Subject(s)
Celiac Disease/complications , Hematologic Diseases/etiology , Brain Diseases/etiology , Child , HumansABSTRACT
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.
Subject(s)
HLA Antigens/genetics , Indians, South American/genetics , Alleles , Gene Frequency , Genetic Variation , Genotype , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DQ Antigens/genetics , HLA-DQ beta-Chains , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Haplotypes/genetics , Humans , PeruABSTRACT
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.
Subject(s)
Ethnicity/genetics , Gene Frequency/genetics , HLA Antigens/genetics , Haplotypes/genetics , Alleles , Genetic Variation , Genetics, Population , Humans , PortugalABSTRACT
The non-classical human leucocyte antigen (HLA) class I locus, HLA-G, shows a low protein polymorphism and a more varied DNA (eight proteins and 28 alleles). HLA-G DNA polymorphism accounts mainly for changes at third codon bases of the protein coding exons; this does not imply amino acid change in most cases. This relatively high HLA-G DNA polymorphism in comparison with their protein polymorphism suggests that evolutionary forces are acting upon HLA-G for invariance. This may be related to the immunotolerogenic function postulated for HLA-G.
Subject(s)
HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Polymorphism, Single Nucleotide , Alleles , Amino Acid Sequence , Base Sequence , DNA/genetics , Exons , HLA-G Antigens , Humans , Molecular Sequence Data , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Terminology as TopicABSTRACT
HLA-G non classical class I locus shows a comparatively low polymorphism. It encodes for tolerogenic HLA molecules that may be important in autoimmunity and transplant (and foetal) rejection control. HLA-G molecules give negative signals to Natural Killer and T lymphocytes. In the present paper, a new allele, HLA-G*08, is described, which may be useful for monitoring transplants and for HLA and disease studies.
Subject(s)
Amino Acid Substitution/genetics , HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , HLA Antigens/chemistry , HLA-G Antigens , Histocompatibility Antigens Class I/chemistry , Humans , Protein Structure, Tertiary/geneticsABSTRACT
Human leukocyte antigen (HLA)-E is a nonclassical class I (Ib) gene with a restricted polymorphism. Only eight DNA alleles and three proteins of this gene have been described and their frequencies analyzed in Caucasian, Oriental, Asian Indian, and Negroid populations. In the present study, HLA-E polymorphism has been analyzed in six Amerindian and Mestizo populations from North and South America and compared with previously described populations. HLA-E*0101 is the most frequent allele found in all populations except in Afrocolombian and Wayu Amerindians, in which blood group analyses show a high admixture with Caucasian and African populations. Mazatecan and Mapuche (two Amerindian groups from North and South America, respectively) presented similar HLA-E frequencies, whereas Wayu Indians are more similar to the Afrocolombian population. The Mexican and Colombian Mestizo show similar allele frequencies to Amerindians with high frequencies of HLA-E*0101 and HLA-E*010302 alleles. Also, frequencies in Negroids and Asian Indians present a similar distribution of HLA-E alleles. These data are in agreement with worldwide restricted polymorphism of HLA-E because no new allele was detected in the six populations studied. The allelic frequencies show differences among Caucasian, Oriental, Mestizo and Indian populations. Ape major histocompatibility complex-E allelism is also very restricted: common chimpanzee (one allele); bonobo (two alleles); gorilla (two alleles); orangutan (one allele); rhesus monkey (eight alleles); cynomolgus monkey (two alleles); and green monkey (two alleles).
Subject(s)
Asian People/genetics , Ethnicity/genetics , HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Polymorphism, Genetic , White People/genetics , Alleles , Animals , Chile/ethnology , Colombia/ethnology , Gene Frequency , Hominidae/genetics , Humans , Mexico , Pan paniscus/genetics , Pongo pygmaeus/genetics , Protein Conformation , HLA-E AntigensABSTRACT
Six proteins, one null allele and 22 human leukocyte antigen (HLA)-G alleles were found in humans. Bonobo, chimpanzee and gorilla only show one allele and orangutan shows five alleles. All Cercopithecus alleles show stop codons at position 164 (Macaca mulatta with seven DNA alleles, Macaca fascicularis with seven DNA alleles and Cercopithecus aethiops with three DNA alleles). Cotton-top tamarin New World monkeys showed 20 DNA and protein alleles; the major histocompatibility complex (MHC)-G New World sequences seem to be closer to MHC-E and lack typical MHC-G primates intron 2-specific deletion. This seems to suggest that MHC-G genes in New World primates are not orthologous and that their function may be similar to that of classical presenting MHC genes.
Subject(s)
Biological Evolution , HLA Antigens/genetics , Histocompatibility Antigens Class I/genetics , Major Histocompatibility Complex/genetics , Polymorphism, Genetic , Animals , Base Sequence , Family , Female , HLA-G Antigens , Homozygote , Humans , Major Histocompatibility Complex/immunology , Male , Molecular Sequence Data , Pedigree , Primates/genetics , Sequence Homology, Nucleic AcidABSTRACT
HLA class I and class II alleles have been studied in 60 unrelated people belonging to Mayos ethnic group, which lives in the Mexican Pacific Sinaloa State. Mayos HLA profile was compared to other Amerindians and worldwide populations' profile. A total of 14,896 chromosomes were used for comparisons. Genetic distances between populations, Neigbour-Joining dendrograms and correspondence analyses were performed to determine the genetic relationship among population. The new specific Mayo HLA haplotypes found are: HLA-A*02-B*35-DRB1*1406-DQB1*0301; HLA-A*02-B*48-DRB1*0404-DQB1*0302; HLA-A*24-B*51-DRB1*0407-DQB1*0302 and HLA-A*02-B*08-DRB1*0407-DQB1*0302. However, the typical Meso American HLADRB1*0407 represents a 40% of all DRB1 alleles. While common HLA characteristics are found in Amerindian distant ethnic groups, still new group specific HLA haplotypes are being found, suggesting that a common founder effect (i.e. high DRB1*0407) is noticed. Moreover, new HLA haplotypes are almost certainly appearing along time probably due to specific pathogen (?) selection for diversity. Mayo language is close to the Tarahumara one (another geographically close group); notwithstanding both groups are not genetically close according to our results, showing again the different evolution of genes and languages, which do not correlate. Finally, Sinaloa is one of the Mexican States in which more European genes are found. However, the results presented in this paper, where no European HLA genes are seen in Mayos, should have a bearing in establishing transplant programs and in HLA and disease studies.
ABSTRACT
The major histocompatibility complex class I genes comprise a bunch of classical genes (A, B, C), non-classical genes (E, F and G), pseudogenes and truncated genes. MHC-E, -F and -G are now considered immune "tolerization" molecules, which not only interact with NK cells but with T lymphocyte subsets and other cells and have a role in fetus acceptation. A strong positive directional selection is acting for maintaining the observed low polymorphism on E, F and G loci in human and apes. Invariance must be important for this non-classical class I proteins function.
Subject(s)
HLA Antigens/genetics , HLA Antigens/immunology , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Alleles , Animals , Base Sequence , DNA Primers/genetics , Evolution, Molecular , Female , Fetus/immunology , Genetic Variation , HLA Antigens/chemistry , HLA-G Antigens , Histocompatibility Antigens Class I/chemistry , Humans , Immune Tolerance , Models, Molecular , Pregnancy , Primates/genetics , Primates/immunology , HLA-E AntigensABSTRACT
El estudio de la genética de poblaciones se utiliza en epidemiologíay en medicina preventiva y predictiva, además de paraaveriguar el origen y el emparentamiento de los grupos étnicosen estudios antropológicos.El sistema más polimórfico en humanos es el complejo HLA,y unos pocos de sus alelos están ligados a enfermedad. En este sentido,los marcadores genéticos más utilizados para estudios antropológicos,las variantes de DNA mitocondrial y del cromosoma Y,también están ligadas a enfermedades, pero en un grado comparativamentemayor que HLA, teniendo en cuenta solamente elnumero de «alelos sanos» de estos marcadores genéticos. El estudiode los genes HLA demuestra que es muy útil para descubrir elorigen y el emparentamiento genético de las poblaciones a nivelmundial. En el presente estudio, hemos comprobado cómo, aparentemente,los Amerindios no se relacionan genéticamente conninguna otra población del mundo. De acuerdo con los genes HLA,los Amerindios son los primeros habitantes de las Américas y estabanallí cuando llegaron oleadas de gentes hablando lenguas NaDene (Atabascos, Navajos, Apaches) y Esquimales. Mientras seobserva que en todas las otras poblaciones mundiales existe ungradiente de emparentamiento, que va en general concordandocon la proximidad o lejanía geográfica, los Amerindios se sitúanaparte de todos. Esta conclusión principal se ha basado en el estudiode 14.968 cromosomas HLA de todo el mundo y en análisisestadísticos utilizando el método de «Neighbour Joining» y los análisisde correspondencia, junto con las distancias genéticas de Neientre grupos étnicos. El estudio poblacional HLA de Amerindiosprocedentes de la zona del Océano Pacífico sudamericano es particularmenteimportante para España, donde se viene registrandoun importante flujo migratorio procedente de estos países. Estohace necesario hacer listas de tipaje HLA con el objeto de efectuartrasplantes entre españoles y Amerindios para fines terapeúticos
The genetic profiles of human populations are being used forepidemiology and preventive/predictive medicine, in additionto ascertaining the origin and relatedness of ethnic groups foranthropological studies.HLA is the most polymorphic genetic system in humans anda few HLA alleles are linked to disease. However, the mtDNAand Chr Y variants, widely used in genetic anthropology, are linkedto disease to a much higher degree than HLA, if we only takeinto account the number of «healthy» alleles from these three differentgenetic markers.HLA gene studies allow the determination of the origin andgenetic relatedness of worldwide populations. In the present studywe have been able to uncover that Amerindians apparently donot relate with any other worldwide population, according totheir HLA genetic profile. Amerindians are the very First AmericanNatives that were already in America when Na Dene (Athabascans,Navajo, Apache) and Eskimo speaking people reachedit. While other worldwide populations are genetically related followinggenerally a smooth geographic gradient, Amerindians appearapart. This main conclusion has been reached by using 14,968worldwide HLA chromosomes and Neighbour Joining and correspondenceanalyses together with Nei´s genetic distances betweenethnic groups. The HLA study of southern American PacificAmerindians is particularly important for Spain, where a recentimportant immigration of these populations has taken place. Thismakes it necessary to building up an Amerindian typing list inSpain in order to deal with transplantation between Spaniardsand Amerindians for therapeutic uses
Subject(s)
Humans , American Indian or Alaska Native/genetics , Major Histocompatibility Complex/genetics , Ethnicity/genetics , Inuit/genetics , Diabetes Mellitus, Type 1/genetics , Organ Transplantation/ethnologyABSTRACT
The major histocompatibility complex (MHC)-F class Ib locus shows a limited polymorphism, and the function of its mainly intracellular protein is not clear. We have identified human leucocyte antigen (HLA)-F orthologous DNA sequences in Pongidae in order to study the MHC-F gene evolution and its products' function. HLA-F orthologous cDNA transcripts are found in chimpanzee and in the new primate species studied (bonobo, gorilla and orangutan). Analyses of the predicted amino acid sequences and their comparison with other primate MHC-F proteins show that MHC-F may be a protein with a typical class I structure and that the key residues of the peptide-binding region (PBR) are highly conserved in MHC-F in all studied primates species. Thus, MHC-F conservation along the primate evolution suggests an important role in cellular physiology. It is possible that the MHC-F protein could be involved, together with MHC-G and MHC-E, in the natural killer (NK) cell activity regulation, although rhesus macaque does not express MHC-G and MHC-E orthologues. The evolutionary pathway of the six-base-pair deletion at exon 2 existing in some primates is put forward.
Subject(s)
Evolution, Molecular , Exons/genetics , Genes, MHC Class I/genetics , Quantitative Trait Loci/genetics , Sequence Deletion/genetics , Amino Acid Sequence , Animals , Cell Line , Exons/immunology , Genes, MHC Class I/immunology , Hominidae , Humans , Molecular Sequence Data , Quantitative Trait Loci/immunology , Sequence Analysis, Protein/methods , Sequence Deletion/immunologyABSTRACT
Aymara Amerindians from the Titicaca Lake Andean highlands are studied for HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 gene frequencies. Genetic distances, neighbour-joining and correspondence analyses are performed by using other Amerindian and worldwide populations (15384 chromosomes are studied). The HLA genetic profile of Aymaras is different from neighbouring and language-related Quechuas (Incas). Both Quechuas and Aymaras seem to present an HLA-DRB1*0901 high frequency, which is present in a very low frequency or absent in Mesoamericans (Mazatecans, Mayans) and most studied Amerindians. Moreover, it is observed a closer relatedness of Aymaras with Amerindians from the Amazon Basin and Chaco lowlands, compared to Quechuans.
