HLA class-I diversity in Cameroon: evidence for a north-south structure of genetic variation and relationships with African populations.

HLA class I diversity (loci A, B and C) was analysed in four populations, two from North Cameroon (Podokwo and Uldeme) and two from South Cameroon (Ewondo and Bamileke). Northern and southern Cameroon populations show a substantial genetic diversity in terms of haplotype sharing and genetic distances, even despite the low percentage of variance due to differences among populations evidenced by analysis of molecular variance. The signals of differentiation among populations are consistent with their linguistic affiliation, and support previous evidence, based on autosomal microsatellites and protein loci, which has shown that the complex pattern of genetic variation of Cameroon can in part be described by contrasting the northern and southern part of the country. Looking at our results in the more general framework of HLA diversity in sub-Saharan Africa, it turns out that the Podokwo and Uldeme show some genetic links to populations of the southern western branch of the Sahel corridor, while their high frequency of A*02 and C*04 alleles is congruent with previously hypothesised introgression of non-sub-Saharan alleles. On the other hand, signals of shared ancestry between the Bamileke and Ewondo and the Bantu speakers from central and southern Africa were detected.

Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal).

Hereditary HFE Hemochromatosis is an inherited disorder of iron metabolism that results from mutations in the HFE gene. Almost all patients with hereditary hemochromatosis show a C282Y mutation in homozygosity or in compound heterozygosity with H63D. Also, the mutation S65C has been shown to be associated to a milder iron overload. Since allele and genotype frequencies of these three variants of the HFE gene vary between populations, the determination of their prevalence in Madeira Island will clarify the population susceptibility to hereditary hemochromatosis. One hundred and fifty-four samples from Madeira Island were genotyped for the three most common HFE gene mutations, H63D, C282Y, and S65C, by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results have shown a prevalence of 20.5%, 0.33%, and 1% for H63D, C282Y, and S65C, respectively. Accordingly to our estimates, both genotypes associated to hereditary hemochromatosis, C282Y homozygotes and C282/H63D compound heterozygotes, could be present in Madeira Island population in 1,648 individuals, which represents 0.65% of the total population.

Evaluation of two methods for computational HLA haplotypes inference using a real dataset.

BACKGROUND: HLA haplotype analysis has been used in population genetics and in the investigation of disease-susceptibility locus, due to its high polymorphism. Several methods for inferring haplotype genotypic data have been proposed, but it is unclear how accurate each of the methods is or which method is superior. The accuracy of two of the leading methods of computational haplotype inference--Expectation-Maximization algorithm based (implemented in Arlequin V3.0) and Bayesian algorithm based (implemented in PHASE V2.1.1)--was compared using a set of 122 HLA haplotypes (A-B-Cw-DQB1-DRB1) determined through direct counting. The accuracy was measured with the Mean Squared Error (MSE), Similarity Index (IF) and Haplotype Identification Index (IH). RESULTS: None of the methods inferred all of the known haplotypes and some differences were observed in the accuracy of the two methods in terms of both haplotype determination and haplotype frequencies estimation. Working with haplotypes composed by low polymorphic sites, present in more than one individual, increased the confidence in the assignment of haplotypes and in the estimation of the haplotype frequencies generated by both programs. CONCLUSION: The PHASE v2.1.1 implemented method had the best overall performance both in haplotype construction and frequency calculation, although the differences between the two methods were insubstantial. To our knowledge this was the first work aiming to test statistical methods using real haplotypic data from the HLA region.

HLA genes in Madeira Island (Portugal) inferred from sequence-based typing: footprints from different origins.

Human leukocyte antigen (HLA)-A, HLA-B, and HLA-DRB1 polymorphisms were examined in Madeira Island populations. The data was obtained at high-resolution level, using sequence-based typing (SBT). The most frequent alleles at each loci were: A*020101 (24.6%), B*5101 (9.7%), B*440201 (9.2%), and DRB1*070101 (15.7%). The predominant three-loci haplotypes in Madeira were A*020101-B*510101-DRB1*130101 (2.7%) and A*010101-B*0801-DRB1*030101 (2.4%), previously found in north and central Portugal. The present study corroborates historical sources and other genetic studies that say Madeira were populated not only by Europeans, mostly Portuguese, but also sub-Saharan Africans due to slave trade. Comparison with other populations shows that Madeira experienced a stronger African influence due to slave trade than Portugal mainland and even the Azores archipelago. Despite this African genetic input, haplotype and allele frequencies were predominantly from European origin, mostly common to mainland Portugal.

HLA polymorphisms in Cabo Verde and Guiné-Bissau inferred from sequence-based typing.

Human leukocyte antigen (HLA)-A, -B, and -DRB1 polymorphisms were examined in the Cabo Verde and Guiné-Bissau populations. The data were obtained at high-resolution level, using sequence-based typing. The most frequent alleles in each locus was: A*020101 (16.7% in Guiné-Bissau and 13.5% in Cabo Verde), B*350101 (14.4% in Guiné-Bissau and 13.2% in Cabo Verde), DRB1*1304 (19.6% in Guiné-Bissau), and DRB1*1101 (10.1% in Cabo Verde). The predominant three loci haplotype in Guiné-Bissau was A*2301-B*1503-DRB1*1101 (4.6%) and in Cabo Verde was A*3002-B*350101-DRB1*1001 (2.8%), exclusive to northwestern islands (5.6%) and absent in Guiné-Bissau. The present study corroborates historic sources and other genetic studies that say Cabo Verde were populated not only by Africans but also by Europeans. Haplotypes and dendrogram analysis shows a Caucasian genetic influence in today's gene pool of Cabo Verdeans. Haplotypes and allele frequencies present a differential distribution between southeastern and northwestern Cabo Verde islands, which could be the result of different genetic influences, founder effect, or bottlenecks. Dendrograms and principal coordinates analysis show that Guineans are more similar to North Africans than other HLA-studied sub-Saharans, probably from ancient and recent genetic contacts with other peoples, namely East Africans.

Celiac disease in children from Madeira island and its prevalence in first degree relatives.

CONTEXT: It is well recognized that celiac disease is an immune-mediated systemic disorder highly prevalent among relatives of celiac patients. OBJECTIVES: The aim of this study is to determine the prevalence of celiac disease in a group of first degree relatives of celiac children, and to access the frequency of human leukocyte antigen HLA-DQ2 and DQ8 in celiac disease patients and their affected relatives. METHODS: A survey was conducted of 39 children with celiac disease with follow-up in the Pediatric outpatient's clinic of Dr. Nélio Mendonça Hospital, in Madeira Island, Portugal. Were invited 110 first degree relatives to undergo serological screen for celiac disease with IgA antibody to human recombinant tissue transglutaminase (IgA-TGG) quantification. In all seropositive relatives, small intestinal biopsy and HLA typing was recommended. RESULTS: HLA- typing was performed in 38 celiac patients, 28/74% DQ2 positive, 1/2% DQ8 positive and 9/24% incomplete DQ2. Positive IgA-TGG was found in five out of the 95 relatives, and CD was diagnosed in three of them. Three relatives had the presence of HLA-DQ2, two were DQ2 incomplete (DQB1*02). CONCLUSIONS: The prevalence of celiac disease among first degree celiac patients´ relatives was 3.1%, 4.5 times higher than the general Portuguese population (0,7%) witch reinforces the need of extensive diagnostic screening in this specific group. HLA-DQ2 typing may be a tool in the diagnostic approach.

Alpha-1-antitrypsin deficiency in the Cape Verde islands (Northwest Africa): High prevalence in a sub-Saharan population.

Alpha-1-antitrypsin (AAT) deficiency results from mutations on the Protease Inhibitor (PI) locus located in chromosome 14 and has been associated with pulmonary early-onset emphysema and chronic obstructive pulmonary disease (COPD). African populations show a lower prevalence of AAT deficiency compared to Europeans. Two hundred and two (202) unrelated samples from the Cape Verde archipelago (Northwest Africa) were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using PCR - Mediated Site-Directed Mutagenesis. PI*S mutation in Cape Verde (3.2%) presents one of the highest frequencies in sub-Saharans, similar to South Africa (3.3%) but lower than Angolans (18.8%), Namibians (14.7%), Nigerians (6.4%) and Botswains (4.5%). The PI*Z mutation shows lower values (0.2%) than other sub-Saharan populations, namely Somalia (1.15%), Mali (0.98%)or Nigeria (0.36%). However, many other sub-Saharan populations, like Botswana, Congo, Cameroon, Angola, Gambia, South Africa, Mozambique and Namibia, lack the PI*Z mutation. The frequency of all the AAT deficiency genotypes in the Cape Verde archipelago (PI*ZZ, PI*SS, and PI*SZ) was estimated to be one of the highest in sub-Saharans (15 per 1000), only lower than Angola (54 per 1000) and Namibia (22 per 1000). The results obtained show a high prevalence of the AAT deficiency in Cape Verdeans when compared to other sub-Saharans a condition that can be explained by a heavy European genetic influence, characteristic of that population.

Alpha-1-antitrypsin deficiency in Madeira (Portugal): the highest prevalence in the world.

Alpha-1-antitrypsin (AAT) deficiency is a common genetic disease which affects both lung and liver. Early diagnosis can help asymptomatic patients to adjust their lifestyle choices in order to reduce the risk of Chronic Obstructive Pulmonary Disease (COPD). The determination of this genetic deficiency prevalence in Madeira Island (Portugal) population is important to clarify susceptibility and define the relevance of performing genetic tests for AAT on individuals at risk for COPD. Two hundred samples of unrelated individuals from Madeira Island were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using Polymerase Chain Reaction-Mediated Site-Directed Mutagenesis. Our results show one of the highest frequencies for both mutations when compared to any already studied population in the world. In fact, PI*S mutation has the highest prevalence (18%), and PI*Z mutation (2.5%) was the third highest worldwide. The frequency of AAT deficiency genotypes in Madeira (PI*ZZ, PI*SS, and PI*SZ) is estimated to be the highest in the world: 41 per 1000. This high prevalence of AAT deficiency on Madeira Island reveals an increased genetic susceptibility to COPD and suggests a routine genetic testing for individuals at risk.

HLA polymorphism in six Malay subethnic groups in Malaysia.

In this study, human leukocyte antigen (HLA) class I and II were examined through sequence-specific primer typing in 176 unrelated individuals from six Malay subethnic groups of Peninsular Malaysia: Kelantan (n = 25), Minangkabau (34), Jawa (30), Bugis (31), Banjar (33), and Rawa (23). The most common HLA alleles in all groups were A*24 (26-41%), Cw*07 (24-32%), B*15 (22-30%), DRB1*12 (15-36%), and DQB1*03 (25-51%). The Malay subethnic groups studied demonstrated a close relationship to each other and to other Asian populations, despite specific differences between them. Banjar, Bugis, and Jawa Malays demonstrated no significant difference from each other, which could be a result of their related origin from the islands around the Java Sea. These three Malay subethnic groups were then collapsed into one group, which also helped to increase the sample number and sharpen statistical results. Minangkabau and Rawa Malays exhibited high similarities in allele group and haplotype frequencies, which could be a consequence of their common origin from Sumatera. Kelantan Malays, in addition to their statistically significant differences compared with the other groups, also exhibited differences on the most frequent haplotypes, which are almost absent in the other subethnic groups studied.

Celiac disease nn children from madeira island and its prevalence in first degree reaatives / Doença celíaca em idade pediátrica na Ilha da Madeira e sua prevalência em familiares de primeiro grau

Context It is well recognized that celiac disease is an immune-mediated systemic disorder highly prevalent among relatives of celiac patients. Objectives The aim of this study is to determine the prevalence of celiac disease in a group of first degree relatives of celiac children, and to access the frequency of human leukocyte antigen HLA-DQ2 and DQ8 in celiac disease patients and their affected relatives. Methods A survey was conducted of 39 children with celiac disease with follow-up in the Pediatric outpatient’s clinic of Dr. Nélio Mendonça Hospital, in Madeira Island, Portugal. Were invited 110 first degree relatives to undergo serological screen for celiac disease with IgA antibody to human recombinant tissue transglutaminase (IgA-TGG) quantification. In all seropositive relatives, small intestinal biopsy and HLA typing was recommended. Results HLA- typing was performed in 38 celiac patients, 28/74% DQ2 positive, 1/2% DQ8 positive and 9/24% incomplete DQ2. Positive IgA-TGG was found in five out of the 95 relatives, and CD was diagnosed in three of them. Three relatives had the presence of HLA-DQ2, two were DQ2 incomplete (DQB1*02). Conclusions The prevalence of celiac disease among first degree celiac patients´ relatives was 3.1%, 4.5 times higher than the general Portuguese population (0,7%) witch reinforces the need of extensive diagnostic screening in this specific group. HLA-DQ2 typing may be a tool in the diagnostic approach. .

Contexto A doença celíaca é uma doença sistémica autoimune muito prevalente nos familiares de primeiro grau de doentes celíacos. Objetivos O objetivo deste estudo é determinar a prevalência de doença celíaca, num grupo de familiares de primeiro grau de crianças com o diagnóstico de doença celíaca e, determinar a frequência de antígeno leucocitário humano (HLA)-DQ2 e DQ8 nos doentes celíacos e seus familiares afetados. Métodos Foi feita a pesquisa dos processos clínicos de 39 crianças com o diagnóstico de doença celíaca seguidas na consulta de Gastroenterologia Pediátrica do Hospital Dr. Nélio Mendonça na Ilha da Madeira, Portugal. Foram convidados 110 familiares de primeiro grau para a realização do rastreio serológico de doença celíaca através da quantificação do anticorpo IgA anti-transglutaminase tecidular humano (IgA-TGG). Aos familiares com resultado positivo no rastreio, foi recomendada a realização de biópsia intestinal e tipificação HLA. Resultados A tipificação HLA foi realizada em 38 crianças. Verificou-se a presença do heterodímero DQ2 em 28/74%, DQ8 em 1/2% e DQ2 incompleto em 9/24% das crianças. O rastreio de DC com IgA-TGG foi positivo em cinco dos 95 familiares analisados, tendo sido diagnosticada doença celíaca em três destes. Verificou-se a presença do heterodímero HLA-DQ2 em três familiares e HLA-DQ2 incompleto (DQB1*02) em dois familiares. Conclusões A prevalência de doença celíaca em familiares de primeiro grau de doentes celíacos foi 3.1%, 4.5 vezes mais elevada do que a da população Portuguesa geral (0,7%), o que reforça a importância de alargar o rastreio a este grupo específico. A tipificação ...

Discrepancies in HLA typing by PCR-SSOP and SBT techniques: a case study.

Six hundred twenty-one samples from Portugal, the Cabo Verde archipelago, and Guinea-Bissau were typed for HLA-A, HLA-B, and HLA-DRB1 using the polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) method and the sequence-based typing (SBT) method to characterize and compare discrepancies between the two methods. Fifty-three alleles (4.27% of 1242 chromosomes typed) identified by the PCR-SSOP method were not concordant with the results obtained using the SBT method. Thirty-four (2.74% of total chromosomes typed) PCR-SSOP mistyping results were discrepancies inside the same allele group and 19 others (1.53% of total chromosomes typed) were relative to nonconcordant results between different groups. PCR-SSOP allele mistyping is the result of interpretation difficulties resulting from less intense, absent, or dubious hybridization patterns. Noncommercial PCR-SSOP procedures are highly exigent on the technicians' experience and the availability of properly calibrated high-precision equipment.

Y-chromosome lineages in São Tomé e Príncipe islands: evidence of European influence.

The Y-chromosome haplogroup composition of the population of São Tomé e Príncipe (STP) archipelago was analyzed using 25 biallelic markers and compared with populations of different origins from Europe, Africa, and the Middle East. Two main Y-chromosome haplogroups were found: E3a, very common among sub-Saharans accounts for 84.2% of the paternal lineages and R1b, typical of West Eurasia, represents 8.7% of the overall male population. Nevertheless, we detected in the population of STP a significant heterogeneous distribution of R1b among the two main ethnic groups of the archipelago: Forros (10.3%) and Angolares (6.6%). Together, haplogroups known to be prevalent in West Eurasia reach 12.5% of the chromosomes analyzed unequally distributed among the two groups: Forros present 17.7% while Angolares display only 8.2% of west Eurasian haplogroups. Our findings suggest that, despite its sub-Saharan genetic background, a relevant contribution of European paternal lineages is present in nowadays STP population. This influence has shown to be stronger in Forros than in Angolares, which could be explained by the social isolation that these have last experienced through their history.