Binary and microsatellite polymorphisms of the Y‐chromosome in the Mbenzele pygmies from the Central African Republic

This study analyzes the variation of six binary polymorphisms and six microsatellites in the Mbenzele Pygmies from the Central African Republic. Five different haplogroups (B2b, E(xE3a), E3a, P and BR(xB2b,DE,P)) were observed, with frequencies ranging from 0.022 (haplogroup P) to 0.609 (haplogroup E3a). A comparison of haplogroup frequencies indicates a close genetic affinity between the Mbenzele and the Biaka Pygmies, a finding consistent with the common origin and the geographical proximity of the two populations. The haplogroups P, BR(xB2b,DE,P) and E(xE3a), which are rare in sub‐Saharan Africa but common in western Eurasia, were observed with frequencies ranging from 0.022 (haplogroup P) to 0.087 (haplogroup E(xE3a)). Thirty different microsatellite haplotypes were detected, with frequencies ranging from 0.022 to 0.152. The Mbenzele share the highest percent of microsatellite haplotypes with the Biaka Pygmies. Five out seven haplotypes which are shared by the Mbenzele and Biaka Pygmies belong to haplogroup E3a, which suggests that they are of Bantu origin. The plot based on F_st genetic distances calculated using microsatellite data provides a picture of population relationships which is in part congruent and in part complementary to that obtained using haplogroup frequencies. Finally, the Mbenzele and Biaka Pygmies were found to be markedly more genetically similar using Y‐chromosomal than autosomal microsatellites. We suggest that this could be due to the higher phylogenetic stability of Y‐chromosome and to the effect of the male‐biased gene flow during the Bantu expansion. Am. J. Hum. Biol. 16:57–67, 2004. © 2003 Wiley‐Liss, Inc.     

HLA class I variation in the West African Pygmies and their genetic relationship with other African populations

We have studied the polymorphism of HLA class I in two West African Pygmy populations, namely, the Bakola from Cameroon and the Mbenzele from the Central African Republic. A unique number of HLA alleles and haplotypes showed specific patterns of these populations. In this study, we identify two alleles (B*37, B*41) and three haplotypes (A*30-B*37, A*66-B*41 and A*68-B*58) that appear to be 'private' or typical of Western Pygmies. These data reflect similarities with the AKA Pygmies from the Central African Republic. On the other hand, we failed to identify alleles that are found at high frequencies among other sub-Saharan populations (B*42, B*51). Allelic and haplotypic frequency distributions show differences between the two Pygmy groups, e.g. B*35 was very common in the Mbenzele but has been found to be absent in the Bakola. In contrast, B*53, which is found in the Bakola, has been found to be rare in the Mbenzele Pygmies. In order to analyse the genetic relationships of the Bakola and Mbenzele Pygmies with other sub-Saharan populations, HLA gene frequencies were subjected to the Neighbour-Joining tree analysis. The Mbenzele, Bakola and AKA were found to be relatively close to each other and isolated from other sub-African populations. However, both the genetic distances and the within-group variation suggests that the Bakola are more admixed with Bantu farmers than Mbenzele.     

Genetic variation at the ApoB 3′ HVR minisatellite locus in the Mbenzele Pygmies from the Central African Republic

This study analyzes the polymorphic minisatellite ApoB 3′ HVR in the Mbenzele Pygmies from the Central African Republic. A total of 14 alleles was observed, with frequencies ranging from 0.020 (19, 21, 27, and 45 repeat unit alleles) to 0.210 (37 repeat unit allele). Departure from Hardy-Weinberg equilibrium was not statistically significant. The estimated heterozygosity was 0.874 ± 0.016. Taking data from the literature into consideration, the results support the hypothesis that the Africans are different from non-Africans due to greater ApoB 3′ HVR genetic diversity and a unimodal profile of ApoB 3′ HVR allele frequency distribution. Interpopulational relationships were also analyzed using an F_ST based genetic distance. The results highlight the similarity between the Mbenzele Pygmies and Bantu-speaking groups (Ewondo and Zulu), and the divergence between the Mbenzele and San, the two groups which are often considered to be the most direct descendants of proto-Africans. Am. J. Hum. Biol. 12:588–592, 2000. © 2000 Wiley-Liss, Inc.     

Genetic admixture in three mexican mestizo populations based on D1S80 and HLA‐DQA1 Loci

This study compares genetic polymorphisms at the D1S80 and HLA‐DQA1 loci in three Mexican Mestizo populations from three large states (Nuevo León, Jalisco, and the Federal District). Allele frequency distributions are relatively homogenous in the three samples; only the Federal District population shows minor differences of the HLA‐DQA1 allele frequencies compared with the other two. In terms of genetic composition, these Mestizo populations show evidence of admixture with predominantly Spanish‐European (50–60%) and Amerindian (37–49%) contributions; the African contribution (1–3%) is minor. Together with the observation that in Nuevo León, the admixture estimates based on D1S80 and HLA‐DQA1, are virtually the same as those reported earlier from blood group loci, suggests that DNA markers, such as D1S80 and HLA‐DQA1 are useful for examining genetic homogeneity/heterogeneity across Mestizo populations of Mexico. The inverse relationship of the proportion of gene diversity due to population differences (G_st) to within population gene diversity (H_s) is also consistent with theoretical predictions, supporting the use of these markers for population genetics studies. Am. J. Hum. Biol. 14:257–263, 2002. © 2002 Wiley‐Liss, Inc.     

Exploration and mating range in African Pygmies

The distributions of exploration range and of mating range were studied among Aka Pygmies of the Central African Republic. Exploration range is defined and methods of estimation for single individuals suggested. A simple exponential distribution is found for individual Aka Pygmies, with variation of exploration range (the parameter defining mobility) with sex, age and ethnic affiliation. Distribution of distances from birthplace and place of residence are compared and show modest differences. The frequency of visits to a given place has also been studied.
The average distance between birthplaces of mates is very similar to the mean exploration range. Correlations between individual exploration and mating ranges suggest that it is the male who may be choosing a marriage partner among Pygmies. A theory by Boyce, Küchemann & Harrison (1967) on the relations between 'neighbourhood knowledge' and mating distance is inapplicable because of its reliance on the Pareto distribution, which does not apply in the present case, and of other unnecessary assumptions, but the general priciple of a close relationship between exploratory activity and mating distance seems valid, at least in the present case. Suggestions are made for causes of the difference between the present distributions and those with other shapes observed in less primitive economies.     

Population structure of the rural communities on the island of Krk (Croatia): A comparison of genetic,cultural, and geographic data

The population structure of seven rural communities from the island of Krk (Croatia) was studied on the basis of its genetic constitution and genetic structure, and different sets of biological (genetic), biocultural (migration), cultural (linguistic), and geographic data. Genetic constitution was estimated from the allelic frequencies of nine tetranucleotide STR loci, three HLA class I loci, five HLA class II loci, and five red blood cell enzyme and serum protein loci. Genetic structure was based on coefficients of genetic diversity G_ST and genetic kinship R_ST. Population structure was assessed by the structure of mutual relationships among biological, biocultural, cultural, and geographic matrices through Mantel's test, or by relationships among biological, biocultural, cultural measures of distance and/or similarity, and geographic distance with regression analysis of the “isolation by distance” model. One group of genetic markers (red blood enzymes, serum proteins, and HLA polymorphisms) reflects heterogeneity of the rural communities (a reflection of important historical processes and migration patterns), and a second group of genetic markers (STR polymorphisms) reflects the currently observed genetic homogeneity of the rural population. The positive correlations between the matrices of genetic (HLA) and linguistic distances indicate their possible co-evolution under conditions of genetic isolation (low gene flow). Furthermore, the negative correlations between the matrices of genetic (STR) distances and the migration kinship of the second and the third cohort indicate temporal coincidence between genetic constitution and structure assessed from STRs and migration patterns in the period between 1892 and 1940. Finally, the positive correlations between the matrices of genetic (STR) and geographic distances indicate isolation by distance. Am. J. Hum. Biol. 12:509–525, 2000. © 2000 Wiley-Liss, Inc.     

Genomic ancestry of a sample population from the state of São Paulo,Brazil

Allelic frequencies of eight autosomal short‐tandem repeat (STR) loci (TH01, TPOx, CSF1PO, vWA, FES/FPS, F13A1, F13B, and CD4) were determined in 400 individuals born in the State of São Paulo. No significant deviations from Hardy‐Weinberg equilibrium were found in any loci analyzed. The Unweighted Pair‐Group Method with Arithmetic Mean (UPGMA) tree constructed based on genetic distances revealed that the present population was grouped with Europeans, and separated from African and Amerindian populations. Estimates of admixture components based on the gene identity method revealed 79% European, 14% African, and 7% Amerindian contributions to this Brazilian population sample. Am. J. Hum. Biol. 18:702–705, 2006. © 2006 Wiley‐Liss, Inc.     

Genetic variability in the Guahibo population from venezuela

Four communities from Guahibo of Venezuela were analyzed for the genetic variants of nine erythrocyte enzymes and five serum proteins. Of the 14 loci determined, four were monomorphic. Significant frequency differentiation among communities, was present for ESD and TF markers. In general, Guahibo allele frequencies are in the variation ranges described for South American groups. The analysis indicates a relatively higher affinity of Guahibos with other Venezuelan groups within an irregular pattern of genetic distances that are likely related to the complex demographic history of the South American groups. Genetic diversity estimates reveal a moderate degree of genetic structure between the four Guahibo communities. This intra‐tribal variability in Guahibo appears to be lower than in Venezuelan Piaroa but higher than in other Amerindians and could be attributed to a combined effect of low population size and relative isolation of communities. At a continental level, the distribution of genetic diversity is consistent with preferential population movements along the eastern and western coastal areas. Am. J. Hum. Biol. 14:21–28, 2002. © 2002 Wiley‐Liss, Inc.     

HLA class II polymorphism in Aka Pygmies and Bantu Congolese and a reassessment of HLA-DRB1 African diversity

HLA-DRB1, -DQB1 and -DPB1 polymorphisms were investigated in two African populations, the Basse Lobaye Aka Pygmies of the Central African Republic, and a Bantu-speaking group from the Democratic Republic of Congo Kinshasa. Allelic and haplotypic frequency distributions reveal marked differences between the two populations in spite of their geographical proximity: the Aka exhibit high frequencies for several alleles, especially at the DPB1 locus (0.695 for DPB1*0402), probably due to rapid genetic drift, while the Bantu distributions are more even. Genetic distances computed from DRB1 allelic frequencies among 21 populations from North and sub-Saharan Africa were applied to a multidimensional scaling analysis. African populations genetic structure is significantly shaped by linguistic differentiation, as confirmed by an analysis of molecular variance. However, selective neutrality tests indicate that many African populations exhibit an excess of heterozygotes for DRB1, which is likely to explain the genetic similarity observed between some North African and Bantu populations. Overall, this study shows that natural selection must be taken into account when interpreting the patterns of HLA diversity, but that this effect is probably minor in relation to the stochastic events of human population differentiations.     

Population structure and genetic differentiation among the substructured Vysya caste population in comparison to the other populations of Andhra Pradesh,India

Objectives : The present paper focuses on the study of the patterns of genetic microdifferentiation among one of the substructured caste populations of Andhra Pradesh, namely Vysya, with reference to 17 other Telugu speaking populations from the same region of India. Subjects and methods : A total of 302 individuals from the three Vysya subgroups (101 of Arya Vysya, 100 from Kalinga Vysya and 101 from Thrivarnika) were typed in 17 blood groups and protein polymorphisms. Nei's gene diversity analysis, as well as neighbour-joining tree and UPGMA cluster diagrams, derived from standard genetic distances, R-matrix analysis and a regression model for investigating the patterns of external gene flow and genetic drift due to isolation under the island model, were done at two levels: (1) considering only the three Vysya populations and (2) considering common loci among 20 populations of Andhra Pradesh. Results : Seven of the 17 systems investigated were found to be monomorphic among all the three Vysya groups. The UPGMA tree and bidimensional scaling of the D 2 distances derived from R-matrix analysis show a very distinct cluster of Vysya populations. Application of the model of regression of average heterozygosity versus the distance of populations from the centroid shows the three Vysya populations placed as clear outliers above the theoretical regression line. Conclusions : Different approaches employed in this study give support to the hypothesis of different origin and/or demographic story for the three Vysya groups compared with other populations of Andhra Pradesh.     

Genetic profile based upon 15 microsatellites of four caste groups of the eastern Indian state,Bihar

Background: The formation of caste groups among the Hindu community and the practice of endogamy exert a great impact on the genetic structure and diversity of the Indian population. Allele frequency data of 15 microsatellite loci clearly portray the genetic diversity and relatedness among four socio-culturally advanced caste groups: Brahmin, Bhumihar, Rajput and Kayasth of Caucasoid ethnicity of Bihar. Aim: The study seeks to understand the impact of the man-made caste system on the genetic profile of the four major caste groups of Bihar. Methods and procedure: Computation of average heterozygosity, most frequent allele, allele diversity and coefficient of gene differentiation (Gst), along with genetic distance (D_A) and principal coordinate analysis were performed to assess intra-population and inter-population diversity. Main outcomes and results: The average Gst value for all the loci was 0.012 ± 0.0033, and the level of average heterozygosity was ?75.5%, indicating genetic similarity and intra-population diversity. Genetic distance (D_A) values and the phylogenetic tree along with other higher caste groups of India indicate the relative distance between them. Conclusion: The present study clearly depicts the genetic profile of these caste groups, their inherent closeness in the past, and the impact of the imposed caste system that later restricted the gene flow. The study highlights the status of Bhumihar and Kayasth in the Hindu caste system. The former was found clustering with the Brahmin group (as expected, since Bhumihar is known to be a subclass of Brahmin), whereas the distance between the Brahmin and Kayasth caste groups was found to be large. North-eastern Indian Mongoloids form a separate cluster.     

The distribution of linkage disequilibrium over anonymous genome regions

Linkage disequilibrIum (LD), the association of alleles at differentloci, is a powerful tool for genetic mapping and for investigating,at the population level, processes such as recombination, selection,mutation and admixture. Little is known about the distributionof LD across mammalian genomes. Therefore, a survey was undertaken,using microsatellite loci, to evaluate the distribution of LDover several regions of human chromosome 4. Radiation hybrid(RH) and linkage maps provided information on physical and geneticdistances between these lad. A Finnish popu lation sample wasgenotyped using 32 mlcrosateilite lad, and partial marker haplotypeswere determined. Assessment of LD was performed, between allpairs of iocl, using the Fisher's exact test. LD was detectedbetween several loci that were separated by more than 1 Mb or1 cM. Detection of LD was strongly associated with small physicaldistance; its relation to genetic distance was more equivocal.This result may support the hypothesis that linkage maps arerelatively inaccurate over small distances. Our results suggestthat LD is widely distributed in anonymous regions of the humangenome and its use may allow more accurate measurement of smallgenetic distances than does standard linkage analysis. Alternativeexplanations are considered for comparisons in which LD is notdetected between tightly linked loci.     

Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci

The allelic and haplotypic diversity of the HLA-A, HLA-B, and HLA-C loci was investigated in 852 subjects from five sub-Saharan populations from Kenya (Nandi and Luo), Mali (Dogon), Uganda, and Zambia. Distributions of genotypes at all loci and in all populations fit Hardy-Weinberg equilibrium expectations. There was not a single allele predominant at any of the loci in these populations, with the exception of A*3002 [allele frequency (AF) = 0.233] in Zambians and Cw*1601 (AF = 0.283) in Malians. This distribution was consistent with balancing selection for all class I loci in all populations, which was evidenced by the homozygosity F statistic that was less than that expected under neutrality. Only in the A locus in Zambians and the C locus in Malians, the AF distribution was very close to neutrality expectations. There were six instances in which there were significant deviations of allele distributions from neutrality in the direction of balancing selection. All allelic lineages from each of the class I loci were found in all the African populations. Several alleles of these loci have intermediate frequencies (AF = 0.020-0.150) and seem to appear only in the African populations. Most of these alleles are widely distributed in the African continent and their origin may predate the separation of linguistic groups. In contrast to native American and other populations, the African populations do not seem to show extensive allelic diversification within lineages, with the exception of the groups of alleles A*02, A*30, B*57, and B*58. The alleles of human leukocyte antigen (HLA)-B are in strong linkage disequilibrium (LD) with alleles of the C locus, and the sets of B/C haplotypes are found in several populations. The associations between A alleles with C-blocks are weaker, and only a few A/B/C haplotypes (A*0201-B*4501-Cw*1601; A*2301-B*1503-Cw*0202; A*7401-B* 1503-Cw*0202; A*2902-B*4201-Cw*1701; A*3001-B*4201-Cw*1701; and A*3601-B*5301-Cw*0401) are found in multiple populations with intermediate frequencies [haplotype frequency (HF) = 0.010-0.100]. The strength of the LD associations between alleles of HLA-A and HLA-B loci and those of HLA-B and HLA-C loci was on average of the same or higher magnitude as those observed in other non-African populations for the same pairs of loci. Comparison of the genetic distances measured by the distribution of alleles at the HLA class I loci in the sub-Saharan populations included in this and other studies indicate that the Luo population from western Kenya has the closest distance with virtually all sub-Saharan population so far studied for HLA-A, a finding consistent with the putative origin of modern humans in East Africa. In all African populations, the genetic distances between each other are greater than those observed between European populations. The remarkable current allelic and haplotypic diversity in the HLA system as well as their variable distribution in different sub-Saharan populations is probably the result of evolutionary forces and environments that have acted on each individual population or in their ancestors. In this regard, the genetic diversity of the HLA system in African populations poses practical challenges for the design of T-cell vaccines and for the transplantation medical community to find HLA-matched unrelated donors for patients in need of an allogeneic transplant.     

A View of Modern Human Origins from Y Chromosome Microsatellite Variation

The idea that all modern humans share a recent (within the last 150, 000 years) African origin has been proposed and supported on the basis of three observations. Most genetic loci examined to date have (1) shown greater diversity in African populations than in others, (2) placed the first branch between African and all non-African populations in phylogenetic trees, and (3) indicated recent dates for either the molecular coalescence (with the exception of some autosomal and X-chromosomal loci) or for the time of separation between African and non-African populations. We analyze variation at 10 Y chromosome microsatellite loci that were typed in 506 males representing 49 populations and every inhabited continent and find significantly greater Y chromosome diversity in Africa than elsewhere, find the first branch in phylogenetic trees of the continental populations to fall between African and all non-African populations, and date this branching with the (deltamu)2 distance measure to 5800-17,400 or 12,800-36,800 years BP depending on the mutation rate used. The magnitude of the excess Y chromosome diversity in African populations appears to result from a greater antiquity of African populations rather than a greater long-term effective population size. These observations are most consistent with a recent African origin for all modern humans.     

Genetic polymorphisms,forensic efficiency,and phylogenetic analysis of 15 autosomal STR loci in the Uygur population of Ili Kazakh Autonomous Prefecture,Northwestern China

The genetic polymorphisms of 15 autosomal short tandem repeat (STR) loci were analyzed in 449 individuals of the Uygur population from Ili Kazakh Autonomous Prefecture, Northwestern China. Phylogenetic analysis was performed among the Ili Uygur population and other relevant populations. The neighbor‐joining tree and multidimensional scaling plot were generated based on the Nei's standard genetic distance. We found a total of 173 alleles with corresponding frequencies ranging from 0.5022 to 0.0011. The combined powers of discrimination and exclusion for the 15 autosomal STR loci were 0.99999999985 and 0.99999880065, respectively. Population comparisons indicated that the Ili Uygur population had a relatively close genetic relationship with the Uygur populations from other regions of China. The pairwise genetic distance and P‐values between Ili Uygur and 10 published populations showed that no statistically significant differences existed between the Ili Uygur population and the Kashi, Kashgar, and Kotan Uygur. Therefore, the Ili Uygur population has its own unique Uygur genetic characteristics that were different from the other ethnic populations of China.     

Genetic structure and admixture in urban populations of the Argentine North-West

BACKGROUND: From the ethnic point of view, the Argentine North-West (ANW) constitutes one of the most noticeable areas in the country due to the cultural peculiarities that integrate it to the Andean world and the ethno-historical and demographic characteristics of how it became populated. AIM: The study analysed the genetic structure and diversity of the ANW urban populations, and the contribution of parental populations to its genetic pool.Subjects and methods: Previously reported data on allele frequencies of HLA-A and HLA-B loci of 1293 individuals from Jujuy, Salta, Tucumán, Santiago del Estero, Catamarca and La Rioja were used. Our estimates include: (a) genetic intra-population diversity; (b) genetic distances between populations; (c) linkage disequilibrium (LD); (d) admixture rates and genetic distances with respect to three parental populations (European, American Indian and African). RESULTS: Low intra-population genetic differentiation and low genetic distances between populations were found. Differential LD distribution varied according to province, with 60% variance due to intra-population differences. The Spanish contribution (50%) predominated in ANW, followed by the American Indian (40%) and African (10%) contributions, and a marked inter-population heterogeneity of genetic admixture rates was observed. The shortest genetic distance was found in the American Indian parental population, and the longest in the African parental population. CONCLUSION: Five hundred years after the Spanish conquest, urban populations at ANW that have probably been subject to the same evolutionary forces present low genetic diversity and a similar genetic structure. Genetic distances and admixture percentages observed agree with census and ethno-historical data on settlement in the region.     

Population structure and genetic differentiation among the substructured Vysya caste population in comparison to the other populations of Andhra Pradesh,India

OBJECTIVES: The present paper focuses on the study of the patterns of genetic microdifferentiation among one of the substructured caste populations of Andhra Pradesh, namely Vysya, with reference to 17 other Telugu speaking populations from the same region of India. SUBJECTS AND METHODS: A total of 302 individuals from the three Vysya subgroups (101 of Arya Vysya, 100 from Kalinga Vysya and 101 from Thrivarnika) were typed in 17 blood groups and protein polymorphisms. Nei's gene diversity analysis, as well as neighbour-joining tree and UPGMA cluster diagrams, derived from standard genetic distances, R-matrix analysis and a regression model for investigating the patterns of external gene flow and genetic drift due to isolation under the island model, were done at two levels: (1) considering only the three Vysya populations and (2) considering common loci among 20 populations of Andhra Pradesh. RESULTS: Seven of the 17 systems investigated were found to be monomorphic among all the three Vysya groups. The UPGMA tree and bidimensional scaling of the D(2) distances derived from R-matrix analysis show a very distinct cluster of Vysya populations. Application of the model of regression of average heterozygosity versus the distance of populations from the centroid shows the three Vysya populations placed as clear outliers above the theoretical regression line. CONCLUSIONS: Different approaches employed in this study give support to the hypothesis of different origin and/or demographic story for the three Vysya groups compared with other populations of Andhra Pradesh.     

Dissimilarities in the process of formation of curiaú, a semi‐isolated Afro‐Brazilian population of the Amazon region

The genetic consequences of the social policy of the past in relation to the formation of Afro‐Brazilian societies are interesting and have been studied at various biological levels (classical polymorphisms and the mitochondrial and nuclear levels. These allow the estimation of the contribution of African genes and the participation of other ethnic groups in the formation of these communities. With this objective, uniparental systems of exclusively maternal (mtDNA) or paternal (Y‐DNA) inheritance in the Curiaú community were analyzed. The results demonstrate a differential contribution of the maternal and paternal genetic systems. Thirty‐three sequences were identified by mtDNA analysis; 53% showing an African and 47% an Amerindian origin. For the paternal system, 57% were of African, 37% of European, and 6% of Amerindian origin. Am. J. Hum. Biol. 14:440–447, 2002. © 2002 Wiley‐Liss, Inc.     

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.     

Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations.

The HLA system is the most polymorphic of all human genetic systems. The frequency of HLA class I alleles and their linkage disequilibrium patterns differ significantly among human populations as shown in studies using serologic methods. Many DNA-defined alleles with identical serotypes may have variable frequencies in different populations. We typed HLA-A, B, and C loci at the allele level by PCR-based methods in 1,296 unrelated subjects from five major outbred groups living in the U.S.A (African, AFAM; Caucasians, CAU; Asian, ORI; Hispanic, HIS, and North American Natives, NAI). We detected 46, 100 and 32 HLA-A, B, and C alleles, respectively. ORI and HIS presented more alleles at each of these loci. There was lack of correlation between the levels of heterozygosity and the number of alleles detected in each population. In AFAM, heterozygosity (>90%) is maximized at all class I loci. HLA-A had the lowest heterozygosity in all populations but CAU. Tight LD was observed between HLA-B and C alleles. AFAM had weaker or nonexistent associations between alleles of HLA-A and B than other populations. Analysis of the genetic distances between these and other populations showed a close relationship between specific US populations and a population from their original continents. ORI exhibited the largest genetic distance with all the other U.S. groups and were closer to NAI. Evidence of admixture with CAU was observed for AFAM and HIS. HIS also had significant frequencies of AFAM and Mexican Indian alleles. Differences in both LD and heterozygosity levels suggest distinct evolutionary histories of the HLA loci in the geographical regions from where the U.S. populations originated.