Sedeka Abd-El-Fatah-Khalil

HLA genes in Uros from Titikaka Lake, Peru: origin and relationship with other Amerindians and worldwide populations

Uros population from the Titikaka Lake live in about 42 floating reed (‘totora’) islands in front of Puno City (Peru) at a 4000 m high altiplano. They present both an mtDNA and a human leucocyte antigen (HLA) profile different from the surrounding populations: mtDNA A2 haplogroup is common to Uros and Amazon forest lowland Amerindians. HLA genetic distances between populations have been calculated and neighbour‐joining dendrograms and correspondence analyses were carried out. Approximately 15 006 HLA chromosomes from worldwide populations have been used for comparisons. Only eight HLA‐A alleles have been found, three of them accounting for most of the frequencies. The same phenomenon is seen for HLA‐B, HLA‐DRB1 and HLA‐DQB1 alleles: a few alleles (3, 4 and 3, respectively) are present in most individuals. The presence of HLA‐B*4801 and HLA‐DRB1*0901 alleles in a relatively high frequency (although not the most frequent alleles found) is a characteristic shared with Asians and some populations from the Andean altiplano. Three specific Uros haplotypes have been found among the most frequent ones: HLA‐A*680102‐B*3505‐DRB1*0403‐DQB1*0302; HLA‐A*2402‐B*1504‐DRB1*1402‐DQB1*0301; and HLA‐A*2402‐B*4801‐DRB1*0403‐DQB1*0302. The present study suggests that Uros may have been one of the first populations from the shores of the Titikaka Lake coming from the Amazonian forest, which might have given rise to other later differentiated ethnic group (i.e. Aymaras). Uros HLA profile is also useful to study genetic epidemiology of diseases linked to HLA and to construct a future transplant waiting list by adding up regional lists in order to get a bigger pool for transplanting with better HLA matching.

HLA Genes in Afro-American Colombians (San Basilio de Palenque): The First Free Africans in America

An Afro-American semi-isolated Colombian population is studied for its HLA genes: San Basilio de Palenque community in Colombia northern mountains. This community represents the first free Africans in America earning recog- nition by the Spanish Crown in 1691 AD. Nowadays, they also speak the only extant Bantu-Spanish Creole language over the World; these people have been apart from there neighbours and claim a direct African descent. Their HLA genes were compared with African, Afro-American, Amerindian and worldwide populations by using genetic distances (DA), Neigh- bour-Joining dendograms and correspondences analyses. Arlequin, DISPAN and VISTA softwares were used for the completion of these computerised calculations. San Basilio de Palenque, a relatively ethnic isolate, is genetically close to other North and South Afro-Americans and to West Africa-Bantu speaking groups (Senegalese; Bubi, Guinea Gulf). Five HLA extended haplotypes are found only in this population: A*02-B*07-DRB1*0801-DQB1*0301, A*02-B*35- DRB1*1304-DQB1*0301, A*02-B*15-DRB1*0302-DQB1*0402, A*01-B*51-DRB1*0301-DQB1*0201, A*68-B*15- DRB1*0102-DQB1*0501. Only very limited gene flow is found from either Amerindians or Europeans, as expected by historical records. Our HLA data may also prove useful for future regional transplant programs and genetic epidemiology of HLA-linked diseases.

Amerindians show association to obesity with adiponectin gene SNP45 and SNP276: population genetics of a food intake control and “thrifty” gene

Adiponectin gene polymorphisms SNP45 and SNP276 have been related to metabolic syndrome (MS) and related pathologies, including obesity. However results of associations are contradictory depending on which population is studied. In the present study, these adiponectin SNPs are for the first time studied in Amerindians. Allele frequencies are obtained and comparison with obesity and other MS related parameters are performed. Amerindians were also defined by characteristic HLA genes. Our main results are: (1) SNP276 T is associated to low diastolic blood pressure in Amerindians, (2) SNP45 G allele is correlated with obesity in female but not in male Amerindians, (3) SNP45/SNP276 T/G haplotype in total obese/non-obese subjects tends to show a linkage with non-obese Amerindians, (4) SNP45/SNP276 T/T haplotype is linked to obese Amerindian males. Also, a world population study is carried out finding that SNP45 T and SNP276 T alleles are the most frequent in African Blacks and are found significantly in lower frequencies in Europeans and Asians. This together with the fact that there is a linkage of this haplotype to obese Amerindian males suggest that evolutionary forces related to famine (or population density in relation with available food) may have shaped world population adiponectin polymorphism frequencies.

The peopling of Madeira archipelago (Portugal) according to HLA genes

The Madeira‐Porto Santo Archipelago was officially colonized in 1420 by Portuguese settlers. Its importance in Columbus’ information for the American discovery and for slave traffic across the Atlantic is unquestionable. Thus, a complex peopling may have given rise to a present‐day high admixture of ethnicities according to HLA genes. A sample of 173 healthy unrelated Madeirans was analysed and compared with 6986 HLA chromosomes from other worldwide populations. Genetic distances, neighbour‐joining dendrograms and correspondence analyses were used for comparisons. Southern European, North African (including Canary Islands), Jewish and Mediterranean typical HLA alleles were found and genetic distances from Madeirans to these populations were the closest ones. In addition A*24‐B*65‐DRB1*0102‐DQB1*0501 and A*68‐B*08‐DRB1*0301‐DQB1*0201 haplotypes were newly found in Madeira and not found in any other population. Jewish‐Armenian‐Middle East haplotype (A*33‐B*65‐DRB1*0102‐DQB1*0501) is one of the most common haplotypes; this haplotype is also present in Spaniards and North Africans. Quantitatively, Portuguese, North Africans (Algerians), Spaniards and Canary Islanders (in this order) are the most important parental populations to Madeirans. Results are discussed on the basis of the recorded historical peopling which does not show a noticeable African gene input in present‐day Madeiran population according to our data; one of the closest related populations found is the Canary Islanders, suggesting that Guanche (Canary Islands first inhabitants) slaves gene flow is still noticed at present, both in Madeira and in Canary Islands populations.

Mixtec Mexican Amerindians: an HLA alleles study for America peopling, pharmacogenomics and transplantation.

HLA-A, -B and -DRB1 alleles have been studied in a Mixtec Mexican Amerindian population by indirect DNA sequencing. HLA relatedness has been tested by comparing results with other Amerindians and worldwide populations; a total of 15,681 chromosomes have been used. Genetic distances between populations, Neighbour Joining (NJ) dendrograms and correspondence analyses have been carried out. Conclusions are: 1) Our Mixtec sample from Oaxaca Coastal Mexican area shows an HLA profile different to that of Oaxaca Central Mountains area showing that genes and languages do not correlate which is inferred both by plane genetic distances and NJ dendrograms and correspondence analyses. 2) Genetic distances and NJ dendrograms join together Mazatecan Mexican Amerindians with our studied Coastal Mixtec group; it fits with the historical relationship between Mixtec and Mazatecans. 3) A*24:02-B*35:14-DRB1*04:11, A*02:01-B*15:15-DRB1*04:11 and A*68:03-B*39:08-DRB1*08:02 extended HLA haplotypes have been “de novo” found in our Mixtec Coastal sample. 4) Shared HLA alleles are found between our Pacific Coast Mixtec Amerindians and Pacific Islanders. 5) These results are useful for establishing a future area transplantation waiting list, for the study of HLA linked diseases epidemiology and for pharmacogenomics in certain drug therapy.

Gorgan (Turkmen in Iran) HLA genetics: transplantation, pharmacogenomics and anthropology

HLA class I and II alleles have been studied in a population from Gorgan (North East Iranian city bordering Turkmenistan). This population is composed of mainly Turkmen who speak Oghuz Turkish language. Comparison of Gorgan people HLA profile has been carried out with about 7984 HLA chromosomes from other worldwide populations; extended haplotypes and three dimension genetic distances have been calculated by using neighbor-joining and correspondence relatedness analyses. Most frequent extended HLA haplotypes show a Siberian/Mediterranean admixture and closest populations are Chuvashians (North Caspian Sea, Russia) and other geographically close populations like Siberian Mansi, Buryats and other Iranians. New extended HLA haplotypes have been found, such as: A*31:01-B*35:01-DRB1*15:01-DQB1*03:01, A*01:01-B*35:01-DRB1*03:01-DQB1*02:01. Relationships of Turkmen with Kurgan (Gorgan) archaeological mounds, Scythians and Sarmatians are discussed. This study is also useful for a future transplantation Gorgan waiting list, Gorgan HLA and disease epidemiology and HLA pharmacogenomics.

Amerindians show no association of PPAR-γ2 gene Ala12 allele and obesity: an “unthrifty” variant population genetics

Obesity is for many scholars the most important starting status that gives rise to Metabolic Syndrome (MS) and Type 2 Diabetes (T2D). In the present paper, a genetically homogeneous Amerindian population, as defined by HLA genes, has been genotyped for one of the MS and T2D predisposing genes: PPAR-γ Ala12 and Pro 12 variants. Ala12 has been negatively associated with obesity, but other authors do not find such an association. Notwithstanding, a meta-analysis that used many subjects clearly demonstrated that PPAR-γ Ala12 bearing ones had a reduced risk for T2D. Our results show that Amerindians do not have association of PPAR-γ2 Ala12 and obesity; the latter was measured by waist circumference values after taken specific Amerindian normal waist parameters. Also, a population genetics study indicates that Pro12 allele was the wild allele, which must have occurred before modern humans left Africa. Ala12 may have appeared in Caucasoids later on, according to our comparisons. Negroids tend to show low or null Ala 12 allele frequencies, while most other populations have a significant frequency, particularly European Caucasoids. This may suggest that appearance of Ala12 allele occurred after populations adapted to an agricultural feeding.

HLA in Georgians (Caucasus) and their relationship with Eastern Mediterraneans.

AbstractHLA-A, -B, -DQB1, and –DRB1 typing has been performed in a sample of Georgian population (South Caucasus). Allele frequencies, neighbour joining and correspondence relatedness analyses and extended HLA haplotypes have been obtained with comparison with other Middle East and Mediterranean populations. Our Georgian sample tends to be genetically related in these analyses with Eastern Mediterraneans and Middle East people. This is important for future regional transplant programs, and Georgian HLA and disease epidemiology and pharmacogenomics.