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

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes

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

spa: Los primeros habitantes y el poblamiento de América todavía se debaten. Para aumentar el conocimiento sobre estas cuestiones, nos hemos propuesto detectar genes HLA de una comunidad amerindia aislada: Jaidukama, que vive en la selva ecuatorial del norte de Colombia. Se realizaron cálculos de genotipado HLA y haplotipo extendido en 39 individuos sanos pertenecientes a 13 familias. Las frecuencias de HLA se compararon con otras poblaciones amerindias y de todo el mundo mediante el cálculo de distancias genéticas, dendrogramas de parentesco y análisis de correspondencia. Solo se encontraron cuatro alelos DRB1 (*0404, *0407, *1402 y *1602); sin embargo, se contaron directamente un total de 17 haplotipos HLA de clase I-clase II amerindios diferentes a partir de los estudios familiares, nueve de ellos eran específicos de Jaidukamas. Algunos de los alelos o grupo de alelos dentro de un haplotipo extendido (es decir, DQB1–DRB1) también se encontraron en asiáticos e isleños del Pacífico, lo que respalda aún más la existencia de un flujo de genes asiáticos y del Pacífico con amerindios o un efecto fundador común. Se apoya además que los haplotipos HLA extendidos varían más rápido que los alelos en las poblaciones. Se concluye que este modelo único de estudio de familias aisladas amerindias sugiere que la variación rápida de haplotipos HLA puede ser más importante que la variación de alelos para la supervivencia (respuestas inmunitarias iniciales). Este trabajo también puede ser útil para futuros programas de trasplantes en el área. Se concluye que este modelo único de estudio de familias aisladas amerindias sugiere que la variación rápida de haplotipos HLA puede ser más importante que la variación de alelos para la supervivencia (respuestas inmunitarias iniciales). Este trabajo también puede ser útil para futuros programas de trasplantes en el área. Se concluye que este modelo único de estudio de familias aisladas amerindias sugiere que la variación rápida de haplotipos HLA puede ser más importante que la variación de alelos para la supervivencia (respuestas inmunitarias iniciales). Este trabajo también puede ser útil para futuros programas de trasplantes en el área.eng: 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