Distribution Of HLA Alleles Research Articles

Association of Human Leukocyte Antigens Class I and II Variants with Susceptibility to Pulmonary Tuberculosis in a Caucasian Population from Northern Spain

Background: Susceptibility to TB seems to be multifactorial, and the development of active disease is probably the result of complex interactions between the host and pathogen, influenced by environmental and genetic factors. The Human Leukocyte Antigen system or HLA seems to be one of these factors. Differences in the distribution of HLA alleles and haplotypes have been found worldwide with conflicting results among different populations and few data concerning Caucasian populations have been reported. Methods: Distribution of HLA class I and class II alleles was evaluated in 160 Spanish patients with pulmonary tuberculosis, all of them HIV negative, 109 latently infected individuals, and in 262 healthy individuals. All the subjects included in the study belonged to the same geographical area (Cantabria, northern Spain). Results: HLA-A*02 was found to be significantly more frequent in the latently infected group compared with the control group (34.86% versus 25.19%, p=0.009, OR 0.63 IC95% 0.45-0.89) and with patients with pulmonary tuberculosis (34.86% versus 25.79%, p=0.03, OR 0.65 IC95% 0.45-0.94). HLA-C*08 was found to be significantly more frequent in pulmonary tuberculosis patients compared with the control group (9.69% versus 5.34%, p=0.02, OR 1.91 IC95% 1.12-3.25). HLA-DRB1*04 was found to be significantly more frequent in pulmonary tuberculosis patients compared with the control group (17.19% versus 11.83%, p=0.037, OR 1.55 IC95% 1.04-2.29). Finally, HLA-DRB1*07 was found to be significantly more frequent in healthy and latently infected individuals compared with patients with pulmonary tuberculosis (19.66% & 21.10% versus 13.75%, p=0.036 & 0.034, OR 0.65 & 0.60 IC95% 0.44-0.96 & 0.38-0.94 respectively). The only haplotype which was significantly more frequent in pulmonary tuberculosis patients versus healthy individuals was the DRB1*04-DQA1*03-DQB1*03 extended three locus haplotype (p=0.04, OR 1.53 IC95% 1.03-2.72). All these differences disappeared after statistical correction for multiple comparisons. Conclusion: Although there were no significant differences in HLA alleles distribution among the three groups after statistical correction, there seems to be a slight trend of certain alleles in conferring protection against or susceptibility to pulmonary tuberculosis, at least in our population.

The significance of HLA typing in transplantation

Although genetic admixture has recently occurred among different ethnic groups with the increased rates of migration to big cities, information about HLA allele distribution in different ethnic groups in Iran may still be helpful to improve the selection of transplantation donor candidates from certain ethnic groups which are genetically closer to the recipient. Because the data reported by Einollahi et al. reflect a large HLA disparity among Iranian kidney recipients, any improvement could play a small yet important role in organ transplantation.

Distribution of HLA-A, -B and -DRB1 Genes and Haplotypes in the Tujia Population Living in the Wufeng Region of Hubei Province, China

BackgroundThe distribution of HLA alleles and haplotypes varies widely between different ethnic populations and geographic areas. Before any genetic marker can be used in a disease-associated study it is therefore essential to investigate allelic frequencies and establish a genetic database.Methodology/Principal FindingsThis is the first report of HLA typing in the Tujia group using the Luminex HLA-SSO method HLA–A, –B and -DRB1 allelic distributions were determined in 124 unrelated healthy Tujia individuals, and haplotypic frequencies and linkage disequilibrium parameters were estimated using the maximum-likelihood method. In total 10 alleles were detected at the HLA–A locus, 21 alleles at the HLA–B locus and 14 alleles at the HLA-DRB1 locus. The most frequently observed alleles in the HLA-I group were HLA–A*02 (35.48%), A*11 (28.23%), A*24 (15.73%); HLA–B*40 (25.00%), B*46 (16.13%), and B*15 (15.73%). Among HLA-DRB1 alleles, high frequencies of HLA-DRB1*09 (25.81%) were observed, followed by HLA-DRB1*15 (12.9%), and DRB1*12 (10.89%). The two-locus haplotypes at the highest frequency were A*02–B*46A (8.47%), followed by A*11–B*40 (7.66%), A*02–B*40 (8.87%), A*11–B*15 (6.45%), A*02–B*15 (6.05%), B*40–DRB1*09 (9.27%) and B*46–DRB1*09 (6.45%). The most common three-locus haplotypes found in the Tujia population were A*02–B*46–DRB1*09 (4.84%) and A*02–B*40–DRB1*09 (4.03%). Fourteen two-loci haplotypes had significant linkage disequilibrium. Construction of a neighbor-joining phylogenetic tree and principal component analysis using the allelic frequencies at HLA-A was performed to compare the Tujia group and twelve other previously reported populations. The Tujia population in the Wufeng of Hubei Province had the closest genetic relationship with the central Han population, and then to the Shui, the Miao, the southern Han and the northern Han ethnic groups.Conclusions/SignificanceThese results will become a valuable source of data for tracing population migration, planning clinical organ transplantation, carrying out HLA-linked disease-associated studies and forensic identification.

Pilot Study of the Association between the HLA Region and Testicular Carcinoma among Croatian Patients

Objectives: To analyze the distribution of HLA alleles and HLA microsatellite alleles in Croatian patients with testicular carcinoma, compare it with that of healthy controls and investigate whether the polymorphism within the HLA region could be associated with the development of testicular cancer. Methods: Genomic DNA was isolated from the peripheral blood of 24 patients with testicular germ cell tumors (TGCT). Patients and controls were typed for HLA class I and class II polymorphism by the PCR-SSO method. Nine HLA microsatellites were analyzed by PCR and electrophoresis in an automated sequencer. Results: No significant deviation in the distribution of frequencies at HLA class I alleles was observed between patients and controls. Among HLA class II alleles, a statistically significant increase in the frequency of the HLA-DPB1*1701 allele was found among patients. The frequency of the HLA-DRB1*07-DQA1*0201-DQB1*0202 haplotype was increased in patients in comparison to the controls. Analysis of HLA microsatellites showed an increased frequency of D6S291-3 allele (p_corr = 0.0455, OR = 3.05) among patients. Conclusions: The observed association of the disease and the DPB1*1701 allele as well as with the D6S291-3 allele suggests that this part of the HLA region might be involved in the pathogenesis of TGCT. Our data provide a basis for further studies about the correlation between the HLA region and testicular cancer.

HLA allele distributions and associations in a cohort of LTNPs from China

Background Various studies have shown that HLA polymorphisms are associated with susceptibility/resistance to HIV-1 infection, and therefore influence the rate of disease progression of HIV/AIDS in individuals of different ethnic backgrounds. Association of HLA with HIV/AIDS has been studied extensively within Caucasians and Africans. However, limited data are available from China. Methodology HIV Positive Samples were collected from the SM village in Henan province: SM Cohort. These subjects got infected in the early 90s after taking part in an illegal plasma donation scheme that became contaminated by HIV-1 infection. Our data show that they were infected by a single or a few closely related clade B strains. Control samples collected from a neighboring village. DNA was extracted, HLA-typing done and HLA analysis computed using Arlequin and SAS. Results

Clinical and Genetic Characteristics of Patients With Type 1 Diabetes Associated With Interferon Therapy

OBJECTIVEThis study clarified characteristics of interferon-associated type 1 diabetes.RESEARCH DESIGN AND METHODSThe study compared 12 patients with interferon-associated type 1 diabetes with 128 patients with type 1A diabetes with respect to clinical characteristics, and with 10 patients without diabetes despite interferon therapy and 136 normal controls with respect to HLA allele distributions.RESULTSPatients with interferon-associated type 1 diabetes retained higher levels of fasting serum C peptide as well as GAD65 antibodies than those with type 1A diabetes until 2 to 4 years after onset. HLA-A*2402 was increased among patients with interferon-associated type 1 diabetes compared with those without diabetes, despite interferon therapy (odds ratio [OR] 4.00 [95% CI 1.09–17.26]). The haplotype of DRB1*1302-DQA1*0102-DQB1*0604 was increased in these two groups combined compared with normal controls (OR 5.64 [95% CI 2.67–11.81]).CONCLUSIONSInterferon-associated type 1 diabetes is characterized clinically by high titers of GAD65 antibodies and preserved β-cell function, and genetically by addition of HLA-A*2402to DRB1*1302-DQA1*0102-DQB1*0604.

Allelic and Haplotypic Diversity of HLA-A, -B, -C, and -DRB1 Genes in Koreans Defined by High-resolution DNA Typing

In this study, we used high-resolution DNA typing to investigate the distribution of HLA alleles and haplotypes in Koreans. HLA-A, -B, -C, and -DRB1 alleles were genotyped at the allelic (4-digit) level in 474 healthy Koreans. HLA genotyping was performed in two steps. Initially, serologic typing or generic-level DNA typing was performed using the PCR-sequence-specific oligonucleotide method, and then allelic DNA typing (exons 2 and 3 for class I, and exon 2 for DRB1) was carried out using the PCR-single-strand conformation polymorphism method or sequence-based typing. HLA allele and haplotype frequencies and linkage disequilibrium values were calculated by the maximum likelihood method using a computer program developed for the 11th International Histocompatibility Workshop. A total of 21 HLA-A, 40 HLA-B, 22 HLA-C, and 29 HLA-DRB1 alleles were found in Koreans. The most frequent alleles in each locus with frequencies of ≥ 10% were, in decreasing order of frequency, as follows: A*24:02, A*02:01, A*33:03; B*51:01; C*01:02, C*03:03; and DRB1*09:01. The numbers of two- and three-locus haplotypes with frequencies of >0.5% were as follows: 44 A-C, 42 B-C, 51 A-B, 52 B-DRB1, 42 A-C-B, and 34 A-B-DRB1. Thirteen A-B-DRB1 haplotypes with frequencies of ≥ 1.0% comprised 26.0% of the total haplotypes. The six most common haplotypes were as follows: A*33:03-B*44:03-DRB1*13:02 (3.7%), A*33:03-B*44:03-DRB1*07:01 (3.0%), A*33:03-B*58:01-DRB1*13:02 (3.0%), A*24:02-B*07:02-DRB1*01:01 (2.8%), A*30:01-B*13:02-DRB1*07:01 (2.3%), and A*11:01-B*15:01-DRB1*04:06 (2.2%). The information obtained in this study can be used as basic data for Koreans in the fields of organ transplantation, disease association, and anthropologic studies.

Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients

BackgroundA strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping.Subjects and methodsIn this study we HLA typed a large patient population (n = 754) recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS) (n = 302) and those without (non-Löfgren's) (n = 452), and the majority of them were clinically classified into those with recovery within two years (resolving) and those with signs of disease for more than two years (non-resolving). PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366) served as controls.ResultsThere was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10-36). Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis) dominated over that of DRB1*15 (bad prognosis).ConclusionsWe found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.

Allele and Haplotype Frequencies of Human Leukocyte Antigen-A, -B, and -DR Loci in Koreans: DNA Typing of 1,500 Cord Blood Units

The HLA system is known to be the most polymorphic genetic system in human, and HLA allele and haplotype distribution varies widely among different ethnic groups. This study was performed to examine the frequencies of HLA alleles and haplotypes in Koreans. We examined HLA-A, -B, and -DR alleles at the serologic level in 1,500 cord blood units obtained from Koreans using the PCR-sequence specific oligonucleotide (SSO) method. Allele and haplotype frequencies were estimated by the maximum likelihood method using the computer program developed for the 11th International Histocompatibility Workshop. HLA alleles found in Koreans were 12 in A, 31 in B, and 13 in DR loci. Most frequent alleles with frequencies > or =10% in each locus in decreasing order of frequency were: A2, A24, A33, A11; B62; DR4, DR15, DR9, and DR13. Two-locus haplotypes with frequencies > or =0.1% were 104 A-B and 115 B-DR haplotypes, among which those with frequencies > or =1.0% showing significant positive linkage disequilibrium (P< or =0.001) were 21 A-B and 20 B-DR haplotypes. A total of 169 A-B-DR haplotypes with frequencies > or =0.1% were identified. The results were similar to those of a previous study in 1,600 Koreans, although some differences were noted in the distribution of some less frequent alleles or haplotypes with frequencies < or =0.5%. We provided the allele and haplotype frequencies of HLA-A, -B, and -DR in cord blood units of Korean ethnicity defined by a DNA typing method, which can be used as basic data on Koreans for organ transplantation and disease association studies.

Polymorphisme HLA et maladie de Behçet dans la population marocaine

Objectives We have study the various associations between Behçet disease and alleles HLA class I and II in Moroccan population. The distribution of HLA alleles involved in the disease is assessed according to clinical signs and sex. Patients and methods Patients suffering from Behçet's disease have been compared to healthy controls matched by age and ethnic origin. The HLA typing has been conducted by using microlymphocytotoxicity for the class I (A and B) and molecular biology (polymerase chain reaction-sequence specific primers) for the class II (DR and DQ). Results In addition to the allele B51, -A2, -B5102, -B58 and -B72 predispose to the Behçet's disease and the alleles A23, -A33, -B18, -B41 and -B49 have a negative correlation in our Moroccan patients. The alleles A2 and -B72 are specific to men, -A68 and -B58 to women, whereas -B51 and -B5102 are predisposing to the Behçet's disease of both genders. The allele B51 is related to the mucous manifestations, -B72 to the vascularitis manifestations and -B58 to the cutaneous manifestations. The haplotypes A2-B51 has a high positive correlation with this Behçet's disease. Concerning class II, none of the alleles DRB1* is implicated in the pathology even though the allele DQB1*02 ensures the patients’ protection. Conclusions The allele HLA-B51 shows a high positive correlation with the Behçet's disease. Other genetic factors seem to be implicated in susceptibility or protection against the disease.

Statistical resolution of ambiguous HLA typing data.

High-resolution HLA typing plays a central role in many areas of immunology, such as in identifying immunogenetic risk factors for disease, in studying how the genomes of pathogens evolve in response to immune selection pressures, and also in vaccine design, where identification of HLA-restricted epitopes may be used to guide the selection of vaccine immunogens. Perhaps one of the most immediate applications is in direct medical decisions concerning the matching of stem cell transplant donors to unrelated recipients. However, high-resolution HLA typing is frequently unavailable due to its high cost or the inability to re-type historical data. In this paper, we introduce and evaluate a method for statistical, in silico refinement of ambiguous and/or low-resolution HLA data. Our method, which requires an independent, high-resolution training data set drawn from the same population as the data to be refined, uses linkage disequilibrium in HLA haplotypes as well as four-digit allele frequency data to probabilistically refine HLA typings. Central to our approach is the use of haplotype inference. We introduce new methodology to this area, improving upon the Expectation-Maximization (EM)-based approaches currently used within the HLA community. Our improvements are achieved by using a parsimonious parameterization for haplotype distributions and by smoothing the maximum likelihood (ML) solution. These improvements make it possible to scale the refinement to a larger number of alleles and loci in a more computationally efficient and stable manner. We also show how to augment our method in order to incorporate ethnicity information (as HLA allele distributions vary widely according to race/ethnicity as well as geographic area), and demonstrate the potential utility of this experimentally. A tool based on our approach is freely available for research purposes at http://microsoft.com/science.

World distribution of HLA alleles and implications for disease.

The high level of polymorphism of the HLA system makes it useful for the study of diversity in different populations. However, its relationships with disease susceptibility, resistance and progression impose selective pressure on population frequencies that must be taken into consideration. These relationships allow useful studies on the genetic susceptibility to disease, which can be studied further and may provide us with another tool with which to examine the history of populations.

Cord blood stem cell transplantation. Why it is necessary to establish a Bulgarian cord blood bank?

The allogenic transplantation of hemopoietic stem cell from bone marrow and peripheral blood is limited due to the necessity to identify HLA matched donor within the family or in bone marrow donor registries. Although, more than 10 million donors are available worldwide, completely HLA matched donors could be found only for 75% of the patients. It is well known that transplantations of hematopoietic stem cell from cord blood are characterized with a lower risk of GvHD and therefore do not require so strict criteria for HLA matching, and less time for search of matched donor is needed. The necessity to establish a National cord blood bank in Bulgaria is emphasized further by the heterogeneity of HLA allele and haplotype distribution in the Bulgarian population. That could be explained by the ethnic diversity of the population. As a result some alleles are more frequent in Bulgarians compared to other populations. The organization, accreditation, and development of a strategy for a National cord blood bank will be discussed.

Origin of Tibeto-Burman speakers: Evidence from HLA allele distribution in Lisu and Nu inhabiting Yunnan of China

The issue about the origin of the Tibeto-Burman speaking ethnic groups (TBs) mostly residing in the Hengduan and Himalayan region in southwest China has been disputed for several decades. Based primarily on historical literatures and archaeologic findings the "Di-Qiang origin" hypothesis was proposed, in which the Tibeto-Burman speakers were thought to be descendants of the ancient Di-Qiang groups (DQs) who originated in northwest China. However, other evidence also challenge this hypothesis. In the present study, we investigate the distribution of HLA class I and class II genes in Lisu and Nu, two Tibeto-Burman-speaking ethnic groups, using a high-resolution polymerase chain reaction-sequencing-based typing method. Lisu and Nu share similar allele and haplotype frequencies of HLA class I and class II genes. Phylogenetic trees and principal component analysis based on HLA allele frequencies clearly indicated that Lisu and Nu clustered together with high bootstrap value, suggesting their close genetic relationship. The complicated genetic background of TBs was also revealed. The dendrogram based on HLA class II allelic frequencies demonstrated that East Asians clustered together and that four Tibeto-Burman-speaking ethnic groups (Naxi, Lahu, Lisu, and Nu) formed a clade clustering with southern East Asians (SEA), whereas another Tibeto-Burman speaker, Yi, integrated into the cluster of northern East Asians (NEA). Principal component analysis based on HLA class II allelic frequencies supported that TBs could be classified into two groups with Naxi, Lahu, Lisu and Nu scattering among SEA, while Yi locating close to NEA. A clear boundary between NEA and SEA was also observed in the principal component plot based on HLA class I allele frequencies and Lisu and Nu clustered into the SEA. In conclusion, our results provide evidences that not only DQs but also southwest aborigines may be ancestors of the TBs.

The distribution of HLA alleles revealed a founder effect in the geographically isolated Chinese population, Drung

The Drung ethnic minority is one of the smallest ethnic groups of China, geographically isolated by mountains and rivers. Before 1949, Drung society maintained many vestiges of the primitive commune system. The origin and migration of the Drung and their genetic background are still unknown because of limited records about this population. Here, we for the first time demonstrated the unique distribution of HLA alleles in the Drung by high-resolution sequence-based typing (SBT) method. Number of alleles detected is obviously less than expected and only a few alleles with a high homozygosity in each locus are predominant in this minority. The characteristics of HLA allele distribution in the Drung could reflect founder effects, suggesting the Drung probably descended from very few ancestors. The statistical analysis based on allele frequencies indicated that the Drung was an isolated ethnic group, but it also provided the clue that the Drung was genetically related to Chinese southwestern ethnic groups. Significant reduced allelic diversity and genetic isolate in the Drung make it an ideal homogeneous population and very useful model to study the evolution of HLA and the origin and migration of Chinese ethnic groups. The research paved a way to elucidate the genetic background of this mysterious minority and disease predisposition.

Celiac Disease Genetics: Current Concepts and Practical Applications

Celiac disease is a multifactorial disease with complex genetics. Both HLA and non-HLA genes contribute to the genetic component, but recent findings suggest that the importance of non-HLA genes might have been overestimated. No susceptibility genes other than HLA-DQ have yet been identified in celiac disease. In contrast to the meager knowledge regarding non-HLA genes, we have acquired a detailed understanding about which HLA genes are predisposing for disease, and how they are involved in the pathogenesis. This knowledge might pave the road for novel treatments for the disease. The role of HLA as a necessary, but not sufficient, genetic factor can moreover be used for diagnostic purposes to exclude a celiac disease diagnosis. The applicability of HLA genotyping is particularly useful for excluding celiac disease in family members or risk groups with fairly unbiased distribution of HLA alleles (ie, patients with Turner syndrome and patients with Down syndrome) and in patients with a clinical suspicion of celiac disease.

Autoimmune Studies and HLA Associations in SLE Patients from Mumbai

KEYWORDS SLE; autoimmune antibodies; HLA; organ involvement ABSTRACT To determine the autoimmune status and HLA allele distribution in SLE patients confirmed on serological and clinical grounds and compared with normal age matched ethnic control population from Mumbai. HLA A, B serological typing were carried out in 53 unrelated SLE patients and 110 healthy controls. Autoantibodies were detected by indirect immunofluorescence and ELISA techniques. The autoantibodies directed towards ANF, anti Sm, AHA were increased among the major organ involved patients while the antibodies like anti - dsDNA, anti - ssDNA, anti - nRNP, anti - SSA (Ro), anti - SSA (La) and RF were increased among the other patients with minor organ involvement. HLA A1, A2, and B27 alleles were positively associated, while HLA A19, and B15 alleles were negatively associated among the total SLE patients when compared to normal controls. It was further interesting to note that among the major organ involved severe patients A3, A28, and B7 where increased while A11, A19 and B17 were decreased. Among the minor organ involved patients it was A1, A2, A26, B5, B40 and B56 which were increased while A11, A28 and B7 were decreased. A significant twofold increase in the odds ratio for HLA A3, A28 and B27 alleles with increased Ro, La, Sm and ds DNA autoantibodies was observed when compared to controls. A significant twofold decrease in the odds ratio for HLA A19, A11, B7 and B15 alleles with decreased Ro, La, Sm and ds DNA autoantibodies was observed, when compared to normal controls suggesting the positive and negative associations of these HLA alleles among the SLE patients from Mumbai.

Population genetic relationships between Mediterranean populations determined by HLA allele distribution and a historic perspective.

HLA genes allele distribution has been studied in Mediterranean and sub-Saharan populations. Their relatedness has been tested by genetic distances, neighbour-joining dendrograms and correspondence analyses. The population genetic relationships have been compared with the history of the classical populations living in the area. A revision of the historic postulates would have to be undertaken, particularly in the cases when genetics and history are overtly discordant. HLA genomics shows that: 1) Greeks share an important part of their genetic pool with sub-Saharan Africans (Ethiopians and west Africans) also supported by Chr 7 Markers. The gene flow from Black Africa to Greece may have occurred in Pharaonic times or when Saharan people emigrated after the present hyperarid conditions were established (5000 years B.C.). 2) Turks (Anatolians) do not significantly differ from other Mediterraneans, indicating that while the Asians Turks carried out an invasion with cultural significance (language), it is not genetically detectable. 3) Kurds and Armenians are genetically very close to Turks and other Middle East populations. 4) There is no HLA genetic trace of the so called Aryan invasion, which has only been defined on doubtful linguistic bases. 5) Iberians, including Basques, are related to north-African Berbers. 6) Present-day Algerian and Moroccan urban and country people show an indistinguishable Berber HLA profile.

Distribution of HLA alleles in Portugal and Cabo Verde. Relationships with the slave trade route.

HLA-A, -B, and -DR frequencies were analysed in populations from Portugal and the Madeira and Cabo Verde Archipelagos, aiming to characterize their genetic composition. Portuguese settlers colonized both Archipelagos in the 15th and 16th centuries. Madeira received many sub-Saharan slaves to work in the sugar plantations, and Cabo Verde served as a pivotal market in the Atlantic slave trade and was populated by individuals coming from the Senegambia region of the West African coast. The population of Madeira shows the highest genetic diversity and the presence of alleles and haplotypes usually linked to sub-Saharan populations, the haplotypes accounting for 3.5% of the total. Cabo Verde presents typical markers acknowledged to be of European or Ibero-Mediterranean origin, thus revealing the admixture of European settlers with Sub-Saharan slaves. Altogether the number of European haplotypes reaches 15% of the total. The Portuguese population shows a perceivable and significant heterogeneity both in allele and haplotype frequencies, unveiling a differential input of peoples from different origins. A PCA of the populations studied, plus other relevant ones, clearly shows gene heterogeneity in mainland Portugal as well as the differences and relationships between these populations and Madeira and Cabo Verde.

Distribution of HLA alleles in Portugal and Cabo Verde. Relationships with the slave trade route

HLA‐A, ‐B, and ‐DR frequencies were analysed in populations from Portugal and the Madeira and Cabo Verde Archipelagos, aiming to characterize their genetic composition. Portuguese settlers colonized both Archipelagos in the 15th and 16th centuries. Madeira received many sub‐Saharan slaves to work in the sugar plantations, and Cabo Verde served as a pivotal market in the Atlantic slave trade and was populated by individuals coming from the Senegambia region of the West African coast. The population of Madeira shows the highest genetic diversity and the presence of alleles and haplotypes usually linked to sub‐Saharan populations, the haplotypes accounting for 3.5% of the total. Cabo Verde presents typical markers acknowledged to be of European or Ibero‐Mediterranean origin, thus revealing the admixture of European settlers with Sub‐Saharan slaves. Altogether the number of European haplotypes reaches 15% of the total. The Portuguese population shows a perceivable and significant heterogeneity both in allele and haplotype frequencies, unveiling a differential input of peoples from different origins. A PCA of the populations studied, plus other relevant ones, clearly shows gene heterogeneity in mainland Portugal as well as the differences and relationships between these populations and Madeira and Cabo Verde.