Arab, Iranian, and Sub-Saharan populations to the Emiratis' gene pool appears to be minor.

HLA allele and haplotype frequencies in Kazakhstani Russians and their relationship with other populations.

HLA class I and class II genotypes from 947 Kazakhstani individuals of Russian origin were analyzed for investigating their most likely origin. The results were compared with similar data from other Russians (East and West), and also Worldwide populations, using standard genetic distances, neighbor-joining dendrograms, correspondence and haplotype analysis. Of the five HLA loci analyzed (HLA-A, HLA-C, HLA-B, HLA-DRB1, and HLA-DQB1) genotyped, 216 HLA alleles were identified. The most frequent alleles were A*02:01 (26.5%), B*07:02 (11.1%), C*04:01 (13.5%) and C*06:02 (12.1%), DRB1*07:01 (13.8%) and DRB1*15:01 (12.2%), and DQB1*03:01 (19.7%). Significant linkage disequilibrium was noted between all HLA pairs. DRB1*15:01 ~ DQB1*06:02 (10.5%), B*07:02 ~ C*07:02 (10.0%), B*07:02 ~ DRB1*15:01 (6.3%), and A*01:01 ~ B*08:01 (4.5%) were the most frequent two-locus haplotypes identified. Subsequent analyses showed that Kazakhstani Russians were closely related to West Russia-residing populations (Northwest Slavic, Vologda, Chelyabinsk, Moscow), East Europeans (Belarus Brest, Ukraine, Poland) and Scandinavians (Swedish, Finns), but distinct from East Russia-residing populations (Tuvians, Siberians from Chukotka, Kamchatka, and Ulchi) and East Mediterraneans (Levantines, Turks, North Macedonians, Albanians), and East Asians (Koreans, Japanese, Taiwanese, Mongolians). These results are in accordance with historical data indicating that the Russians of central Asia originate mainly from European Russia during the migratory flow of 18th and 19th centuries.

HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in Lebanese and their relatedness to neighboring and distant populations.

BACKGROUND: This study examined the origin of present-day Lebanese using high-resolution HLA class I and class II allele and haplotype distributions. The study subjects comprised 152 unrelated individuals, and their HLA class I and class II alleles and two-locus and five-locus haplotypes were compared with those of neighboring and distant communities using genetic distances, neighbor-joining dendrograms, correspondence, and haplotype analyses. HLA class I (A, B, C) and class II (DRB1, DQB1) were genotyped at a high-resolution level by PCR-SSP. RESULTS: In total, 76 alleles across the five HLA loci were detected: A*03:01 (17.1%), A*24:02 (16.5%), B*35:01 (25.7%), C*04:01 (25.3%), and C*07:01 (20.7%) were the most frequent class I alleles, while DRB1*11:01 (34.2%) and DQB1*03:01 (43.8%) were the most frequent class II alleles. All pairs of HLA loci were in significant linkage disequilibrium. The most frequent two-locus haplotypes recorded were DRB1*11:01 ~ DQB1*03:01 (30.9%), B*35:01-C*04:01 (20.7%), B*35:01 ~ DRB1*11:01 (13.8%), and A*24:02 ~ B*35:01 (10.3%). Lebanese appear to be closely related to East Mediterranean communities such as Levantines (Palestinians, Syrians, and Jordanians), Turks, Macedonians, and Albanians. However, Lebanese appear to be distinct from North African, Iberian, and Sub-Saharan communities. CONCLUSIONS: Collectively, this indicates a limited genetic contribution of Arabic-speaking populations (from North Africa or the Arabian Peninsula) and Sub-Saharan communities to the present-day Lebanese gene pool. This confirms the notion that Lebanese population are of mixed East Mediterranean and Asian origin, with a marked European component.

Distribution of HLA-A, -C, -B, -DRB1, and -DQB1 polymorphisms in the Korean minority in Kazakhstan, and relatedness to neighboring and distant populations.

BACKGROUND: Among the 125 ethnicities and linguistic groups in Kazakhstan, Koreans represent the eighth minority numerically. HLA class I and class II allele frequencies and extended haplotypes were studied for the first time and were compared to related and distant populations worldwide. METHODS: HLA class I (A, B, C) and class II (DRB1, DQB1) profile was investigated in Kazakhstani Koreans, and were compared to other populations using standard genetic distances (SGD), neighbor-joining dendrograms, correspondence, and haplotype analysis. RESULTS: One hundred and thirty-one HLA alleles were identified in Koreans living in Kazakhstan, with A*02:01 (23.08%), B*35:01 (8.24%), C*01:02 (15.38%), DRB1*08:03 (9.89%), and DQB1*03:01 (21.98%) being the most frequent alleles. A*03:01 âˆ¼ B*07:02 (3.85%), B*08:01 âˆ¼ DRB1*03:01 (3.85%), B*07:02 âˆ¼ C*07:02 (7.14%), and DRB1*08:03 âˆ¼ DQB1*06:01 (9.34%) were the most frequent two-locus haplotypes, while A*02:01 âˆ¼ B*18:01 âˆ¼ C*07:01 âˆ¼ DRB1*11:04 âˆ¼ DQB1*03:01 and A*33:03 âˆ¼ B*44:03 âˆ¼ C*14:03 âˆ¼ DRB1*13:02 âˆ¼ DQB1*06:04 (2.2% each) were the most frequent five-locus haplotypes. CONCLUSION: Korean minority in Kazakhstan was closely related to East Asians, including Mongolians (SGD, 0.044), Tuvans (East Siberia; SGD, 0.081), Burayts (Siberia; SGD, 0.094), but distant from East Mediterranean such as Lebanese (SGD, 0.367), Greek (SGD, 0.377), and Saudi (SGD, 0.414), and most Siberians (SGD, 0.473-0.699). This relatedness could be mainly attributed to massive migration of Koryo Saram to Kazakhstan in the 20th century.

Origin of the Ukrainian minority of Kazakhstan as inferred from HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes distribution.

The present-day population of Kazakhstan comprises more than 100 ethnic and linguistic groups, of which Ukrainians rates numerically as the fourth, following native Kazakhs, Russians, and Uzbeks. We investigated the HLA profile of Kazakhstani Ukrainians and compared them with those of other populations by applying genetic distances, correspondence analysis, admixture, and haplotype examination. Of the 128 HLA alleles identified, A*02:01 (28.64%), B*07:02 (9.71%), B*13:02 (9.71%), C*06:02 (15.05%), DRB1*07:01 (15.20%), and DQB1*03:01 (24.76%) were the utmost common alleles. The most common 2-locus haplotypes identified were A*02:01 ~ B*13:02 (6.66%), B*13:02 ~ DRB1*07:01 (6.57%), B*13:02 ~ C*06:02 (10.10%), and DRB1*01:01 ~ DQB1*05:01 (12.12%), while A*02:01 ~ B*13:02 ~ C*06:02 ~ DRB1*07:01 ~ DQB1*02:01 were the most frequent five-locus haplotype (4.04%) in Kazakhstani Ukrainians. Comparative analysis revealed that Ukrainians of Kazakhstan are closely related to Eastern Europeans (included Ukrainians), and European Russians, but distant from Asian populations. This supports the historical notion that Kazakhstani Ukrainians originated from Ukraine, following their massive migrations to central Asia in the 18th-20th centuries.

Distribution of HLA Class I and Class II alleles and haplotypes in German and Uzbek minorities in Kazakhstan, and relationship to other populations.

HLA profiles of German and Uzbek minorities in Kazakhstan were analyzed and were compared with other populations. In total, 107 and 119 HLA alleles were identified in Germans and Uzbeks, respectively. A*02:01 (25.49%), B*07:02 (9.80%), B*08:01 (9.80%), C*07:02 (13.46%), DRB1*07:01 (21.57%), and DQB1*03:01 (25%) were frequent among Germans, while A*02:01 (17.86%), B*07:02 (8.33%), C*04:01 (15%), DRB1*07:01 (13.09%), and DQB1*03:01 (20%) were common alleles in Uzbeks. A*03:01 ~ B*07:02 ~ C*07:02 ~ DRB1*15:01 ~ DQB1*06:02 (6%) and A*24:02 ~ B*38:01 ~ C*12:03 ~ DRB1*14:01 ~ DQB1*05:03 (3.75%) were the most frequent five-locus haplotypes in Germans and Uzbeks, respectively. Germans of Kazakhstan are genetically related to European Russians, Germans and Eastern Europeans, suggesting their European Russia (Volga Region) origin following their 19th century migration to central Asia. Uzbeks, likely indigenous, were genetically close to Eastern Russians, Europeans, and Asians.

HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies and phylogenetic analysis of Bahraini population.

The origin of Arab-speaking population is classified according to their geographical location, ethnic background, and historical influx of nearby and distant populations. Data on HLA class I and class II loci in (Arabian Peninsula) Bahraini population are lacking. We analyzed HLA genetic profile of Bahrainis with neighboring communities, and with Levantines, North Africans, Sub-Saharans, Europeans, and Asians, using genetic distances, neighbor-joining dendrograms, correspondence and haplotype analysis. HLA class I and class II genotyping were done by high resolution PCR-SSP in 175 Bahraini subjects. In total, 19 HLA-A, 33 HLA-B, 15 HLA-C, 14 DRB1 and 7 DQB1 alleles were identified. The most common class I alleles were A*02:01:01 (18.3%), A*01:01:01(15.4%), B*35:01:02 (12.9%), C*12:01:01 (15.1%), and C*04:01:01 (14.9%), while DRB1*03:01:01 (18.0%), DQB1*02:01:01 (29.1%), and DQB1*05:01:01 (24.9%) were the most frequent class II alleles. Significant linkage disequilibrium was seen between all HLA loci pairs. DRB1*03:01:01-DQB1*02:01:01 (15.18%) was the most frequent two-locus haplotype. Significant negative Fnd values were observed, indicating balancing selection at studied loci. Bahrainis appear to be related to Western Mediterranean (North Africans, Iberians and French), but relatively distinct from Levantines (Palestinians, Lebanese, and Jordanians) and Sub-Saharans. This indicates limited genetic contribution of Levantine Arabs and Sub-Saharans to the Bahraini gene pool.

Maternal HLA-DR, HLA-DQ, and HLA-DP loci are linked with altered risk of recurrent pregnancy loss in Lebanese women: A case-control study.

PROBLEM: We investigated the association between idiopathic recurrent pregnancy loss (RPL) and HLA-DPB1, HLA-DQB1, and HLA-DRB1 alleles and DPB1-DQB1-DRB1 haplotypes. METHOD OF STUDY: Case-control retrospective study involved 93 Lebanese women with unexplained RPL, and 113 multiparous Lebanese women with two or more successful pregnancies, and no miscarriages who served as controls. DPB1, DQB1, and DRB1 genotyping was performed by PCR-SSP. RESULTS: Expected and observed DRB1, DQB1, and DPB1 frequencies were comparable, and HLA genotype frequencies were in Hardy-Weinberg equilibrium. Significantly higher frequencies of DRB1*04:01:01 and DRB1*08:01:01, and decreased DRB1*07:01:01 frequency were seen in RPL cases than in controls. On the other hand, the distribution of DQB1 alleles was comparable between cases and control groups. Significantly lower frequencies of DPB1*04:01:01 and DPB1*14:01:01 were seen in women with RPL than control subjects. While the frequency DPB1*02:01:01 was markedly higher in RPL cases than in controls, the difference was not significant. DPB1-DQB1-DRB1 haplotype analysis identified haplotype DPB1*04:01:01-DQB1*03:02:01-DRB1*04:01:01 to be positively associated, while haplotype DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 to be negatively associated with RPL. Of these two haplotypes, only DPB1*04:01:01-DQB1*02:01:01-DRB1*07:01:01 remained significant after correction for multiple tests (Pc  = .0008). CONCLUSION: Our results confirm an association of select DRB1 and DPB1 alleles with RPL in Lebanese women, and the first to identify DPB1-DQB1-DRB1 linked with altered RPL susceptibility, further highlighting the immunological/inflammatory nature of RPL.

HLA Class II Allele and Haplotype Diversity in Libyans and Their Genetic Relationships with Other Populations.

Background: Libya witnessed the succession of many civilizations and ethnic groups throughout history, thereby questioning the origin of present-day Libyans. Indeed, they were considered Africans given the geographical position of the country, Arabs at the cultural level, and Berbers because of the notable presence of Berber tribes. Genetic anthropology studies investigating the origin of Libyans were rarely reported, and thus little was known about the population structure of current Libyans, particularly at autosomic markers level. Methods: We examined HLA class II (DRB1, DQB1) gene profiles of 101 unrelated Libyans, and compared them with Arab-speaking communities and with Sub-Saharan and Mediterranean populations using Neighbour-Joining dendrograms, genetic distances, correspondence, and haplotype analysis. Results: Of the 42 DRB1 alleles identified, DRB1*07:01 (14.36%), DRB1*03:01 (12.38%) were the most frequent, while DQB1*02:01 (24.17%), DQB1*02:02 (13.86%), and DQB1*03:01 (12.38%) were the most frequent of the 17 DQB1 alleles detected. DRB1*03:01-DQB1*02:01 (6.93%), DRB1*07:01-DQB1*02:02 (4.45%), and DRB1*04:03-DQB1*03:02 (3.46%) were the most frequent DRB1-DQB1 haplotypes. Conclusion: Libyans appear to be closely related to North Africans, Saudis, and Iberians, but distinct from Levantine Arabs, East Mediterraneans, and Sub-Saharan Africans. This indicates limited genetic contribution of Levantine Arabs and Sub-Saharans on the makeup of Libyan gene pool. Our study confirmed genetic heterogeneity among Arab populations, with three identified groups. The first comprises North Africans, Saudis, and Kuwaitis who were related to Iberians and West Mediterraneans, while the second consists of Levantine Arabs who were close to East Mediterraneans, and the third contained Sudanese and Comorians, with a close relatedness to Sub-Saharans.

Association of HLA Class II Alleles and Haplotypes with Type 1 Diabetes in Tunisian Arabs.

The molecular association of HLA class II with type 1 diabetes (T1DM) was investigated in Tunisian Arabs using 3 kinds of analyses. The first was a case-control association study, using Relative Predispositional Effects method, involved 137 T1DM cases and 258 control subjects. The second was family-based association-linkage study, using Transmission Disequilibrium Test, and covering 50 Tunisian families comprising 73 T1DM patients and 100 parents. The third was a wide correlation study between 4 DRB1 alleles (DRB1*03, *04, *11, *15) and T1DM in 52 countries, using Spearman's Rho. Results from Case-control and family-based association studies showed that DRB1*03 and DRB1*04 alleles predispose to T1DM in Tunisian Arabs. Conversely, only DRB1*11 was protective for T1DM. DRB1*04-DQB1*03 haplotype was consistently associated positively with T1DM; DRB1*03/DRB1*04 genotype had the highest risk of T1DM development. Compared to DRB1*03, HLA-DRB1*04 was associated with higher T1DM incidence. Thus, the contribution of HLA class II to T1DM genetic susceptibility must be evaluated with regards to specific HLA alleles, genotypes, and haplotypes, and also ethnic and racial background.

Association of HLA-DRB1 and -DQB1 alleles with type 1 (autoimmune) diabetes in African Arabs: systematic review and meta-analysis.

Several studies confirmed the association of HLA-DRB1 and -DQB1 alleles with altered risk of type 1 diabetes (T1D). However, data from individual studies based on small sample sizes yielded often conflicting findings in African Arabs. This is a systematic review and meta-analysis aimed at comprehensively evaluating this association with T1D, using molecular HLA data. Relevant studies were identified through systemic search of Medline/PubMed, Cochrane, Science Direct, ResearchGate, and EMBASE databases. Statistical analysis was carried out using RevMan, and Comprehensive Meta-analysis programs. Given the heterogeneity of African Arabs, we also performed subgroup analysis according to ethnicity. Analysis of sensitivity, heterogeneity, and publication bias were performed to validate the outcome of the findings. This meta-analysis included 862 T1DM cases, along with 1,390 normoglycemic control, and comprised ten comparisons. Our study indicates that DRB1*03 (OR = 2.86), DRB1*04 (OR = 2.78), and DQB1*02 (OR = 2.29), are positively associated with increased risk of T1DM, while DRB1*07 (OR = 0.48), DRB1*11 (OR = 0.20), DRB1*13 (OR = 0.47), DRB1*15 (OR = 0.30), DQB1*05 (OR = 0.39), and DQB1*06 (OR = 0.27) were negatively associated with T1D, suggesting a protective role against T1D. This meta-analysis was characterized by low heterogeneity, sensitivity, and publication bias, indicating the robustness and reliability of the results. BACKGROUND: Several studies confirmed the association of HLA-DRB1 and -DQB1 alleles with altered risk of type 1 diabetes (T1D). However, data from individual studies based on small sample sizes yielded often conflicting findings in African Arabs. This is a systematic review and meta-analysis aimed at comprehensively evaluating this association with T1D, using molecular HLA data. METHODS: Relevant studies were identified through systemic search of Medline/PubMed, Cochrane, Science Direct, ResearchGate, and EMBASE databases. Statistical analysis was carried out using Revman, and Comprehensive Meta-analysis programs. Given the heterogeneity of African Arabs, we also performed subgroup analysis according to ethnicity. Analysis of sensitivity, heterogeneity, and pub¬lication bias were performed to validate the outcome of the findings. This meta-analysis included 862 T1DM cases, along with 1,390 normoglycemic control, and comprised ten comparisons. RESULTS: Our study indicates that DRB1*03 (OR = 2.86), DRB1*04 (OR = 2.78), and DQB1*02 (OR = 2.29), are positively associated with increased risk of T1DM, while DRB1*07 (OR = 0.48), DRB1*11 (OR = 0.20), DRB1*13 (OR = 0.47), DRB1*15 (OR = 0.30), DQB1*05 (OR = 0.39), and DQB1*06 (OR = 0.27) were negatively associated with T1D, suggesting a protective role against T1D. CONCLUSION: This meta-analysis was characterized by low heterogeneity, sensitivity, and publication bias, indicating the robustness and reliability of the results.

The genetic heterogeneity of Arab populations as inferred from HLA genes.

This is the first genetic anthropology study on Arabs in MENA (Middle East and North Africa) region. The present meta-analysis included 100 populations from 36 Arab and non-Arab communities, comprising 16,006 individuals, and evaluates the genetic profile of Arabs using HLA class I (A, B) and class II (DRB1, DQB1) genes. A total of 56 Arab populations comprising 10,283 individuals were selected from several databases, and were compared with 44 Mediterranean, Asian, and sub-Saharan populations. The most frequent alleles in Arabs are A*01, A*02, B*35, B*51, DRB1*03:01, DRB1*07:01, DQB1*02:01, and DQB1*03:01, while DRB1*03:01-DQB1*02:01 and DRB1*07:01-DQB1*02:02 are the most frequent class II haplotypes. Dendrograms, correspondence analyses, genetic distances, and haplotype analysis indicate that Arabs could be stratified into four groups. The first consists of North Africans (Algerians, Tunisians, Moroccans, and Libyans), and the first Arabian Peninsula cluster (Saudis, Kuwaitis, and Yemenis), who appear to be related to Western Mediterraneans, including Iberians; this might be explained for a massive migration into these areas when Sahara underwent a relatively rapid desiccation, starting about 10,000 years BC. The second includes Levantine Arabs (Palestinians, Jordanians, Lebanese, and Syrians), along with Iraqi and Egyptians, who are related to Eastern Mediterraneans. The third comprises Sudanese and Comorians, who tend to cluster with Sub-Saharans. The fourth comprises the second Arabian Peninsula cluster, made up of Omanis, Emiratis, and Bahrainis. It is noteworthy that the two large minorities (Berbers and Kurds) are indigenous (autochthonous), and are not genetically different from "host" and neighboring populations. In conclusion, this study confirmed high genetic heterogeneity among present-day Arabs, and especially those of the Arabian Peninsula.

Anthropological analysis of Tunisian populations as inferred from HLA class I and class II genetic diversity: A meta-analysis.

Despite their importance, anthropological meta-analyses which allow for comprehensive evaluation of the relationships of a given population were rare. This meta-analysis evaluates the origin of Tunisians using polymorphic profile of HLA class I (A, B), and class II (DRB1, DQB1) genes, in historical, social and cultural context, and is the only analysis in the Middle East-North Africa (MENA) region. A total of 20 eligible populations were selected from several databases, and included representing 2553 Tunisian individuals, who were compared with Mediterranean and sub-Saharan populations. In total, 204 HLA alleles were detected in Tunisians, which comprised 54 HLA-A, 76 HLA-B, 50 DRB1, and 24 DQB1 alleles. The most frequent alleles were A*02:01(24.72%) in Berbers of Zrawa, B*50:01 (13.90.11%) in Tunisian-So, DRB1*07:01 (28.66%) in Ghannouchians, and DQB1*02:01 (42.79%) in Tunisians-H. The A, B, DRB, and DQB1 genotypes of 420 individuals were further subjected to a selection study. Despite the relatively large sample size, the loci depicted non-significant negative Fnd values, an indication of overall trend to balancing selection or gene flow. Except for Berbers of Djerba, dendrograms, correspondence analyses, genetic distances and haplotype analysis demonstrated the close relatedness of Berbers, Southern and Northern Tunisians, and strong relatedness was evident to Western Mediterranean, North African and Iberian populations, but not Sub-Saharans and Eastern Mediterranean populations, including Arabs. Collectively, this suggests that the contribution of Arabs and sub-Saharans to the present Tunisian gene pool is low. In addition, all Mediterranean populations depict a typical Mediterranean substratum, except for Greeks.

The investigation of the origin of Southern Tunisians using HLA genes.

The south of Tunisia is characterized by marked ethnic diversity, highlighted by the coexistence of native Berbers with Blacks, Jews and Arab-speaking populations. Despite this heterogeneity, genetic anthropology studies investigating the origin of current Southern Tunisians were rarely reported. We examined human leukocyte antigen (HLA) class I (A, B) and class II (DRB1, DQB1) gene profiles of 250 unrelated Southern Tunisians, and compared them with those of Arab-speaking communities, along with Mediterranean and sub-Sahara African populations using genetic distances, neighbor-joining dendrograms, correspondence and haplotype analysis. In total, 137 HLA alleles were detected, which comprised 32 HLA-A, 52 HLA-B, 32 DRB1 and 21 DQB1 alleles. The most frequent alleles were HLA-A*02:01(18.02%), HLA-B*50:01 (9.11%), HLA-DRB1*07:01 (22.06%) and HLA-DQB1*02:01 (17.21%). All pairs of HLA loci show significant linkage disequilibrium. The four loci depict negative Fnd (the normalized deviate of the homozygosity) values indicating an overall trend to balancing selection. Southern Tunisians appear to be closely related to others Tunisian populations including Berbers, North Africans and Iberians. On the contrary, Southern Tunisians were distinct from Palestinian, Lebanese and Jordanian Middle Eastern Arab-speaking population, despite the deep Arab incursions and Arabization that affected Southern Tunisia. In addition, Southern Tunisians were distant from many sub-Saharan communities, evidenced by genetic distance analysis. Collectively, this indicates a limited genetic contribution of Arab invasion and Black caravans on the makeup of Southern Tunisian gene pool.

HLA Class I and Class II Alleles and Haplotypes Confirm the Berber Origin of the Present Day Tunisian Population.

In view of its distinct geographical location and relatively small area, Tunisia witnessed the presence of many civilizations and ethnic groups throughout history, thereby questioning the origin of present-day Tunisian population. We investigated HLA class I and class II gene profiles in Tunisians, and compared this profile with those of Mediterranean and Sub-Sahara African populations. A total of 376 unrelated Tunisian individuals of both genders were genotyped for HLA class I (A, B) and class II (DRB1, DQB1), using reverse dot-blot hybridization (PCR-SSO) method. Statistical analysis was performed using Arlequin software. Phylogenetic trees were constructed by DISPAN software, and correspondence analysis was carried out by VISTA software. One hundred fifty-three HLA alleles were identified in the studied sample, which comprised 41, 50, 40 and 22 alleles at HLA-A,-B,-DRB1 and -DQB1 loci, respectively. The most frequent alleles were HLA-A*02:01 (16.76%), HLA-B*44:02/03 (17.82%), HLA-DRB1*07:01 (19.02%), and HLA-DQB1*03:01 (17.95%). Four-locus haplotype analysis identified HLA-A*02:01-B*50:01-DRB1*07:01-DQB1*02:02 (2.2%) as the common haplotype in Tunisians. Compared to other nearby populations, Tunisians appear to be genetically related to Western Mediterranean population, in particular North Africans and Berbers. In conclusion, HLA genotype results indicate that Tunisians are related to present-day North Africans, Berbers and to Iberians, but not to Eastern Arabs (Palestinians, Jordanians and Lebanese). This suggests that the genetic contribution of Arab invasion of 7th-11th century A.D. had little impact of the North African gene pool.