Manuel Martin-Villa

Allelic diversity at the primateMhc-G locus: Exon 3 bears stop codons in allCercophitecinae sequences

Twenty-seven major histocompatibility complex (Mhc)-G exon 2, exon 3, and exon 2 and 3 allelic sequences were obtained together with 12 different intron 2 sequences.Homo sapiens, Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus, Macaca fascicularis, Macaca mulatta, andCercopithecus aethiops individuals were studied. Polymorphism does not follow the classical pattern of three hypervariable regions per domain and is found in all species studied; exon 3 (equivalent to the α2 protein domain) shows stop codons in theCercopithecinae group but not in thePongidae and human groups. Dendrograms show that cotton top tamarin (Saguinus oedipus) Mhc-G sequences are closer toHomo sapiens andPongidae than toCercopithecinae, probably due to the stop codons existing at exon 3 of the latter. There is a clear trans-species evolution of allelism inCercopithecinae and also in exon 2 of all the other apes studied, but a generation of allelism within each species may be present on exon 3 sequences. This discrepancy may be due to the preferential use of exon 2 over exon 3 at the mRNA splicing level within each species in order to obtain the appropriate functional G product.Mhc-G intron 2 shows conserved motifs in all species studied, particularly a 23 base pair deletion between positions 161 and 183 which is locus specific, and some of the invariant residues, important for peptide presentation, conserved in classical class 1 molecules from fish and reptiles to humans were not found inMhc-G alleles; the intron 2 Dendrogram also shows a particular pattern of allelism within each species. In summary,Mhc-G has substantial differences from other classical class I genes: polymorphism patterns, tissue distribution, gene structure, splicing variability, and probably an allelism variability within each species at exon 3. The G proteins may also be different. This indicates that theMhc-G function may not be peptide presentation to the clonotypic T-cell receptor.

Different evolutionary pathway of B*570101 and B*5801 (B17 group) alleles based in intron sequences.

AbstractTwo theories about MHC allele generation have been put forward: (1) point mutation diversification and/or (2) gene conversion events. A model supporting the existence of both of these mechanisms is shown in this paper; the possible evolution of the HLA-B*570101 and HLA-B*5801 alleles (which belong to the HLA-B17 serology group) is studied. The hypothesis favoured is that gene conversion events have originated these alleles, because intron sequences are also analysed. Evolution by point mutation should only be accepted if flanking introns have also been sequenced.

Ancestry of Amerindians and its Impact in Anthropology, Transplantation, HLA Pharmacogenomics and Epidemiology by HLA Study in Wiwa Colombian Population

RESEARCH ARTICLE Ancestry of Amerindians and its Impact in Anthropology, Transplantation, HLA Pharmacogenomics and Epidemiology by HLA Study in Wiwa Colombian Population Antonio Arnaiz-Villena, Ester Muñiz, Jose del Palacio-Gruber, Cristina Campos, Javier Alonso-Rubio, Eduardo Gomez-Casado, Filogonio Lopez-Pacheco, Manuel Martin-Villa and Carlos Silvera Department of Immunology, University Complutense, School of Medicine, Madrid Regional Blood Center, Madrid, Spain Department of Inmunología Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Autopista A6, Hipódromo, Madrid, Spain Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico Universidad del Norte, Barranquilla, Colombia

Genetic HLA Study of Kurds in Iraq, Iran and Tbilisi (Caucasus, Georgia): Relatedness and Medical Implications.

Kurds from Iraq (Dohuk and Erbil Area, North Iraq) have been analyzed for HLA genes. Their HLA genetic profile has been compared with that of other Kurd groups from Iran and Tbilisi (Georgia, Caucasus) and also Worldwide populations. A total of 7,746 HLA chromosomes have been used. Genetic distances, NJ dendrograms and correspondence analyses have been carried out. Haplotype HLA-B*52—DRB1*15 is present in all three analyzed Kurd populations. HLA-A*02-B*51-DRB1*11 is present in Iraq and Georgia Kurds. Haplotypes common to Iran and Iraq Kurds are HLA DRB1*11—DQB1*03, HLA DRB1*03—DQB1*02 and others in a lower frequency. Our HLA study conclusions are that Kurds most probably belong to an ancient Mediterranean / Middle East / Caucasian genetic substratum and that present results and those previously obtained by us in Kurds may be useful for Medicine in future Kurd transplantation programs, HLA Epidemiology (HLA linked diseases) and Pharmacogenomics (HLA-associated drug side effects) and also for Anthropology. It is discussed that one of the most ancient Kurd ancestor groups is in Hurrians (2,000 years BC).

HLA genes in Atlantic Celtic populations: are Celts Iberians?

Atlantic Europe populations were analyzed with HLA genes in order to establish their relationship among themselves and with other populations. Standard genetic and statistical software analyses were used. Celtic populations (British Isles and French Bretons) have genetically been found close together: Irish, Welsh, Orkney Islanders (Scottish), French Bretons, Galicians, Spanish Basques, Portuguese, cluster together in DA genetic distances, correspondence analysis and Neighbour Joining dendrograms. Genetics have been shown by itself not suffice to determine populations migration/relatedness. Aristotle and Herodotus placed Celts in Iberia and R1b chromosome Y marker is high in Iberia and all Celtic European populations above mentioned (probably stemming from Iberian Ice refugee after Last Glaciation) and Ancient Celt language (Gaelic) is being translated from Iberian-Tartesian language: these suggest that Celts and Iberians, so named by Classic authors, constitute the same population. On the other hand, a) R1b gene analysis of Canary Islands ancient inhabitants (Guanches), b) abundant Iberian scripts are also found in Canary Islands, c) a established North Africa/Iberia ancient gene flow, and d) no evidence of demic diffusion from eastern to western Mediterranean according to human ancient skeleton studies is noticed in Mesolithic/Neolithic transition: these facts suggest that ancient Canary Islanders may be included within the Iberian/Celtic population. Our conclusions are that: 1) Celts are concentrated in Atlantic Europe, 2) Iberians and Celts mentioned by classic authors most probably refer to the same population living in Iberian Peninsula (Spain/Portugal); in addition, North African Berbers and ancient Canary Islanders also belong to this group 3) Postulated farmers demic diffusion in a East to West Mediterranean direction never existed. Keywords: Celts, Iberians, Picts, Scottish, Orkney Islands, Irish, British (English), French Bretons, Welsh, Basques, Galicians, Canary Islands, Mediterranean demic diffusion, Gaelic language