Amerindians normalized waist circumference and obesity diagnosis standarized by biochemical and HLA data

Metabolic syndrome (MS) and obesity are principal causes of morbidity all over the World, particularly for their association to cardiovascular risk. Amerindians are often living in countries and remote areas with unavailable sophisticated diagnoses methodologies. However, waist-circumference is a reliable and easy to record parameter of visceral obesity and MS. Waist circumference normal values are not yet established in Amerindians: South Asian and Japanese values have been recommended for Amerindian use. The purpose of this study is to objectively define for the first time the waist circumference measure cut-off points for Amerindians. A total of 303 unrelated Amerindian adults recently immigrated to Madrid were studied; they were healthy, since they were questioned and tested as appropriate for blood donation. Waist-circumference was measured in these voluntary blood donors after written consent. Chosen subjects for study had HLA quasi-specific Amerindian genes and not gained weight since their relatively short time living in Spain. Amerindians with Type I or II diabetes or family antecedents were removed from the study. The biochemical parameter used to define normality for MS was the reliable serum HDL-cholesterol levels, whose values are diet independent. A Receiver Operating Characteristic analysis was used to compare the predictive validity and to find out the optimal cut-off points of waist circumference normal values. Cut-off points were ≤88.5 cm in males and ≤82.5 cm in females; these values were close to the median values (88 and 82.2 cm, respectively). Obtained waist circumference values recorded here in normal Amerindians are different to those previously recommended indirectly (those of South Asian/Japanese populations). These parameters may be of great value for American countries health care in order to predict and control MS and its cardiovascular complications. Other countries having a heavy Amerindian immigration (i.e.: USA, Spain) may also benefit for establishing specific Preventive Medicine programs.     

HLA genetic profile of Mapuche (Araucanian) Amerindians from Chile

Amerindian Mapuche (Araucanians) are now living in Chile and Argentina at both sides of Andean Mountains. They are anthropologically and genetically different from southernmost South America Patagonian Amerindians. Most of the HLA alleles found in our Mapuche sample are frequent or very frequent in North and South America Amerindians: (1) Class I: A*02:01, A*03:01, A*68:01, B*39:09, B*51:01, (2) Class II: DRB1*03:01, DRB1*04:03, DRB1*07:01, DRB1*08:02, DRB1*14:02, DRB1*16:02. One of the nine most frequent extended haplotypes seems to be from European origin, suggesting the existence of a degree of admixture with Europeans in our Mapuche sample. It has been calculated of about 11 % admixture. Three of the extended haplotypes are also found in other Amerindians and five of them are newly found in Mapuche Amerindians: A*68:01-B*39:09-DRB1*08:02-DQB1*04:02; A*68:01-B*51:01-DRB1*04:03-DQB1*03:02; A*29:01-B*08:01-DRB1*03:01-DQB1*02:01; A*02:01-B*15:01-DRB1*04:03-DQB1*03:02; A*33:01-B*14:02-DRB1*07:01-DQB1*03:03. The medical importance of calculating HLA profile is discussed on the diagnostic (HLA and disease) and therapeutical bases of HLA pharmacogenomics and on the construction of a virtual transplantation HLA list profile. Also, anthropological conclusions are drawn.     

HLA in Jaidukama: an Amerindian secluded Colombian population with new haplotypes and Asian and Pacific-shared alleles

America first inhabitants and peopling are still debated. In order to increase knowledge about these questions, we have aimed to detect HLA genes of an Amerindian secluded community: Jaidukama, who lives in North Colombia Equatorial forest. HLA genotyping and extended haplotype calculations were carried out in 39 healthy individuals belonging to 13 families. HLA frequencies were compared to other Amerindians and worldwide populations by calculating genetic distances, relatedness dendrograms and correspondence analyses. Only four DRB1 alleles were found (*0404, *0407, *1402 and *1602); however a total of 17 Amerindian different extended class I–class II HLA haplotypes were directly counted from the family studies, nine of them were specific of Jaidukamas. Some of the alleles or group of alleles within an extended haplotype (i.e. DQB1–DRB1) were also found in Asians and Pacific Islanders, further supporting existence of Asian and Pacific gene flow with Amerindians or a common founder effect. It is further supported that HLA extended haplotypes vary faster than alleles in populations. It is concluded that this unique model of Amerindian secluded families study suggests that rapid HLA haplotype variation may be more important than allele variation for survival (starting immune responses). This work may also be useful for future transplant programs in the area.     

Genetic diversity in an Andean population from Peru and regional migration patterns of Amerindians in South America: data from Y chromosome and mitochondrial DNA

The genetic variability of a Quechua-speaking Andean population from Peru was examined on the basis of four Y chromosome markers and restriction sites that define the Amerindian mitochondrial DNA (mtDNA) haplogroups. Forty-nine out of 52 (90.4%) individuals had mtDNA which belonged to one of the four common Amerindian haplogroups, with 54% of the samples belonging to haplogroup B. Among 25 males, 12 had an Amerindian Y chromosome, which exists as four haplotypes defined on the basis of the DYS287, DYS199, DYS392 and DYS19 markers, three of which are shared by Amazonian Amerindians. Thus, there is a clear directionality of marriages, with an estimated genetic admixture with non-Amerindians that is 9 times lower for mtDNA than for Y chromosome DNA. The comparison of mtDNA of Andean Amerindians with that of people from other regions of South America in a total of 1,086 individuals demonstrates a geographical pattern, with a decreasing frequency of A and C haplotypes and increasing frequency of the D haplotype from the north of the Amazon River to the south of the Amazon River, reaching the lowest and the highest frequencies, respectively, in the more southern populations of Chile and Argentina. Conversely, the highest and lowest frequencies of the haplogroup B are found, respectively, in the Andean and the North Amazon regions, and it is absent from some southern populations, suggesting that haplotypes A, C and D, and haplotype B may have been dispersed by two different migratory routes within the continent.     

Human T cell lymphotropic viruses (HTLV-I/II) in South America: Should it be a public health concern?

The presence of the human T cell lymphotropic virus (HTLV-I/II) in South America is well established. Its origin and spectrum in the continent still remain a matter of debate. There are signs now that HTLV-I/II was already present in the Amerindian population coming originally from Asia and that HTLV-I was also introduced with African slave trade and with immigration of individuals from endemic areas of Japan. South America has approximately 350 million inhabitants in its 13 countries. The presence of HTLV-I/II has been reported with impressive numbers in most of them and may be considered endemic in this continent. The distribution of HTLV I/II among native Amerindian populations has shown a geographic clustering of type I in the Andean highlands and Brazilian coast, while type II predominates in lowlands of South America. Although comparability between studies conducted among blood donors in different countries may be difficult, the data indicate that the viruses are also circulating among otherwise healthy individuals. Undoubtedly, HTLV-I/II infection and its related diseases should be considered a public health concern in South America and measures to prevent its spread should be emphasized.     

Genetic variation in Arizona Mexican Americans: estimation and interpretation of admixture proportions

Mexican Americans are a numerous and fast growing ethnic population in the United States. Yet little is known about their genetic structure. Since they are a hybrid, it is of interest to identify their parental populations and to estimate the relative contributions of these groups. This information is relevant to historical, biomedical, and evolutionary concerns. New genetic typings on 730 Arizona Mexican Americans for the HLA-A, HLA-B, ABO, Rh, MNSs, Duffy, Kidd, and Kell loci are presented here and they are used to estimate ancestral contributions. We considered both a dihybrid model with Amerindians and Spaniards as proposed ancestors, and a trihybrid model with Amerindians, Spaniards, and Africans as proposed ancestors. A modified weighted least squares method that allows for linkage disequilibrium was used to estimate ancestral contributions for each model. The following admixture estimates were obtained: Amerindian, 0.29 +/- 0.04; Spaniard, 0.68 +/- 0.05; and African, 0.03 +/- 0.02. The interpretation of these results with respect to Amerindian and Spanish ancestry is straightforward. African ancestry is strongly supported by the presence of a marker of African descent, Fy, despite the fact that the standard error of the estimate is as large as the estimated admixture proportion. An evaluation of the sensitivity of these results to a number of variables is presented: 1) our choices of ancestral allele frequencies, 2) the possibility of selection at HLA and the blood groups, and 3) genetic drift in Mexican Americans.     

Founder mitochondrial haplotypes in Amerindian populations.

It had been proposed that the colonization of the New World took place by three successive migrations from northeastern Asia. The first one gave rise to Amerindians (Paleo-Indians), the second and third ones to Nadene and Aleut-Eskimo, respectively. Variation in mtDNA has been used to infer the demographic structure of the Amerindian ancestors. The study of RFLP all along the mtDNA and the analysis of nucleotide substitutions in the D-loop region of the mitochondrial genome apparently indicate that most or all full-blooded Amerindians cluster in one of four different mitochondrial haplotypes that are considered to represent the founder maternal lineages of Paleo-Indians. We have studied the mtDNA diversity in 109 Amerindians belonging to 3 different tribes, and we have reanalyzed the published data on 482 individuals from 18 other tribes. Our study confirms the existence of four major Amerindian haplotypes. However, we also found evidence supporting the existence of several other potential founder haplotypes or haplotype subsets in addition to the four ancestral lineages reported. Confirmation of a relatively high number of founder haplotypes would indicate that early migration into America was not accompanied by a severe genetic bottleneck.     

HLA genes in populations of the Aleutian islands

We typed a subset of the Aleut population for HLA loci (HLA-A, HLA-B, HLA-DRB1, HLA-DQB1) to obtain an HLA profile, which was compared to other Eurasian and Amerindian populations for studying Aleut origin and its significance on the peopling of the Americas. Allele frequencies at the four loci were identified in an Aleut sample using standard indirect DNA sequencing methods. Genetic distances with Amerindians and Eurasians were obtained by comparing Aleut allele frequencies with a worldwide population database (13,164 chromosomes). The most frequently extended HLA haplotypes were also calculated. We also generated Aleut relatedness dendrograms and calculated correspondence relatedness in a multidimensional scale. Both neighbor-joining dendrograms and correspondence analysis separated Aleuts from Eskimos and Amerindians. Aleuts are closer genetically to Europeans, including Scandinavians and English. Our results are concordant with those obtained by Y-chromosome analysis, suggesting that most male Aleut ancestors of our sample came mainly from Europe.     

Genetic differentiation in South Amerindians is related to environmental and cultural diversity: evidence from the Y chromosome

The geographic structure of Y-chromosome variability has been analyzed in native populations of South America, through use of the high-frequency Native American haplogroup defined by the DYS199-T allele and six Y-chromosome-linked microsatellites (DYS19, DYS389A, DYS389B, DYS390, DYS391, and DYS393), analyzed in 236 individuals. The following pattern of within- and among-population variability emerges from the analysis of microsatellite data: (1) the Andean populations exhibit significantly higher levels of within-population variability than do the eastern populations of South America; (2) the spatial-autocorrelation analysis suggests a significant geographic structure of Y-chromosome genetic variability in South America, although a typical evolutionary pattern could not be categorically identified; and (3) genetic-distance analyses and the analysis of molecular variance suggest greater homogeneity between Andean populations than between non-Andean ones. On the basis of these results, we propose a model for the evolution of the male lineages of South Amerindians that involves differential patterns of genetic drift and gene flow. In the western part of the continent, which is associated with the Andean area, populations have relatively large effective sizes and gene-flow levels among them, which has created a trend toward homogenization of the gene pool. On the other hand, eastern populations-settled in the Amazonian region, the central Brazilian plateau, and the Chaco region-have exhibited higher rates of genetic drift and lower levels of gene flow, with a resulting trend toward genetic differentiation. This model is consistent with the linguistic and cultural diversity of South Amerindians, the environmental heterogeneity of the continent, and the available paleoecological data.     

The population genetics of Quechuas, the largest native South American group: autosomal sequences, SNPs, and microsatellites evidence high level of diversity

Elucidating the pattern of genetic diversity for non-European populations is necessary to make the benefits of human genetics research available to individuals from these groups. In the era of large human genomic initiatives, Native American populations have been neglected, in particular, the Quechua, the largest South Amerindian group settled along the Andes. We characterized the genetic diversity of a Quechua population in a global setting, using autosomal noncoding sequences (nine unlinked loci for a total of 16 kb), 351 unlinked SNPs and 678 microsatellites and tested predictions of the model of the evolution of Native Americans proposed by (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485-1496). European admixture is <5% and African ancestry is barely detectable in the studied population. The largest genetic distances were between African versus Quechua or Melanesian populations, which is concordant with the African origin of modern humans and the fact that South America was the last part of the world to be peopled. The diversity in the Quechua population is comparable with that of Eurasian populations, and the allele frequency spectrum based on resequencing data does not reflect a reduction in the proportion of rare alleles. Thus, the Quechua population is a large reservoir of common and rare genetic variants of South Amerindians. These results are consistent with and complement our evolutionary model of South Amerindians (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485-1496), proposed based on Y-chromosome data, which predicts high genomic diversity due to the high level of gene flow between Andean populations and their long-term effective population size.     

Maturational profiles and migration in the female adolescent population of Madrid: is there a need for a new perspective?

The aim of this study is to assess anthropometric changes and menstrual cycle characteristics during the maturation process of an adolescent female sample in Madrid, Spain. The new demographic context of Madrid, with a 33.9% of girls coming from Central and South America, makes this study relevant in terms of new epidemiological situations that could possible develop. The sample consists of 284 girls, ages 9 to 16 years, measured and interviewed in four school centres of Madrid. Results show that menarche is slightly earlier in the Spanish girls, but there are no other important differences regarding the characteristics of their menses. However, the Spanish girls have a significantly higher intake of menarcheal pain related drugs. The anthropometric changes accompanying menarche are greater in the immigrants, especially in terms of trunk fatness, leading to an "overweight" characterisation of this sub-sample. These maturational profiles show the need for educational programs, especially focussed on the foreign adolescent population, to cope with health risks related to overweight.     

A "disproportion" between the frequency of rare electropmorphs and enzyme deficiency variants in Amerindians

Our previous studies have revealed a higher frequency of nonpolymorphic electrophoretic variants in blood samples from Amerindians than in similar samples from Caucasians and Japanese. Our present study finds, by contrast, that the frequency of deficiency variants of 11 erythrocyte enzymes, sampled in nine Amerindian tribes of Central and South America, is essentially the same (1.5/1,000 determinations) as in Caucasians or Japanese. Possible explanations of the elevated frequency of mobility variants in the tropical-zone/ unacculturated populations include: higher mutation rates resulting in both electrophoretic and activity variants in Amerindians but increased selection against deficiency variants in the Amerindians, or comparable mutation rates in both populations coupled with a greater probability of a mobility variant attaining a relatively high frequency among the Amerindians.     

South Amerindian craniofacial morphology: diversity and implications for Amerindian evolution

The most compelling models concerning the peopling of the Americas consider that modern Amerindians share a common biological pattern, showing affinities with populations of the Asian Northeast. The aim of the present study was to assess the degree of variation of craniofacial morphology of South American Amerindians in a worldwide context. Forty-three linear variables were analyzed on crania derived from American, Asian, Australo-Melanesian, European, South-Saharan African, and Polynesian regions. South America was represented by seven Amerindian samples. In order to understand morphologic diversity among Amerindians of South America, variation was estimated using regions and local populations as units of analysis. Variances and F(ST) values were calculated for each unit, respectively. Both analyses indicated that morphologic variation in Southern Amerindians is extremely high: an F(ST) of 0.01531 was obtained for Southern Amerindians, and values from 0.0371-0.1205 for other world regions. Some aspects linked to the time and mode of the peopling of the Americas and various microevolutionary processes undergone by Amerindians are discussed. Some of the alternatives proposed to explain this high variation include: a greater antiquity of the peopling than what is mostly accepted, a peopling by several highly differentiated waves, an important effect of genetic drift, and gene flow with Paleoamericans. A combination of some of these alternatives explains at least some of the variation.     

Las Alpujarras region (South East Spain) HLA genes study: evidence of a probable success of 17th century repopulation from North Spain

Conquest of Granada Muslim Kingdom (1492 AD) finished with Muslim occupation; they were mostly North African Berbers who had reached Iberia by 711 AD. A politics of Iberian Christianization followed after this date: Jewish were expelled in 1492 and Moriscos (Spaniards practicing Muslim religion or speaking Arab) were expelled from all Spanish territory on 1609 AD. Las Alpujarras is a southern Spain mountainous secluded region, which underwent a repopulation from North Spain and a specific Muslim (Moriscos)–Christian war took place according to historical records. Both Las Alpujarras repopulation by northern Iberians and Moriscos expulsion success have been debated and are regarded as non-clarified episodes. In this study, we have addressed the question whether the repopulation succeeded by determining HLA genes of present day Las Alpujarras inhabitants and compared with those of other Mediterranean populations HLA frequencies and genealogies. HLA frequencies show ambiguous results because of extant HLA similar gene frequencies there exist in North Africa and Spain. This is reflected by the finding of North and South western Mediterraneans close relatedness of HLA dendrograms and correspondence analyses. However, the genealogical study of extended HLA haplotypes particularly Alpujarran high frequency of HLA-A29-B44-DRB1*0701-DQA1*02-DQB1*02 (not found in Algerians but frequent in North and Central Spain) and Alpujarran low frequency extended haplotype HLA-A3-B7-DRB1*1501-DQA1*0102-DQB1*0602 (frequent in North Europe) reveals that a significant HLA gene flow from North Spain is observed in present day Alpujarrans: both haplotypes are characteristic of North Spain and North Europe, respectively. This may indicate that enforced Alpujarran repopulation from North Spain may have been a success, which was started by Spanish King Philip II in 1571 AD.     

Possible migration routes into South America deduced from mitochondrial DNA studies in Colombian Amerindian populations

Mitochondrial DNA haplotype studies have been useful in unraveling the origins of Native Americans. Such studies are based on restriction site and intergenic deletion/insertion polymorphisms, which define four main haplotype groups common to Asian and American populations. Several studies have characterized these lineages in North, Central, and South American Amerindian, as well as Na Dene and Aleutian populations. Siberian, Central Asian, and Southeast Asian populations have also been analyzed, in the hope of fully depicting the route(s) of migration between Asia and America. Colombia, a key route of migration between North and South America, has until now not been studied. To resolve the current lack of information about Colombian Amerindian populations, we have investigated the presence of the founder haplogroups in 25 different ethnic groups from all over the country. The present research is part of an interdisciplinary program, Expedición Humana, fostered by the Universidad Javeriana and Dr. J. E. Bernal V. The results show the presence of the four founder A-D Amerindian lineages, with varied distributions in the different populations, as well as the presence of other haplotypes in frequencies ranging from 3% to 26%. These include some unique or private polymorphisms, and also indicate the probable presence of other Asian and a few non-Amerindian lineages. A spatial structure is apparent for haplogroups A and D, and to a lesser extent for haplogroup C. While haplogroup A and D frequencies in Colombian populations from the northwestern side of the Andes resemble those seen in Central American Amerindians more than those seen in South American populations, their frequencies on the southeastern side more closely resemble the bulk of South American frequencies so far reported, raising the question as to whether they reflect more than one migration route into South America. High frequencies of the B lineage are also characteristic of some populations. Our observations may be explained by historical events during the pre-Columbian dispersion of the first settlers and, later, by disruptions caused by the European colonization.     

Cytochrome P4501A1 polymorphisms in the Amerindian and Mestizo populations of Mexico

Several polymorphisms in the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. We studied two CYP1A1 polymorphic sites (position 4889 and 6235) in a group of 212 unrelated healthy individuals belonging to three different Mexican populations (106 Mexican Mestizos, 52 Teenek and 54 Mayos). Comparison among Mexican populations showed increased frequency of the *Ile allele (A on position 4889) in Mexican Mestizos when compared to Amerindians (p < 0.05). The analysis of position 6235 showed increased frequencies of *m2 (C in this position) allele in Teenek when compared to Mestizos and Mayos (p < 0.05) and of *m2/*m2 genotype when compared to Mestizos (p < 0.05). Amerindian populations (from Mexico and South America) presented the lowest frequencies of *Ile (position 4889) and *m1 (position 6235) alleles, however these frequencies vary according to the ethnic group studied. Mexican Amerindian groups together with other South Amerindian populations showed the highest frequencies for *Val at position 4889 and the *m2 allele at position 6235. The present study corroborates the high frequencies of*Val and *m2 alleles in the Amerindian populations and detects some differences between Mexican populations that correlate with linguistic differences. Our data could be helpful in understanding the distribution of these polymorphisms and in clarifying their roles as genetic and evolution markers in Amerindian populations.     

The Origin of Amerindians and the Peopling of the Americas According to HLA Genes: Admixture with Asian and Pacific People

The classical three-waves theory of American peopling through Beringia was based on a mixed anthropological and linguistic methodology. The use of mtDNA, Y chromosome and other DNA markers offers different results according to the different markers and methodologies chosen by different authors. At present, the peopling of Americas remains uncertain, regarding: time of population, number of peopling waves and place of peopling entrance among other related issues. In the present review, we have gathered most available HLA data already obtained about First Native American populations, which raise some doubts about the classical three waves of American peopling hypothesis. In summary, our conclusions are: 1) North West Canadian Athabaskans have had gene flow with: a) close neighboring populations, b) Amerindians, c) Pacific Islanders including East Australians and d) Siberians; 2) Beringia was probably not the only entrance of people to America: Pacific Ocean boat trips may have contributed to the HLA genetic American profile (or the opposite could also be true); 3) Amerindians entrance to America may have been different to that of Athabaskans and Eskimos and Amerindians may have been in their lands long before Athabaskans and Eskimos because they present and altogether different set of HLA-DRB1 allele frequencies; 4) Amerindians show very few "particular alleles", almost all are shared with other Amerindians, Athabaskans and Pacific Islanders, including East Australians and Siberians; 5) Our results do not support the three waves model of American peopling, but another model where the people entrance is not only Beringia, but also Pacific Coast. Reverse migration (America to Asia) is not discarded and different movements of people in either direction in different times are supported by the Athabaskan population admixture with Asian-Pacific population and with Amerindians, 6) HLA variability is more common than allele veriability in Amerindians. Finally, it is shown that gene genealogy analises should be completed with allele frequency analyses in population relatednes and migrations studies.     

Amerindian Helicobacter pylori strains go extinct, as european strains expand their host range

We studied the diversity of bacteria and host in the H. pylori-human model. The human indigenous bacterium H. pylori diverged along with humans, into African, European, Asian and Amerindian groups. Of these, Amerindians have the least genetic diversity. Since niche diversity widens the sets of resources for colonizing species, we predicted that the Amerindian H. pylori strains would be the least diverse. We analyzed the multilocus sequence (7 housekeeping genes) of 131 strains: 19 cultured from Africans, 36 from Spanish, 11 from Koreans, 43 from Amerindians and 22 from South American Mestizos. We found that all strains that had been cultured from Africans were African strains (hpAfrica1), all from Spanish were European (hpEurope) and all from Koreans were hspEAsia but that Amerindians and Mestizos carried mixed strains: hspAmerind and hpEurope strains had been cultured from Amerindians and hpEurope and hpAfrica1 were cultured from Mestizos. The least genetically diverse H. pylori strains were hspAmerind. Strains hpEurope were the most diverse and showed remarkable multilocus sequence mosaicism (indicating recombination). The lower genetic structure in hpEurope strains is consistent with colonization of a diversity of hosts. If diversity is important for the success of H. pylori, then the low diversity of Amerindian strains might be linked to their apparent tendency to disappear. This suggests that Amerindian strains may lack the needed diversity to survive the diversity brought by non-Amerindian hosts.     

Molecular surveillance of HIV-1 in Madrid, Spain: a phylogeographic analysis

The molecular epidemiology of HIV-1 is constantly changing, mainly as a result of human migratory flows and the high adaptive ability of the virus. In recent years, Spain has become one of Europe''s main destinations for immigrants and one of the western European countries with the highest rates of HIV-positive patients. Using a phylogeographic approach, we have analyzed the relationship between HIV-1 variants detected in immigrant and native populations of the urban area of Madrid. Our project was based on two coincidental facts. First, resistance tests were extended to naïve and newly diagnosed patients, and second, the Spanish government legislated the provision of legal status to many immigrants. This allowed us to obtain a large data set (n = 2,792) from 11 Madrid hospitals of viral pol sequences from the two populations, and with this unique material, we explored the impact of immigration in the epidemiological trends of HIV-1 variants circulating in the largest Spanish city. The prevalence of infections by non-B HIV-1 variants in the studied cohort was 9%, rising to 25% among native Spanish patients. Multiple transmission events involving different lineages and subsubtypes were observed in all the subtypes and recombinant forms studied. Our results also revealed strong social clustering among the most recent immigrant groups, such as Russians and Romanians, but not in those groups who have lived in Madrid for many years. Additionally, we document for the first time the presence of CRF47_BF and CRF38_BF in Europe, and a new BG recombinant form found in Spaniards and Africans is tentatively proposed. These results suggest that the HIV-1 epidemic will evolve toward a more complex epidemiological landscape.     

Analysis of HLA class II haplotypes in the Cayapa Indians of Ecuador: a novel DRB1 allele reveals evidence for convergent evolution and balancing selection at position 86.

PCR amplification, oligonucleotide probe typing, and sequencing were used to analyze the HLA class II loci (DRB1, DQA1, DQB1, and DPB1) of an isolated South Amerindian tribe. Here we report HLA class II variation, including the identification of a new DRB1 allele, several novel DR/DQ haplotypes, and an unusual distribution of DPB1 alleles, among the Cayapa Indians (N = 100) of Ecuador. A general reduction of HLA class II allelic variation in the Cayapa is consistent with a population bottle-neck during the colonization of the Americas. The new Cayapa DRB1 allele, DRB1*08042, which arose by a G-->T point mutation in the parental DRB1*0802, contains a novel Val codon (GTT) at position 86. The generation of DRB1*08042 (Val-86) from DRB1*0802 (Gly-86) in the Cayapa, by a different mechanism than the (GT-->TG) change in the creation of DRB1*08041 (Val-86) from DRB1*0802 in Africa, implicates selection in the convergent evolution of position 86 DR beta variants. The DRB1*08042 allele has not been found in > 1,800 Amerindian haplotypes and thus presumably arose after the Cayapa separated from other South American Amerindians. Selection pressure for increased haplotype diversity can be inferred in the generation and maintenance of three new DRB1*08042 haplotypes and several novel DR/DQ haplotypes in this population. The DPB1 allelic distribution in the Cayapa is also extraordinary, with two alleles, DPB1*1401, a very rare allele in North American Amerindian populations, and DPB1*0402, the most common Amerindian DPB1 allele, constituting 89% of the Cayapa DPB1.(ABSTRACT TRUNCATED AT 250 WORDS)