HLA study in Mexico Nahua/Aztec Amerindians: Close relatedness to the ancient Central America ethnic groups.

Nahua population (also named Aztec or Mexica) was studied for HLA class II genes in a Mexican rural city (Santo Domingo Ocotitlan, Morelos State) belonging to the nowadays Náhuatl speaking areas in Mexico. The most frequent HLA class II alleles were typical Amerindian (HLA-DRB1*04:07, DQB1*03:01 DRB1*04:03 or DRB1*04:04) and also were some calculated extended haplotypes (HLA-DRB1*04:07-DQB1*03:02,DRB1*08:02-DQB1*04:02, or DRB1*10:01-DQB1*05:01 among others). When using HLA-DRB1 Neís genetic distances, our isolated Nahua population was found to be close to other Central America Amerindians like the ancient-established Mayans or Mixe. This may suggest that Nahuas origin was also from Central America. It contrasts to legend that assumes they came from the North, and they built the Aztec Empire after submitting Central America neighbouring ethnic groups before 1519 CE when Spaniards led by Hernán Cortés arrived to Mexico.

HLA-G in Mayas from Yucatan: An evolutionary approach.

HLA-G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA sequencing technique. It is described that Mayas are probably one of the first populations together with Olmecs that populated Meso America and that important HLA genetic differences between Mexican and Guatemalan Mayas support that Maya languages were imposed to several neighbouring Amerindian groups. HLA-G*01:01:02, HLA-G*01:01:01 and HLA-G*01:04:01 are the most frequent alleles in this population. It is remarkable that HLA-G*01:05N allele was not found in the population in accordance with similar results found in another Amerindians. Also, protein allele HLA-G*01:04 frequency is found not to differ to those found in another far or close living Amerindians in contrast to other World populations. It seems that while high HLA-G*01:05N frequency is found in Iran and Middle East populations, probably where this allele appeared within an ancestral HLA-A*19 group of alleles haplotype and it is maintained by unknown evolutionary forces, Amerindians do not have a high frequency because a founder effect or because required natural evolutionary forces do not exist in America. Finally, we believe useful to study HLA-G evolution for its physiopathology understanding in addition to the many papers on statistics on HLA-G and in vitro models that are yearly published.

Frequencies and significance of HLA genes in Amerindians from Chile Cañete Mapuche.

Mapuche Amerindians live now widespread in Central South Chile and Argentina and speak "Mapudungun", an unclassified language. A group of Chilean Mapuche was studied for HLA genes using standard techniques. Typical Amerindian HLA genes and haplotypes are found in the population, like HLA-DRB1*14:02, -08:02 and class II haplotype DRB1*08:02-DQB1*04:02. However, these and other genes are also common in Pacific Islanders. Thus, relatedness of First America Inhabitants with some Pacific Islanders is stressed. Evidences of Pacific and Atlantic cultural and genetic exchange, probably in both directions, and California Man settlements found since 130,000 years ago makes it necessary a revision of Americas peopling. This study may be also useful for medical Mapuche use in Transplantation and HLA and disease Epidemiology.

HLA in Uros from Peru Titikaka Lake: Tiwanaku, Easter and Pacific Islanders.

Uros people live in floating reed islands in Titikaka Lake in front of Puno town (Peru). They could have started Tiwanaku culture and shared genes and culture with Pacific Islanders; it is particularly relevant the giant hat covered men statues found in both Tiwanaku at Titikaka Lake shore and Easter Island (3700 km far from Chile in Pacific Ocean). These giants monoliths are very similar one another and unique in America and Pacific Islands. The following HLA alleles are shared in a specifically high frequency between Uros and Pacific Islanders : HLA-A*24:02, HLA-B*35:05, HLA-B*48:01, HLA-DRB1*04:03, HLA-DRB1*08:02 and HLA-DRB1*09:01. Uros also have 3 unique HLA haplotypes: A*24:02-B*15:04 - DRB1*14:02-DQB1*03:01, A*68:01:02-B*35:05-DRB1*04:03-DQB1*03:02, A*24:02-B*48:01-DRB1*04:03-DQB1*03:02. Also Uros seem to be one of the most ancient population in Titikaka Lake that could have started Tiwanaku culture. Prehistoric contacts between Amerindians and Pacific Islanders are strongly suggested by genetic and cultural traits. It is not discarded that Uros could have come from Pacific Islands: Uros show melanic skin and are dolichocephalic; in contrast, surrounding Aymara people have a clear skin and are brachicephalic. The Kon-Tiki project led by Thor Heyerdahl showed that a simple sailing is possible between Peru and Polynesia Islands; also, the most ancient skull found in America is of black origin: Luzia, suggesting that first America peopling was also carried out by Black/coloured people.

HLA in Colombia Wayu from Guajira Peninsula Amerindians: Pacific Ocean relationships.

Wayu Amerindians live around Guajira Peninsula shared by Colombia and Venezuela. Wayu from Colombia have been studied for their HLA profile and these data put in context with both genetic and cultural relatedness to Pacific Islanders. HLA-A*24 and HLA-B*35 (most likely HLA-A*24:02 and HLA-B*35:05) and HLA-DRB1*04:03 and HLA-DQB1*03:02 are shared both by Wayu and other Amerindians and Pacific Islanders in specific high frequency. Our findings further suggest a genetic relationship between Amerindians (also Wiwa/Arsario and Chimila from Colombia; Uros from Peru) and Pacific Islanders. Titikaka Lake (Peru/Bolivia) Amerindians (Aymara, Uros and Quechua) share also cultural traits, like Tiwanaku (Titikaka Culture giant statues) and Easter Island Culture giant statues or "Moais".

The first free Africans in America: HLA study in San Basilio de Palenque (Colombia).

Original San Basilio de Palenque population (North Colombia) fled from Spanish traders that carried them as slaves and they funded in nearby Maria Mountains a fortified town (Palenque). They started helping new Africans brought as slaves to flee and join them. Most of them spoke a Bantu-Congo language and nowadays they speak the only one extant Bantu-Spanish Creole language. Spanish Crown was forced to issue a decree declaring them free (1691 CE), more than 100 years before than Haiti Republic existed. HLA-A, -B, -DRB1 and -DQB1 alleles were studied and further computer procedures were performed with Arlequin 3.5 software. No Amerindian or Europeans gene flow to this population was found. However, three specific HLA extended haplotypes are found in this population, which may reflect an isolation from other Africans or Afro-Americans also. This may be due to the maintenance of their own African culture, and even their unique Creole language.

HLA genes in Barranquilla (North Colombia): Searching for cryptic Amerindian genes.

America First Inhabitants population (Amerindians, Na Dene and Eskimos) underwent a drastic population reduction and gene exchange after Europeans and Africans arrival after 1492 AD. Barranquilla population may be a good model to study present day population admixture in South America. HLA-A, -B and -DRB1 DNA typing has been performed in 188 unrelated individuals originated in the area and speak Spanish language; they showed apparent European/African and mixed characters. HLA genetic European/African features were found and only 1.85% Amerindian one. This contrasts with neighboring Cuban population where 10% HLA Amerindian characters appear.

HLA-G, -A haplotypes in Amerindians (Ecuador): HLA-G*01:05N World distribution.

HLA-G and HLA-A frequencies have been analysed in Amerindians from Ecuador. HLA-G allele frequencies are found to be closer to those of other Amerindians (Mayas from Guatemala and Uros from Peru) and closer to European ones than to Far East Asians groups, particularly, regarding to HLA-G*01:04 allele. HLA-G/-A haplotypes have been calculated for the first time in Amerindians. It is remarkable that HLA-G*01:05N "null" allele is found in a very low frequency (like in Amerindian Mayas and Uros) and is also found in haplotypes belonging to the HLA-A19 group of alleles (HLA-A*30, -A*31, -A*33). It was previously postulated that HLA-G*01:05N appeared in HLA-A*30/-B*13 haplotypes in Middle East Mediterraneans. It may be hypothesized that in Evolution, HLA-G*01:05N existed primarily in one of the HLA extant or extinct -A19 haplotype, whether this haplotype was placed in Middle East or other World areas, including America. However, the highest present day HLA-G*01:05N frequencies are found in Middle East Mediterraneans.

Characterisation and functional implications of the two new HLA-G alleles found in Amerindian and Caribbean populations.

HLA-G polymorphism has been found to be relatively low in all world populations. In the present paper two new HLA-G molecules are described in ancient American natives. A new HLA-G molecule from a Ecuador Amerindian individual (male) showed four codon changes with respect to HLA-G*01:01:01. Silent changes at α1 domain (residue 57, Pro, CCG→CCA) and α2 domain (residue 93, His, CAC→CAT and residue 100, Gly, GGC→GGT) and one productive change in α3 domain (residue 219 changed from Arg to Trp). This α3 change may dramatically alter HLA-G interactions with beta-2 microglobulin, CD8, ILT-2 and ILT-4 ligands present in subsets of T, B, NK, monocytes, macrophages and dentritic cells. Another HLA-G new molecule was found in a woman from Hispaniola Island, Dominican Republic (Sto Domingo): it presented a silent change at α2 domain residue 107, Gly, GGA→GGT and non-silent change at residue 178, Met→Thr (with respect to HLA-G*01:01:01) which is close to class I molecule/clonotypic T cell receptor interaction sites. Functional implications of these findings are discussed.

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.