Different patterns of Toll-like receptor 2 polymorphisms in populations of various ethnic and geographic origins

Upon the invasion of the host by microorganisms, innate immunity is triggered through pathogen recognition by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are the best-studied class of PRRs, and they recognize specific pathogen-associated molecular patterns (PAMPs) from various microorganisms. A large number of studies have shown that genetic variation in TLRs may influence susceptibility to infections. We assessed the genetic variation of TLR2, which encodes one of the most important TLRs, in various populations around the globe and correlated it with changes in the function of the molecule. The three best-known nonsynonymous TLR2 polymorphisms (1892C>A, 2029C>T, and 2258G>A) were assessed in different populations from the main continental masses: Romanians, Vlax-Roma, Dutch (European populations), Han Chinese (East Asia), Dogon, Fulani (Africa), and Trio Indians (America). The 2029C>T polymorphism was absent in both European and non-European populations, with the exception of the Vlax-Roma, suggesting that this polymorphism most likely arose in Indo-Aryan people after migration into South Asia. The 1892C>A polymorphism that was found exclusively in European populations, but not in Asian, African, or American volunteers, probably occurred in proto-Indo-Europeans. Interestingly, 2258G>A was present only in Europeans, including Vlax-Roma, but at a very low frequency. The differential pattern of the TLR2 polymorphisms in various populations may explain some of the differences in susceptibility to infections between these populations.     

Ancestry informative markers in Amerindians from Brazilian Amazon.

Ancestry informative markers (AIMs) are genetic loci with large frequency differences between the major ethnic groups and are very useful in admixture estimation. However, their frequencies are poorly known within South American indigenous populations, making it difficult to use them in admixture studies with Latin American populations, such as the trihybrid Brazilian population. To minimize this problem, the frequencies of the AIMs FY-null, RB2300, LPL, AT3-I/D, Sb19.3, APO, and PV92 were determined via PCR and PCR-RFLP in four tribes from Brazilian Amazon (Tikúna, Kashinawa, Baníwa, and Kanamarí), to evaluate their potential for discriminating indigenous populations from Europeans and Africans, as well as discriminating each tribe from the others. Although capable of differentiating tribes, as evidenced by the exact test of population differentiation, a neighbor-joining tree suggests that the AIMs are useless in obtaining reliable reconstructions of the biological relationships and evolutionary history that characterize the villages and tribes studied. The mean allele frequencies from these AIMs were very similar to those observed for North American natives. They discriminated Amerindians from Africans, but not from Europeans. On the other hand, the neighbor-joining dendrogram separated Africans and Europeans from Amerindians with a high statistical support (bootstrap = 0.989). The relatively low diversity (G(ST) = 0.042) among North American natives and Amerindians from Brazilian Amazon agrees with the lack of intra-ethnic variation previously reported for these markers. Despite genetic drift effects, the mean allelic frequencies herein presented could be used as Amerindian parental frequencies in admixture estimates in urban Brazilian populations.     

Diversity and Divergence Among the Tribal Populations of India

Tribal populations of the Indian subcontinent have been of longstanding interest to anthropologists and human geneticists. To investigate the relationship of Indian tribes to Indian castes and continental populations, we analyzed 45 unlinked autosomal STR loci in 9 tribal groups, 8 castes, and 18 populations from Africa, Europe and East Asia. South Indian tribal populations demonstrate low within‐population heterozygosity (range: 0.54 – 0.69), while tribal populations sampled further north and east have higher heterozygosity (range: 0.69 – 0.74). Genetic distance estimates show that tribal Indians are more closely related to caste Indians than to other major groups. Between‐tribe differentiation is high and exceeds that for eight sub‐Saharan African populations (4.8% vs. 3.7%). Telugu‐speaking populations are less differentiated than non‐Telugu speakers (F_ST: 0.029 vs. 0.079), but geographic distance was not predictive of genetic affinity between tribes. South Indian tribes show significant population structure, and individuals can be clustered statistically into groups that correspond with their tribal affiliation. These results are consistent with high levels of genetic drift and isolation in Indian tribal populations, particularly those of South India, and they imply that these populations may be potential candidates for linkage disequilibrium and association mapping.     

Linked loci in chromosome 1 (FXIIIB,HF, PEPC) and their variability in Brazilian Indians

A total of 352 individuals living in seven localities of two Brazilian Indian groups (Macushi and Içana River Indians) were variously studied for coagulation factor XIIIB, human factor H, and a new polymorphism of peptidase C. No significant inter- or intra-tribal differences were found for the FXIIIB alleles, the frequencies varying around 95% for F13B*3 and 5% for F13B*1. Results for HF were heterogeneous, HF*A presenting a much higher frequency among the Macushi (32%) than among the Içana River Indians (9%). Intratribal differences were also found among both groups. Linkage disequilibrium exists between alleles of these two systems (0.03 ± 0.01). These are the first results for human factor H obtained among Amerindians. The data for PEPC were limited to the Içana River Indians. There is heterogeneity among the three localities sampled and evidence of moderate linkage disequilibrium between markers in this locus and in F13B (0.02 ± 0.01). © 1992 Wiley-Liss, Inc.     

HLA-DP polymorphism in Venezuelan Amerindians

Three different Venezuelan Amerindian tribes were studied for human leukocyte antigen (HLA)-DPA1 and DPB1 allelic variability using polymerase chain reaction–sequence-specific oligonucleotide probes (PCR-SSOP) and sequence-based typing in a selected group of samples. These tribes are geographically (two from the Perija Mountain range and one from the Orinoco Delta) and linguistically distinct: the Bari (from Campo Rosario and Saymaidoyi villages) and the Warao have been classified within the Chibcha linguistic family, whereas the Yucpa (from the Aroy, Marewa, and Peraya villages) are Carib speaking. Venezuelan Indians, like other Native American tribes, show a markedly reduced number of different HLA-DP alleles (range, 2–7) and haplotypes (range, 4–11) in comparison with neighboring Venezuelan mestizo and other non-Indian populations. Some HLA-DPB1 (*0402 and *1401) alleles characteristic for all Amerindian tribes are present also in these populations. Despite general similarities, each tribe and, in some cases, some subtribes show their own pattern of allele and haplotype distribution apparently more as a result of linguistic than to geographic variation.     

Hispano-Indian admixture in Paraguay studied by analysis of HLA-DRB1 polymorphism

The genetic polymorphism of the Paraguayan population results from the admixture between South American Indians named Guaranis and Spaniards. In order to evaluate the genetic predominance in the Paraguayan population, we typed 50 healthy Paraguayans for HLA-DRB1 by molecular biology and compared their HLA-DRB1 polymorphism to that of the Guaranis and of two Spanish populations. Six significant differences of alleles frequencies were observed between Paraguayans and Guaranis--DRB1*01, 06 (13, 14), 15, 16, 07--whereas only one difference was observed with the Spaniards (DRB1*14). The DRB1*14 frequency was higher in Paraguayan than in the Spanish populations essentially due to the presence of DRB1*1402 related alleles (1402,06,13). These alleles are extremely rare in the Spanish populations whereas frequent in the Guaranis from Brazil and in South American Indian tribes living in the lymitrophe regions of Paraguay (Toba, Wichi and Terena). Thus, the presence of the DRB1*1402 related alleles (6%) in the Paraguayan population constitutes the major Indian contribution to the HLA-DR polymorphism of the Paraguayan population. The genetic distances between Paraguayans and the two Spanish populations were closer (.494 and .415) than that between Paraguayans and Guaranis (.958). Altogether these results suggest the predominance of the Spanish genetic in the Paraguayan population. Historical events are discussed to explain this predominance.     

New genetic data on Amerindians from the Paraguayan Chaco

New data on 17 blood group and protein genetic systems obtained among the Ayoreo and Lengua Indians of Paraguay are presented. They include the first report on the red cell band‐3 protein investigated among South American Indians. This information was integrated with previous results available for these two and four other groups. Five of the six populations reside in the Chaco area, while the sixth was included as an outgroup living elsewhere in Paraguay. Four of the five Chaco tribes exhibit good genetic homogeneity, but the Ayoreo are somewhat different. The results confirm the Chaco as a distinct biological (as well as cultural and economic) region, which should be considered in evaluations of genetic variability among South American Indians. Am. J. Hum. Biol. 13:660–667, 2001. © 2001 Wiley‐Liss, Inc.     

Protein genetic studies among the Tupi-Mondé Indians of the Brazilian Amazonia

A sample of 417 individuals belonging to three Tupi-Mondé-speaking tribes (Gavião, Surui, Zoró) were variously studied in relation to 26 genetic protein systems. Previous investigations performed among the Surui in relation to some of these systems were confirmed. The three groups do not depart markedly from the genetic pattern already established for South American Indians and show low inter-ethnic admixture. When these results are combined with those from 10 other Tupi tribes, two clear geographic groupings (southeastern and northwestern) can be discerned. Using different methods to evaluate the same genetic distance matrices, different patterns of association between the Tupi-Mondé populations were obtained. The populations are probably too similar among themselves, blurring finer relationships. Am. J. Hum. Biol. 10:711–722, 1998. © 1998 Wiley-Liss, Inc.     

Genetic variation within the Tupi linguistic group: new data on three Amazonian tribes

A total of 505 individuals belonging to four populations of three Brazilian Indian tribes were variously studied in relation to 34 genetic systems, and the results were compared with South American Indian averages and five other Tupi populations. Rare variants (CdE of the Rh system, PGM211-1, Cp A-CAY1, serum cholinesterase2 C5+ and some Gm combinations) were observed with varying prevalences, and the three tribes showed different degrees of departure (28%-40% of differences of 10% or more in gene frequencies) from South American Indian averages. People from two communities who speak the same language and are labelled as belonging to the same tribe (Asurini) showed a large degree of genetic differentiation. Another of the tribes studied (Urubu-Kaapor) link through genetic distance analyses with two other tribes from the north of the continent, forming a distinct microevolutionary unit. These features emphasize the peculiarities of the genetic variation in populations with a hunter-gatherer, rudimentary agriculture type of economy.     

HLA genes in Mexican Mazatecans, the peopling of the Americas and the uniqueness of Amerindians

The HLA allele frequency distribution of the Mexican Mazatecan Indians (Olmec culture) has been studied and compared with those of other First American Natives and worldwide populations (a total of 12,100 chromosomes; 6,050 individuals from 59 different populations). The main conclusions are: 1) An indirect evidence of Olmec and Mayan relatedness is suggested, further supporting the notion that Olmecs may have been the precursors of Mayans; 2) Language and genetics do not completely correlate in microenvironmental studies; and 3) Peopling of the Americas was probably more complex than postulated by Greenberg and others (three peopling waves). Significant genetic input from outside is not noticed in Meso and South American Amerindians according to the phylogenetic analyses; while all world populations (including Africans, Europeans, Asians, Australians, Polynesians, North American Na-Dene Indians and Eskimos) are genetically related. Meso and South American Amerindians tend to remain isolated in the Neighbor-Joining, correspondence and plane genetic distance analyses.     

COL1A2 (type I collagen) polymorphisms in the Colorado Indians of Ecuador

BACKGROUND: EcoRI, MspI and RsaI restriction fragment length polymorphisms (RFLPs) of the COL1A2 (type I collagen) gene are proving to be extremely informative markers for describing human populations; therefore they hold considerable potential for anthropogenetic research. AIM: The objective of this study was to characterize at the DNA level the Colorado Indians from Ecuador, for whom only blood group frequency information is available, and to investigate their relationships with the Cayapa-another Ecuadoran Native American group belonging to the same linguistic affiliation-and other world populations. SUBJECTS AND METHODS: Colorado Indians (n = 80) were analysed for the three anthropologically informative RFLPs of the COL1A2 gene. To better define the genetic relationship between this group and other populations, principal component analysis (PCA) was performed and genetic distances were estimated. Population genetic structure was tested through analysis of molecular variance (AMOVA) by comparing haplotype frequencies. RESULTS: COL1A2 allele and haplotype frequencies showed a certain degree of heterogeneity between the two Chibchan populations of Ecuador. The AMOVA test detected a significant level of differentiation (Fst = 0.034, p = 0.0049) between Colorado and Cayapa Indians. PC and genetic distance analyses showed a clear-cut separation between African and non-African populations; within the latter, the two Native American groups were differentiated from each other. CONCLUSIONS: The present findings suggest the presence of a low level of genetic relatedness between the Colorado and the Cayapa, despite their supposed common ethnogenesis. This confirms what has been inferred from other genetic data about the high degree of heterogeneity among Native Americans, even within the same linguistic branch, thus supporting the existence of genetic sub-structure within the central and southern American populations.     

Genetic variation within the Tupi linguistic group: new data on three Amazonian tribes

A total of 505 individuals belonging to four populations of three Brazilian Indian tribes were variously studied in relation to 34 genetic systems, and the results were compared with South American Indian averages and five other Tupi populations. Rare variants (CdE of the Rh system, PGM₂ 11-1, CpA-CAY1, serum cholinesterase₂ C5 + and some Gm combinations) were observed with varying prevalences, and the three tribes showed different degrees of departure (28%–40% of differences of 10% or more in gene frequencies) from South American Indian averages. People from two communities who speak the same language and are labelled as belonging to the same tribe (Asurini) showed a large degree of genetic differentiation. Another of the tribes studied (Urubu-Kaapor) link through genetic distance analyses with two other tribes from the north of the continent, forming a distinct microevolutionary unit. These features emphasize the peculiarities of the genetic variation in populations with a hunter-gatherer, rudimentary agriculture type of economy.     

Dogrib Indians of the Northwest Territories, Canada: genetic diversity and genetic relationship among subarctic Indians

Phenotypes and gene frequencies of genes at the ABO, Rhesus, MNSs, Diego, Duffy, Kell, Kp, Kidd and P blood group systems are presented for three villages of Dogrib Indians. This population resides between Great Slave and Great Bear Lakes in the Northwest Territories of Canada. Until recently they pursued an exclusively hunting-gathering-fishing lifestyle in the subarctic forest. Maximum European admixture in the Dogrib is 8.7%. Nei's coefficient of gene diversity, GST is 0.0121. Blood group data from other Athapaskan-speaking Indians were also examined. GST for Kutchin villages is approximately 1.1%. GST obtained over five tribes of Northern Athapaskans is 0.0264, a figure slightly lower than that found in comparable groups of Mexican Indians. Overall genetic differentiation (HT) in Northern Athapaskans was greater than in the Mexicans, presumably because of high, though nonquantifiable European admixture in some of the tribes. The bulk of the genetic variability in Athapaskans exists within tribes, and then within villages of the same tribe. Genetic distance analysis with Nei's standard distance D shows that Dogrib and Kutchin Indians are very close. Geographic proximity has no significant influence on inter-tribal gene flow, but is significantly associated with intra-tribal gene flow.     

Determination of HLA class II alleles by genotyping in a Manchu population in the northern part of China and its relationship with Han and Japanese populations

Abstract: To investigate the genetic background of the black populations of Colombia and Jamaica, we determined HLA types of 78 Colombian and 98 Jamaican blacks from 2 different socioeconomic groups (Jamaican #1 and Jamaican #2) and estimated the frequencies of HLA genes and haplotypes. A phylogenetic tree based on the HLA gene frequencies revealed that Jamaican #1 and Jamaican #2 were distinct from each other, Jamaican #1 being closely related to the Colombian blacks and the Jamaican #2 being closely related to Senegalese and Zairean populations. Three-locus HLA haplotypes of Colombian and Jamaican #1 blacks were an admixture between Africans and Caucasians or South American Indians, while Jamaican #2 blacks were relatively homogeneous and appeared to conserve African lineages. The major five-locus HLA haplotypes were not shared among Colombian, Jamaican #1 and Jamaican #2 blacks. These results indicated that the black populations of Colombia and Jamaica were originated from African blacks and admixed variably with Caucasians and South American Indians to make genetic subpopulations in Colombia and Jamaica.     

High heterogeneity of apolipoprotein E gene frequencies in South American Indians

The apolipoprotein E (APOE) polymorphism was investigated in 186 individuals from six South American Indian tribes, and the results integrated with those previously presented for this ethnic group. The three APOE alleles commonly reported in other populations were also observed in South Amerindians with a highly heterogeneous distribution. As in other populations, APOE*3 was the most common allele (51-98%) followed by APOE*4 (2-47%). These two isoforms were identified in all tribes, but APOE*2 was observed among the Wai Wai (2%) and Mataco (4%) only. No previous indications of inter-ethnic admixture were observed among the Wai Wai, but the introduction of this allele among the Mataco through non-Indian sources cannot be excluded.     

HLA polymorphism in a Guarani‐Indian population from Paraguay and its usefulness for the Hispano‐Indian admixture study in Paraguay

In this study we investigated the human leucocyte antigen‐A (HLA‐A), ‐B and DRB1 polymorphism of Native American population of Paraguay, the Guarani Indians. We found that the HLA variability consisted of 5 HLA‐A, 7 HLA‐B and 6 HLA‐DRB1 groups of alleles and of several specific alleles ( B*1504, B*3505, B*3912, B*4004, B*5104, DRB1*0411, DRB1*1413) common in other Native American populations. The comparison of the HLA polymorphism of the Guaranis from Paraguay with the «Mestizos» of Paraguay and the Spaniards showed that the «Mestizos» of Paraguay are genetically very distant from the Guarani Indians of Paraguay but much more close to the Spaniards. This can be explained, at least in part, by the history of the country. Our results are of importance in transplantation, in particular in the search for an unrelated donor for a Paraguayan patient requiring hematopoietic stem cell transplantation.     

Genetics of apolipoprotein H (β 2 -glycoprotein I) polymorphism in India

Background : Human apolipoprotein H ( &#103 2 -glycoprotein I, apoH, protein; APOH, gene) is a single-chain glycoprotein that has been implicated in several metabolic pathways, including lipid metabolism, coagulation and production of antiphospholipid antibodies and many disease phenotypes. The structural, molecular and genetic bases of APOH have been studied in detail but population studies, especially from the Indian sub-continent, are limited. Objective : This study seeks to enlarge our understanding of APOH genetic diversity in human populations from different regions and social groups of India. Also, we examine the level and extent of genetic variation at this locus in world populations and its utility as a population genetic marker. Subjects and methods : Blood samples from 1381 unrelated and randomly selected individuals were screened for APOH genetic polymorphism. Eleven populations from North India (Brahmins, Banias, Jat Sikhs, Khatris, Scheduled Castes, Lobanas and Rajputs), West India (Brahmin and Patels) and Central India (Brahmins and Baiga tribe) were studied for APOH polymorphism using isoelectric focusing. Allele frequencies were calculated by the gene counting method. The results were statistically evaluated using chi-square statistics for regional and ethnic variation. Genetic distances were computed on Indian populations to determine the population affinities. Correspondence analysis was used to assess ethnic variation in world populations. Results : An interesting and wide genetic variation at this locus was observed in Indian populations. The frequency distribution of three observed alleles ranged from 0.034 to 0.091 for APOH*1, 0.852 to 0.917 for APOH*2 and 0.027 to 0.075 for APOH*3. The world's highest APOH*2 allele frequency was observed in the Patel (0.917) caste group from West India. Conclusions : Overall, the observed variation at this locus in Indian populations is comparable to many Caucasian populations. An analysis of world populations showed that APOH is a useful genetic marker for population and anthropological studies.     

Group‐specific component (GC) in curiaú and pacoval,two african‐derived brazilian populations

The group‐specific component (GC) system is of interest in anthropological genetic studies because the distribution of its subtypes distinguishes among major ethnic groups. The GC system was analyzed in Curiaú and Pacoval, two remnant Quilombo populations (African‐derived populations) from the Brazilian Amazon. There was no significant statistical difference in allelic frequencies between the two populations or between them and three other African‐derived Brazilian populations (Mimbó, Sítio Velho, and Gaucinha in Northeastern Brazil). These populations share similarities among themselves and with African populations (high frequencies of GC*1F and lower frequencies of GC*1S), which may reflect the influence of a high level of African contribution to their formation, but there is a clear difference between them and Europeans and South American Indians. It is suggested that the GC system is a useful marker for studying relationships between single populations and major ethnic groups, but does not discriminate between populations which share the same parental stock. Am. J. Hum. Biol. 13:718–720, 2001. © 2001 Wiley‐Liss, Inc.     

Differences in HLA class II alleles of isolated South American Indian populations from Brazil and Argentina

We have studied the HLA class II alleles in 277 South American Indians, which included Argentinian tribes from the Gran Chaco: Toba (n = 135), Toba-Pilaga (n = 19), Mataco-Wichi (n = 49), and Xavantes, a tribe from Central Brazil (n = 74). In the Brazilian tribe, only four DR groups were found: DRB1^*1602 (gf = 0.303), DRB1^*04 including DRB1^*0404 (gf = 0.070) and DRB1^*0407 (gf = 0.077), DRB1^*0802 fgf = 0.265), and DRB1^*1402 (gf = 0.303). The HLA class II allele frequencies were similar among the different Argentinian tribes, and 90% of DRB1 alleles belonged to three families: DRB1^*04 (including DRB1^*0403, DRB1^*0404, DRB1^*0407, DRB1^*0411, and DRB1^*0417), DRB1^*0802, and DRB1^*14 (including DRB1^*1402 and DRB1^*1406). At the DPB1 locus, we found only seven alleles, the most frequent being DPB1^*0402. Comparison of HLA class II alleles with those of North American Indians that we have previously studied shows that the frequency of some HLA class II alleles in Brazilian Xavantes resembles that of North American Indians more than that of the Argentinian Indian tribes. The allele DRB1^*0417 was found exclusively in this population.     

Subdivision of HL-A5 and Comparative Studies of the HL-A Polymorphism in South African Indians

The HL-A5 antigen has a higher frequency in the Indian population than in either the Caucasian or Bantu populations of South Africa. Ninety-five Asian Indians were tested by microcytotoxicity using 34 anti-HL-A5 and nine anti-W5 sera. The results confirm the heterogeneity of the HL-A5 antigen and show that it may be subdivided into at least four parts. The Indian population of South Africa is here subdivided into four groups. The HL-A antigen frequencies in each group are compared, and haplotype frequencies and gametic associations (delta values) have been calculated. The genetic distances (f) between these groups and between Indians. Caucasians and Bantu also are calculated. The results may indicate a differential selection with respect to the HL-A polymorphism.