Mexican American ancestry-informative markers: examination of population structure and marker characteristics in European Americans, Mexican Americans, Amerindians and Asians

Markers with large differences in allele frequencies between ethnicities provide ancestry information that can be applied to genetic studies. We identified over 100 biallelic ancestry informative markers (AIMs) with large allele frequency differences between European Americans (EA) and Pima Amerindians from laboratory and database screens. For 35 of these markers, Mayan, Yavapai and Quechuan Amerindians were genotyped and compared with EA and Pima allele frequencies. Markers with large allele frequency differences between EA and one Amerindian tribe showed only small differences between the Amerindian tribes. Examination of structure in individuals demonstrated a clear separation of subjects of European from those of Amerindian ancestry, and similarity between individuals from disparate Amerindian populations. The AIMs demonstrated the variation in ancestral composition of individual Mexican Americans, providing evidence of applicability in admixture mapping and in controlling for structure in association tests. In addition, a high percentage of single-nucleotide polymorphisms (SNPs) selected on the basis of large frequency differences between EA and Asian populations had large allele frequency differences between EA and Amerindians, suggesting an efficient method for greatly expanding AIMs for use in admixture mapping/structure analysis in Mexican Americans. Together, these data provide additional support for the practical application of admixture mapping in the Mexican American population.Electronic Supplementary Material Supplementary material is available in the online version of this article at     

Strong Selection at MHC in Mexicans since Admixture

Mexicans are a recent admixture of Amerindians, Europeans, and Africans. We performed local ancestry analysis of Mexican samples from two genome-wide association studies obtained from dbGaP, and discovered that at the MHC region Mexicans have excessive African ancestral alleles compared to the rest of the genome, which is the hallmark of recent selection for admixed samples. The estimated selection coefficients are 0.05 and 0.07 for two datasets, which put our finding among the strongest known selections observed in humans, namely, lactase selection in northern Europeans and sickle-cell trait in Africans. Using inaccurate Amerindian training samples was a major concern for the credibility of previously reported selection signals in Latinos. Taking advantage of the flexibility of our statistical model, we devised a model fitting technique that can learn Amerindian ancestral haplotype from the admixed samples, which allows us to infer local ancestries for Mexicans using only European and African training samples. The strong selection signal at the MHC remains without Amerindian training samples. Finally, we note that medical history studies suggest such a strong selection at MHC is plausible in Mexicans.     

Exploring Population Admixture Dynamics via Empirical and Simulated Genome-wide Distribution of Ancestral Chromosomal Segments

The processes of genetic admixture determine the haplotype structure and linkage disequilibrium patterns of the admixed population, which is important for medical and evolutionary studies. However, most previous studies do not consider the inherent complexity of admixture processes. Here we proposed two approaches to explore population admixture dynamics, and we demonstrated, by analyzing genome-wide empirical and simulated data, that the approach based on the distribution of chromosomal segments of distinct ancestry (CSDAs) was more powerful than that based on the distribution of individual ancestry proportions. Analysis of 1,890 African Americans showed that a continuous gene flow model, in which the African American population continuously received gene flow from European populations over about 14 generations, best explained the admixture dynamics of African Americans among several putative models. Interestingly, we observed that some African Americans had much more European ancestry than the simulated samples, indicating substructures of local ancestries in African Americans that could have been caused by individuals from some particular lineages having repeatedly admixed with people of European ancestry. In contrast, the admixture dynamics of Mexicans could be explained by a gradual admixture model in which the Mexican population continuously received gene flow from both European and Amerindian populations over about 24 generations. Our results also indicated that recent gene flows from Sub-Saharan Africans have contributed to the gene pool of Middle Eastern populations such as Mozabite, Bedouin, and Palestinian. In summary, this study not only provides approaches to explore population admixture dynamics, but also advances our understanding on population history of African Americans, Mexicans, and Middle Eastern populations.     

Ancestral components of admixed genomes in a Mexican cohort

For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study "virtual genomes" of admixed individuals. We apply this approach to a cohort of 492 parent-offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations-Africa, Europe, and America-vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10-15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people.     

Pre‐Hispanic Mesoamerican demography approximates the present‐day ancestry of Mestizos throughout the territory of Mexico

Over the last 500 years, admixture among Amerindians, Europeans, and Africans, principally, has come to shape the present‐day gene pool of Mexicans, particularly Mestizos, who represent about 93% of the total Mexican population. In this work, we analyze the genetic data of 13 combined DNA index system‐short tandem repeats (CODIS‐STRs) in 1,984 unrelated Mestizos representing 10 population samples from different regions of Mexico, namely North, West, Central, and Southeast. The analysis of molecular variance (AMOVA) test demonstrated low but significant differentiation among Mestizos from different regions (F_ST = 0.34%; P = 0.0000). Although the spatial analysis of molecular variance (SAMOVA) predicted clustering Mestizo populations into four well‐delimited groups, the main differentiation was observed between Northwest when compared with Central and Southeast regions. In addition, we included analysis of individuals of Amerindian (Purepechas), European (Huelva, Spain), and African (Fang) origin. Thus, STRUCTURE analysis was performed identifying three well‐differentiated ancestral populations (k = 3). STRUCTURE results and admixture estimations by means of LEADMIX software in Mestizo populations demonstrated genetic heterogeneity or asymmetric admixture throughout Mexico, displaying an increasing North‐to‐South gradient of Amerindian ancestry, and vice versa regarding the European component. Interestingly, this distribution of Amerindian ancestry roughly reflects pre‐Hispanic Native‐population density, particularly toward the Mesoamerican area. The forensic, epidemiological, and evolutionary implications of these findings are discussed herein. Am J Phys Anthropol 2009. © 2009 Wiley‐Liss, Inc.     

Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine

We and others have identified several hundred ancestry informative markers (AIMs) with large allele frequency differences between different major ancestral groups. For this study, a panel of 199 widely distributed AIMs was used to examine a diverse set of 796 DNA samples including self-identified European Americans, West Africans, East Asians, Amerindians, African Americans, Mexicans, Mexican Americans, Puerto Ricans and South Asians. Analysis using a Bayesian clustering algorithm (STRUCTURE) showed grouping of individuals with similar ethnic identity without any identifier other than the AIMs genotyping and showed admixture proportions that clearly distinguished different individuals of mixed ancestry. Additional analyses showed that, for the majority of samples, the predicted ethnic identity corresponded with the self-identified ethnicity at high probability (P > 0.99). Overall, the study demonstrates that AIMs can provide a useful adjunct to forensic medicine, pharmacogenomics and disease studies in which major ancestry or ethnic affiliation might be linked to specific outcomes.Electronic Supplementary Material Supplementary material is available for this article at     

Argentine population genetic structure: large variance in Amerindian contribution

Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies.     

The population genetics of Quechuas, the largest native South American group: autosomal sequences, SNPs, and microsatellites evidence high level of diversity

Elucidating the pattern of genetic diversity for non-European populations is necessary to make the benefits of human genetics research available to individuals from these groups. In the era of large human genomic initiatives, Native American populations have been neglected, in particular, the Quechua, the largest South Amerindian group settled along the Andes. We characterized the genetic diversity of a Quechua population in a global setting, using autosomal noncoding sequences (nine unlinked loci for a total of 16 kb), 351 unlinked SNPs and 678 microsatellites and tested predictions of the model of the evolution of Native Americans proposed by (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485-1496). European admixture is <5% and African ancestry is barely detectable in the studied population. The largest genetic distances were between African versus Quechua or Melanesian populations, which is concordant with the African origin of modern humans and the fact that South America was the last part of the world to be peopled. The diversity in the Quechua population is comparable with that of Eurasian populations, and the allele frequency spectrum based on resequencing data does not reflect a reduction in the proportion of rare alleles. Thus, the Quechua population is a large reservoir of common and rare genetic variants of South Amerindians. These results are consistent with and complement our evolutionary model of South Amerindians (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485-1496), proposed based on Y-chromosome data, which predicts high genomic diversity due to the high level of gene flow between Andean populations and their long-term effective population size.     

Amerindian (but not African or European) ancestry is significantly associated with diurnal preference within an admixed Brazilian population

Significant questions remain unanswered regarding the genetic versus environmental contributions to racial/ethnic differences in sleep and circadian rhythms. We addressed this question by investigating the association between diurnal preference, using the morningness–eveningness questionnaire (MEQ), and genetic ancestry within the Baependi Heart Study cohort, a highly admixed Brazilian population based in a rural town. Analysis was performed using measures of ancestry, using the Admixture program, and MEQ from 1,453 individuals. We found an association between the degree of Amerindian (but not European of African) ancestry and morningness, equating to 0.16 units for each additional percent of Amerindian ancestry, after adjustment for age, sex, education, and residential zone. To our knowledge, this is the first published report identifying an association between genetic ancestry and MEQ, and above all, the first one based on ancestral contributions within individuals living in the same community. This previously unknown ancestral dimension of diurnal preference suggests a stratification between racial/ethnic groups in an as yet unknown number of genetic polymorphisms.     

Genetic admixture, relatedness, and structure patterns among Mexican populations revealed by the Y-chromosome

Y-linked markers are suitable loci to analyze genetic diversity of human populations, offering knowledge of medical, forensic, and anthropological interest. In a population sample of 206 Mestizo males from western Mexico, we analyzed two binary loci (M3 and YAP) and six Y-STRs, adding to the analysis data of Mexican Mestizos and Amerindians, and relevant worldwide populations. The paternal ancestry estimated in western Mexican-Mestizos was mainly European (60-64%), followed by Amerindian (25-21%), and African ( approximately 15%). Significant genetic heterogeneity was established between Mestizos from western (Jalisco State) and northern Mexico (Chihuahua State) compared with Mexicans from the center of the Mexican Republic (Mexico City), this attributable to higher European ancestry in western and northern than in central and southeast populations, where higher Amerindian ancestry was inferred. This genetic structure has important implications for medical and forensic purposes. Two different Pre-Hispanic evolutionary processes were evident. In Mesoamerican region, populations presented higher migration rate (N(m) = 24.76), promoting genetic homogeneity. Conversely, isolated groups from the mountains and canyons of the Western and Northern Sierra Madre (Huichols and Tarahumaras, respectively) presented a lower migration rate (N(m) = 10.27) and stronger genetic differentiation processes (founder effect and/or genetic drift), constituting a Pre-Hispanic population substructure. Additionally, Tarahumaras presented a higher frequency of Y-chromosomes without Q3 that was explained by paternal European admixture (15%) and, more interestingly, by a distinctive Native-American ancestry. In Purepechas, a special admixture process involving preferential integration of non-Purepecha women in their communities could explain contrary genetic evidences (autosomal vs. Y-chromosome) for this tribe.     

Evaluating the X Chromosome-Specific Diversity of Colombian Populations Using Insertion/Deletion Polymorphisms

The European and African contribution to the pre-existing Native American background has influenced the complex genetic pool of Colombia. Because colonisation was not homogeneous in this country, current populations are, therefore, expected to have different proportions of Native American, European and African ancestral contributions. The aim of this work was to examine 11 urban admixed populations and a Native American group, called Pastos, for 32 X chromosome indel markers to expand the current knowledge concerning the genetic background of Colombia. The results revealed a highly diverse genetic background comprising all admixed populations, harbouring important X chromosome contributions from all continental source populations. In addition, Colombia is genetically sub-structured, with different proportions of European and African influxes depending on the regions. The samples from the North Pacific and Caribbean coasts have a high African ancestry, showing the highest levels of diversity. The sample from the South Andean region showed the lowest diversity and significantly higher proportion of Native American ancestry than the other samples from the North Pacific and Caribbean coasts, Central-West and Central-East Andean regions, and the Orinoquian region. The results of admixture analysis using X-chromosomal markers suggest that the high proportion of African ancestry in the North Pacific coast was primarily male driven. These men have joined to females with higher Native American and European ancestry (likely resulting from a classic colonial asymmetric mating type: European male x Amerindian female). This high proportion of male-mediated African contributions is atypical of colonial settings, suggesting that the admixture occurred during a period when African people were no longer enslaved. In the remaining regions, the African contribution was primarily female-mediated, whereas the European counterpart was primarily male driven and the Native American ancestry contribution was not gender biased.     

Analysis of paternal lineages in Brazilian and African populations

The present-day Brazilian population is a consequence of the admixture of various peoples of very different origins, namely, Amerindians, Europeans and Africans. The proportion of each genetic contribution is known to be very heterogeneous throughout the country. The aim of the present study was to compare the male lineages present in two distinct Brazilian populations, as well as to evaluate the African contribution to their male genetic substrate. Thus, two Brazilian population samples from Manaus (State of Amazon) and Ribeirão Preto (State of São Paulo) and three African samples from Guinea Bissau, Angola and Mozambique were typed for a set of nine Y chromosome specific STRs. The data were compared with those from African, Amerindian and European populations. By using Y-STR haplotype information, low genetic distances were found between the Manaus and Ribeirão Preto populations, as well as between these and others from Iberia. Likewise, no significant distances were observed between any of the African samples from Angola, Mozambique and Guinea Bissau. Highly significant Rst values were found between both Brazilian samples and all the African and Amerindian populations. The absence of a significant Sub-Saharan African male component resulting from the slave trade, and the low frequency in Amerindian ancestry Y-lineages in the Manaus and Ribeirão Preto population samples are in accordance with the accentuated gender asymmetry in admixture processes that has been systematically reported in colonial South American populations.     

Mitochondrial DNA studies show asymmetrical Amerindian admixture in Afro-Colombian and Mestizo populations

The origin of the African populations that arrived on the Colombian coasts at the time of the Spanish conquest and their subsequent settlement throughout the country and interaction with Amerindian and Spanish populations are features that can be analyzed through the study of mitochondrial DNA (mtDNA) markers. For this purpose, the present study investigates the admixture between these populations by analyzing the markers defining the main (A, B, C, D) and minor (X) founder haplogroups in Native Americans, the principal African haplogroup (L), and additional generic markers present in Caucasian (I, J, K, H, T, U, V, W) and minor African lineages (L3). As part of an interdisciplinary research program (the Expedición Humana, furthered by the Universidad Javeriana and directed by J.E. Bernal V.), 159 Afro-Colombians from five populations in which they are the majority and 91 urban Mestizos were studied. No Amerindian haplogroups (A-D, X) were detected in 81% of the Afro-Colombians. In those samples with Amerindian lineages (average 18.8%, with a range from 10% to 43%), haplogroup B predominated. When analyzed for the presence of African haplotypes, Afro-Colombians showed an overall frequency of 35.8% for haplogroup L mtDNAs, although with broad differences between populations. A few Afro-Colombian samples (1.9%) had mutations that have not been described before, and might therefore be considered as previously unsampled African variants or as new mutations arising in the American continent. Conversely, in Mestizos less than 22% of their mtDNAs belonged to non-Amerindian lineages, of which most were likely to be West Eurasian in origin. Haplogroup L mtDNAs were found in only one Mestizo (1.1%), indicating that, if present, admixture with African women would bring in other, rarer African lineages. On the other hand, in an accompanying paper (Keyeux et al. 2002) we have shown that Amerindians from Colombia have experienced little or no matrilineal admixture with Caucasians or Africans. Taken together, these results are evidence of different patterns of past ethnic admixture among Africans, Amerindians, and Spaniards in the geographic region now encompassing Colombia, which is also reflected in much of the region's cultural diversity.     

Cranial morphological variation among contemporary Mexicans: Regional trends,ancestral affinities,and genetic comparisons

Genetic research has documented geographical variation within Mexico that corresponds to trends in ancestry admixture from postcolonial times on. The purpose of this study is to determine whether craniometric variation among contemporary Mexicans is comparable to that reported in genetic studies. Standard osteometric measurements were taken on 82 male crania derived from forensic cases, with geographic origins of the specimens spanning over two‐thirds of Mexico's states. To study similarities in regional clustering patterns with genetic data, k‐means clustering analyses were performed, followed by chi‐square tests of association between cluster assignments and geographic region of origin. Normal mixtures analyses were performed, centered on three “ancestral” sample proxies to estimate classification probability to each ancestry. The results demonstrate that the cranial morphological sample data cluster similarly to the regional groupings inferred from the genetic data. Additionally, the results indicate a gradient trend in population structure for contemporary Mexicans, with the proportion of Amerindian ancestry increasing from North to South while, conversely, European ancestry proportion estimates increase from South to North. Furthermore, the probabilities for classification of African ancestry remained low across the regions, again reflecting the results for the genetic data. Cranial morphological variation is well aligned with the genetic data for describing broad trends among Mexican populations, as well as yielding comparable estimates of general ancestry affiliations that reflect Mexico's history of Spanish contact and colonialism. Am J Phys Anthropol 151:506–517, 2013. © 2013 Wiley Periodicals, Inc.     

Admixture in Mexico City: implications for admixture mapping of Type 2 diabetes genetic risk factors

Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275 controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and, West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions was 9.4 (95%, credible interval 3.8–22.6). This association of socioeconomic status with individual admixture proportion shows that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7–8.0), from which we can estimate that genome-wide admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus that contributes an ancestry risk ratio of at least 1.5.     

Afro-derived Amazonian populations: inferring continental ancestry and population substructure

A panel of Ancestry Informative Markers (AIMs) was used to identify population substructure and estimate individual and overall interethnic admixture in 294 individuals from seven African-derived communities of the Brazilian Amazon. A panel of 48 biallelic markers, representing the insertion (IN) or the deletion (DEL) of small DNA fragments, was employed for this purpose. Overall interethnic admixture estimates showed high miscegenation with other ethnic groups in all populations (between 46% and 64%). The proportion of ancestral genes varied significantly among individuals of the sample: the contribution of African genes varied between 12% and 75%; of European genes between 10% and 73%; and of Amerindians genes between 8% and 66%. The obtained data reveal a high contribution of Amerindian genes in these communities, unlike in other African-derived communities of the Northeast and the South of Brazil. In addition, the majority of the Amerindian contribution may result from the preferential inclusion of indigenous women in the African descent groups. High heterogeneity of the proportion of interethnic admixture among analyzed individuals was found when the proportion of ancestral genes of each individual of the sample was estimated. This heterogeneity is reflected in the fact that four populations can be considered as substructured and that the global African descent sample is possibly formed by two subpopulations.     

Admixture mapping provides evidence of association of the VNN1 gene with hypertension

Migration patterns in modern societies have created the opportunity to use population admixture as a strategy to identify susceptibility genes. To implement this strategy, we genotyped a highly informative ancestry marker panel of 2270 single nucleotide polymorphisms in a random population sample of African Americans (N = 1743), European Americans (N = 1000) and Mexican Americans (N = 581). We then examined the evidence for over-transmission of specific loci to cases from one of the two ancestral populations. Hypertension cases and controls were defined based on standard clinical criteria. Both case-only and case-control analyses were performed among African Americans. With the genome-wide markers we replicated the findings identified in our previous admixture mapping study on chromosomes 6 and 21 [1]. For case-control analysis we then genotyped 51 missense SNPs in 36 genes spaced across an 18.3 Mb region. Further analyses demonstrated that the missense SNP rs2272996 (or N131S) in the VNN1 gene was significantly associated with hypertension in African Americans and the association was replicated in Mexican Americans; a non-significant opposite association was observed in European Americans. This SNP also accounted for most of the evidence observed in the admixture analysis on chromosome 6. Despite these encouraging results, susceptibility loci for hypertension have been exceptionally difficult to localize and confirmation by independent studies will be necessary to establish these findings.     

Genome-wide Scan of 29,141 African Americans Finds No Evidence of Directional Selection since Admixture

The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study’s conclusion of selection in African Americans before admixture is also subject to doubt. This is because the F_ST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.     

FMR1 CGG repeat distribution and linked microsatellite-SNP haplotypes in normal Mexican Mestizo and indigenous populations

The (CGG)n repeat size distribution in the FMR1 gene was studied in healthy individuals: 80 X chromosomes of Mexican Mestizos from Mexico City and 33 X chromosomes of Mexican Amerindians from three indigenous communities (Purepechas, Nahuas, and Tzeltales), along with alleles and haplotypes defined by two microsatellite polymorphic markers (DXS548 and FRAXAC1) and two single nucleotide polymorphisms (FMRA and FMRB). Genetic frequencies of Mestizo and Amerindian subpopulations were statistically similar in almost all cases and thus were considered one population for comparisons with other populations. Sixteen (CGG)n alleles in the 17-38 size range were observed, and the most common were the 25 (38.0%), 26 (28.3%), and 24 (12.3%) repeat alleles. This pattern differs from most other populations reported, but a closer relation to Amerindian, European, and African populations was found, as expected from the historical admixture that gave rise to Mexican Mestizos. The results of the CA repeats analysis at DXS548-FRAXAC1 were restricted to nine haplotypes, of which haplotypes 7-4 (52.2%), 8-4 (23.8%), and 7-3 (11.5%) were predominant. The modal haplotype 7-4, instead of the nearly universal haplotype 7-3, had been reported exclusively in Eastern Asian populations. Likewise, only seven different FRAXAC1-FMRA-FMRB haplotypes were observed, including five novel haplotypes (3TA, 4TA, 3 - A, 4 - A, and 5 - A), compared with Caucasians. Of these, haplotypes - A (78.7%) and 3 - A (13.2%) were the most common in the Mexican population. These data suggest a singular but relatively low genetic diversity at FMR1 in the studied Mexican populations that may be related to the recent origin of Mestizos and the low admixture rate of Amerindians.     

Characterizing the admixed African ancestry of African Americans

Background

Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin.

Results

From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans.

Conclusions

These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry.