Individual estimates of European genetic admixture associated with lower body-mass index, plasma glucose, and prevalence of type 2 diabetes in Pima Indians

Individual genetic admixture estimates (IA) from European Americans (EAs) were computed in 7,996 members of the Gila River Indian Community (Arizona). Parental populations for the analysis were European Americans and full-heritage Pima Indians. A logistic regression was performed on 7,796 persons, to assess association of IA with type 2 diabetes. The odds ratio, comparing diabetes risk in full-heritage EAs with full-heritage Pima Indians, was 0.329 (95% confidence interval [CI] 0.225-0.482). Proportional-hazards analysis was performed on 5,482 persons who were nondiabetic at their first examination and 1,215 subjects who developed diabetes during the study. The hazard risk ratio for IA was 0.455 (95% CI 0.301-0.688). Nondiabetic persons had significantly more European IA. In nondiabetic Pimans, multivariate linear regressions of quantitative predictors of type 2 diabetes mellitus, including fasting plasma glucose, 2-h post-load plasma glucose, and body-mass index, showed significant inverse relations with IA when controlled for sex and age. These results illustrate the ongoing evolution of populations by the mechanism of gene flow and its effect on disease risk in the groups with admixture. When the two parental populations differ in disease prevalence, higher or lower risk is associated with admixture, depending on the origin of the admixed alleles and the relative magnitude of the disease prevalence in the parental populations. These data also illustrate the strong genetic components in type 2 diabetes and are consistent with one susceptibility locus common to obesity and diabetes.     

Admixture in Latin America: Geographic Structure,Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.     

Gm 3;5,13,14 and stated-admixture: independent estimates of admixture in American Indians.

Bernstein's formula for the estimation of the amount of admixture (m) in a hybrid population has been used frequently since its publication in 1931. While mathematically correct, it has not been shown to be correct in practice, because an independent estimate from a large sample has not been available. We have compared the estimate of m for Caucasian admixture derived by using Bernstein's formula with that estimated from stated-admixture (Sa) within a sample of 5,759 Native Americans. There was a linear relationship between the two variables (m = -.000275 + .714Sa; r = .976 for the grouped data, P = .0001).     

Population Differentiation of Southern Indian Male Lineages Correlates with Agricultural Expansions Predating the Caste System

Previous studies that pooled Indian populations from a wide variety of geographical locations, have obtained contradictory conclusions about the processes of the establishment of the Varna caste system and its genetic impact on the origins and demographic histories of Indian populations. To further investigate these questions we took advantage that both Y chromosome and caste designation are paternally inherited, and genotyped 1,680 Y chromosomes representing 12 tribal and 19 non-tribal (caste) endogamous populations from the predominantly Dravidian-speaking Tamil Nadu state in the southernmost part of India. Tribes and castes were both characterized by an overwhelming proportion of putatively Indian autochthonous Y-chromosomal haplogroups (H-M69, F-M89, R1a1-M17, L1-M27, R2-M124, and C5-M356; 81% combined) with a shared genetic heritage dating back to the late Pleistocene (10–30 Kya), suggesting that more recent Holocene migrations from western Eurasia contributed <20% of the male lineages. We found strong evidence for genetic structure, associated primarily with the current mode of subsistence. Coalescence analysis suggested that the social stratification was established 4–6 Kya and there was little admixture during the last 3 Kya, implying a minimal genetic impact of the Varna (caste) system from the historically-documented Brahmin migrations into the area. In contrast, the overall Y-chromosomal patterns, the time depth of population diversifications and the period of differentiation were best explained by the emergence of agricultural technology in South Asia. These results highlight the utility of detailed local genetic studies within India, without prior assumptions about the importance of Varna rank status for population grouping, to obtain new insights into the relative influences of past demographic events for the population structure of the whole of modern India.     

Evaluation of model fit of inferred admixture proportions

Model based methods for genetic clustering of individuals, such as those implemented in structure or ADMIXTURE, allow the user to infer individual ancestries and study population structure. The underlying model makes several assumptions about the demographic history that shaped the analysed genetic data. One assumption is that all individuals are a result of K homogeneous ancestral populations that are all well represented in the data, while another assumption is that no drift happened after the admixture event. The histories of many real world populations do not conform to that model, and in that case taking the inferred admixture proportions at face value might be misleading. We propose a method to evaluate the fit of admixture models based on estimating the correlation of the residual difference between the true genotypes and the genotypes predicted by the model. When the model assumptions are not violated, the residuals from a pair of individuals are not correlated. In the case of a bad fitting admixture model, individuals with similar demographic histories have a positive correlation of their residuals. Using simulated and real data, we show how the method is able to detect a bad fit of inferred admixture proportions due to using an insufficient number of clusters K or to demographic histories that deviate significantly from the admixture model assumptions, such as admixture from ghost populations, drift after admixture events and nondiscrete ancestral populations. We have implemented the method as an open source software that can be applied to both unphased genotypes and low depth sequencing data.     

Testing for ancient admixture between closely related populations

One enduring question in evolutionary biology is the extent of archaic admixture in the genomes of present-day populations. In this paper, we present a test for ancient admixture that exploits the asymmetry in the frequencies of the two nonconcordant gene trees in a three-population tree. This test was first applied to detect interbreeding between Neandertals and modern humans. We derive the analytic expectation of a test statistic, called the D statistic, which is sensitive to asymmetry under alternative demographic scenarios. We show that the D statistic is insensitive to some demographic assumptions such as ancestral population sizes and requires only the assumption that the ancestral populations were randomly mating. An important aspect of D statistics is that they can be used to detect archaic admixture even when no archaic sample is available. We explore the effect of sequencing error on the false-positive rate of the test for admixture, and we show how to estimate the proportion of archaic ancestry in the genomes of present-day populations. We also investigate a model of subdivision in ancestral populations that can result in D statistics that indicate recent admixture.     

Population Structure in the Roundtail Chub (Gila robusta Complex) of the Gila River Basin as Determined by Microsatellites: Evolutionary and Conservation Implications

Ten microsatellite loci were characterized for 34 locations from roundtail chub (Gila robusta complex) to better resolve patterns of genetic variation among local populations in the lower Colorado River basin. This group has had a complex taxonomic history and previous molecular analyses failed to identify species diagnostic molecular markers. Our results supported previous molecular studies based on allozymes and DNA sequences, which found that most genetic variance was explained by differences among local populations. Samples from most localities were so divergent species-level diagnostic markers were not found. Some geographic samples were discordant with current taxonomy due to admixture or misidentification; therefore, additional morphological studies are necessary. Differences in spatial genetic structure were consistent with differences in connectivity of stream habitats, with the typically mainstem species, G. robusta, exhibiting greater genetic connectedness within the Gila River drainage. No species exhibited strong isolation by distance over the entire stream network, but the two species typically found in headwaters, G. nigra and G. intermedia, exhibited greater than expected genetic similarity between geographically proximate populations, and usually clustered with individuals from the same geographic location and/or sub-basin. These results highlight the significance of microevolutionary processes and importance of maintaining local populations to maximize evolutionary potential for this complex. Augmentation stocking as a conservation management strategy should only occur under extreme circumstances, and potential source populations should be geographically proximate stocks of the same species, especially for the headwater forms.     

The Anthropology of Dust: Community Responses to Wind-Blown Sediments within the Middle Gila River Valley, Arizona

Dust in its myriad forms impacts human existence in arid environments; but dust is more than an environmental nuisance. It shapes and reshapes adaptive response and human ideology over the short and long term. In 2011, the Gila River Indian Community (GRIC), Arizona, U.S.A. sponsored a study of dust entrainment within the jurisdiction of its airshed. The study’s primary objectives were to determine the relationship between sediment sources and sinks in premodern contexts and how indigenous people have coped with eolian activity since intensive settlement of the Middle Gila River Valley began. Ethnographic and archaeological sources indicate that people respect winds and observe cultural procedures consistent with their origin and to reduce their ill effects. Geomorphic data also show stratigraphic correspondence between relic wash channels and adjacent terrace and sand sheet deposits demonstrating a long history of eolian activity derived from fluvial sources. Climatological data from PM10 “exceedance events” corroborate anthropological analyses indicating that extreme dust events are typically westerlies and occur during exceptionally dry periods. Eolian dust is part of the ambient ecosystem of the GRIC and should be viewed as such within the modern cultural and regulatory environment governing these emissions.     

Unequal contributions of male and female gene pools from parental populations in the African descendants of the city of Melo, Uruguay

In admixed populations, genetic contributions from males and females of specific parental populations can be of different proportions due to past directional mating during the process of genetic admixture. In this research paper, we provide evidence of such male- and female-specific differential admixture components of African, European, and American Indian origin in an admixed population from the city of Melo, in the northeastern region of Uruguay. From data on 11 autosomal markers from a sample of 41 individuals of mixed African descent, we estimated 47% African, 38% European, and 15% Amerindian contributions. In contrast, 6 mtDNA site-specific polymorphic markers showed that the mtDNA genome of these individuals was 52% African, 19% European, and 29% Amerindian, while from 3 Y-specific polymorphic sites, we estimated 30% African, 64% European, and 6% Amerindian contributions. We argue that this heterogeneity of admixture estimates results from disproportionate unions of European males with African and American Indian females from which this mixed African population was formed. Also, we argue that the asymmetry of the admixture estimates from the three sets of markers (autosomal, mtDNA, and Y-linked) is a result of the changes in the direction of mating during the history of the population. Implications of such evidence of directional mating are discussed, indicating the need of further demographic data for a quantitative assessment of the impact of directional mating on genetic structure of admixed populations.     

Using microsatellite and MHC variation to identify species, ESUs, and MUs in the endangered Sonoran topminnow

Highly variable loci can provide insight into the recognition of species, evolutionarily significant units (ESUs) and management units (MUs). In general, the ESU and MU categories are thought to be reflective of adaptive differences between them. Here we examine this premise by presenting a comprehensive examination of genetic variation for both microsatellite loci and a major histocompatibility complex (MHC) locus, thought to be of adaptive significance, in the endangered Sonoran topminnow. The extent of variation for the microsatellite loci and the MHC gene within the 13 populations of the Gila topminnow is highly correlated, suggesting that nonselective factors have played an important role in influencing variation within and between populations for the MHC locus. Therefore, using all of these loci, we found that the eight natural populations of the Gila topminnow fell into two different ESUs, one of which had four different MUs. The source of the Boyce Thompson sample, a population that was used extensively for restocking, appeared to be Monkey Spring. The source of the Watson Wash population also appeared to be Monkey Spring (or Boyce Thompson). The newly colonized Santa Cruz River population, which had the most genetic variation of any Gila topminnow population, appeared to descend primarily from Sonoita Creek populations. The Yaqui topminnow, presently considered another subspecies of the Sonoran topminnow, was very distinct for both microsatellite (only two of 25 alleles found in the Yaqui were in any of the Gila topminnow samples) and MHC alleles (nonoverlapping sets of alleles for the two groups). As a result, it appeared that the taxonomic status of the two subspecies should be re-evaluated and that full species status for Gila and Yaqui topminnows was appropriate. There was evidence for the importance of long-term selection at the MHC locus in the higher rate of nonsynonymous than synonymous substitution. In addition, there appeared to have been a duplication of the MHC locus that was present in most of the fish in six of the natural populations of the Gila topminnow.     

Association of African Genetic Admixture with Resting Metabolic Rate and Obesity Among Women

Objective: To investigate the role of genetic admixture in explaining phenotypic variation in obesity‐related traits in a sample of African‐American women (n = 145) and to determine significant associations between obesity traits and admixture genetic markers. Research Methods and Procedures: Associations between genetic admixture and BMI, resting metabolic rate, fat mass, fat‐free mass, and bone mineral density were tested using linear regression considering the estimation of admixture by 1) a maximum‐likelihood approach (MLA) and 2) a Bayesian analysis. Results: Both the conservative MLA and the Bayesian approach support an association between African genetic admixture and BMI. Evidence for the associations of African genetic admixture with fat mass and fat‐free mass was supported by the Bayesian analysis; the MLA supported an association with bone mineral density. When the individual ancestry informative markers that were used to estimate admixture were tested for associations with BMI, significant associations were identified in chromosomes 1, 11, and 12. Discussion: These results provide evidence supporting the application of admixture mapping methods to the identification of genes that result in higher levels of obesity among African‐American women. Further research is needed to replicate and further explore these findings.     

The population genetic effects of ancestry and admixture in a subdivided cattle breed

The genetic structure of the Dexter, a minority cattle breed with complex demographic history, was investigated using microsatellite markers and a range of statistical approaches designed to detect both admixture and genetic drift. Modern representatives of two putative ancestral populations, the Devon and Kerry, together with the different populations of the Dexter, which have experienced different demographic histories, were analysed. Breed units showed comparatively high levels of genetic variability ( H _E = 0.63–0.68); however, distinct genetic subgroups were detected within the Dexter, which could be attributed to known demographic events. Much lower diversity was identified in three small, isolated Dexter populations ( H _E = 0.52–0.55) and higher differentiation ( F _ST > 0.13) was found. For one of these populations, where strong selection has taken place, we also found evidence of a demographic bottleneck. Three methods for quantifying breed admixture were applied and substantial method-based variation in estimates for the genetic contribution of the two proposed ancestral populations for each subdivision of the Dexter was found. Results were consistent only in the case of a group consisting of selected Traditional Dexter animals, where the ancestor of the modern Kerry breed was also determined as the greater parental contributor to the Dexter. The inconsistency of estimation of admixture proportions between the methods highlights the potentially confounding role of genetic drift in shaping small population structure, and the consequences of accurately describing population histories from contemporary genetic data.     

Ancestral proportions and admixture dynamics in geographically defined African Americans living in South Carolina

We analyzed admixture in samples of six different African-American populations from South Carolina: Gullah-speaking Sea Islanders in coastal South Carolina, residents of four counties in the "Low Country" (Berkeley, Charleston, Colleton, and Dorchester), and persons living in the city of Columbia, located in central South Carolina. We used a battery of highly informative autosomal, mtDNA, and Y-chromosome markers. Two of the autosomal markers (FY and AT3) are linked and lie 22 cM apart on chromosome 1. The results of this study indicate, in accordance with previous historical, cultural, and anthropological evidence, a very low level of European admixture in the Gullah Sea Islanders (m = 3.5 +/- 0.9%). The proportion of European admixture is higher in the Low Country (m ranging between 9. 9 +/- 1.8% and 14.0 +/- 1.9%), and is highest in Columbia (m = 17.7 +/- 3.1%). A sex-biased European gene flow and a small Native American contribution to the African-American gene pool are also evident in these data. We studied the pattern of pairwise allelic associations between the FY locus and the nine other autosomal markers in our samples. In the combined sample from the Low Country (N = 548), a high level of linkage disequilibrium was observed between the linked markers, FY and AT3. Additionally, significant associations were also detected between FY and 4 of the 8 unlinked markers, suggesting the existence of significant genetic structure in this population. A continuous gene flow model of admixture could explain the observed pattern of genetic structure. A test conditioning on the overall admixture of each individual showed association of ancestry between the two linked markers (FY and AT3), but not between any of the unlinked markers, as theory predicts. Thus, even in the presence of genetic structure due to continuous gene flow or some other factor, it is possible to differentiate associations due to linkage from spurious associations due to genetic structure.     

African ancestry of the population of Buenos Aires

The population of Argentina today does not have a “visible” black African component. However, censuses conducted during most of the 19th century registered up to 30% of individuals of African origin living in Buenos Aires city. What has happened to this African influence? Have all individuals of African origin died, as lay people believe? Or is it possible that admixture with the European immigrants made the African influence “invisible?” We investigated the African contribution to the genetic pool of the population of Buenos Aires, Argentina, typing 12 unlinked autosomal DNA markers in a sample of 90 individuals. The results of this analysis suggest that 2.2% (SEM = 0.9%) of the genetic ancestry of the Buenos Aires population is derived from Africa. Our analysis of individual admixture shows that those alleles that have a high frequency in populations of African origin tend to concentrate among 8 individuals in our sample. Therefore, although the admixture estimate is relatively low, the actual proportion of individuals with at least some African influence is approximately 10%. The evidence we are presenting of African ancestry is consistent with the known historical events that led to the drastic reduction of the Afro‐Argentine population during the second half of the 19th century. However, as our results suggest, this reduction did not mean a total disappearance of African genes from the genetic pool of the Buenos Aires population. Am J Phys Anthropol 128:164‐170, 2005. © 2005 Wiley‐Liss, Inc.     

Population dynamics of Gila trout in the Gila River drainage of the south-western United States

In some small, often unstable, streams of the Gila River drainage, New Mexico, Gila trout Oncorhynchus gilae populations fluctuated numerically seasonally and annually. Few differences were noted in length-weight and size-structure comparisons, but Fulton condition index varied significantly. Time of sample and time since disturbance (natural or human-caused) were often associated with differences in condition. Other factors may include availability of prey, cannibalism, and reproductive condition. The repeatedly sampled McKnight Creek population illustrated the resilience of Gila trout populations to natural disturbances. A scouring flood in 1988 caused a >90% reduction in numbers, but, by 1992, population structure was not substantially different from that of other streams. Likewise, juvenile/adult ratio, density, and per cent large specimens (≥ 200 mm total length) of most other samples were within the ranges for the McKnight Creek population. Gila trout density (no. fish min⁻¹ electrofishing) tended to increase with higher elevation and greater drainage density (stream km catchment⁻¹ km⁻²) but decreased with larger catchments. Information gained in this study demonstrates that a variety of factors must be considered when evaluating the relative well-being of Gila trout populations and illustrates the importance of larger, more hydrologically complex drainages to the long-term survival of Gila trout populations.     

Gm3;5,13,14 and type 2 diabetes mellitus: an association in American Indians with genetic admixture.

In a sample of 4,920 Native Americans of the Pima and Papago tribes, there is a very strong negative association between the Gm haplotype Gm3;5,13,14 and type 2--or non-insulin-dependent--diabetes mellitus (prevalence ratio = 0.27, 95% confidence interval 0.18-0.40). One might conclude from this observation that the absence of this haplotype--or the presence of a closely linked gene--is a causal risk factor for the disease. It is shown that Gm3;5,13,14 is a marker for Caucasian admixture, and it is most likely the presence of Caucasian alleles and the concomitant decrease of Indian alleles that lowers the risk for diabetes, rather than the direct action of the haplotype or of a closely linked locus. This study demonstrates both the potential confounding effect of admixture on the interpretation of disease association studies and the importance of considering genetic admixture (or excluding individuals with genetic admixture) in studies of genetic markers of disease. The relationship between this admixture marker and the prevalence of diabetes also suggests a strong genetic component in the susceptibility to type 2 diabetes in Pima and Papago Indians.     

Disentangling the effects of demography and selection in human history

Demographic events affect all genes in a genome, whereas natural selection has only local effects. Using publicly available data from 151 loci sequenced in both European-American and African-American populations, we attempt to distinguish the effects of demography and selection. To analyze large sets of population genetic data such as this one, we introduce "Perlymorphism," a Unix-based suite of analysis tools. Our analyses show that the demographic histories of human populations can account for a large proportion of effects on the level and frequency of variation across the genome. The African-American population shows both a higher level of nucleotide diversity and more negative values of Tajima's D statistic than does a European-American population. Using coalescent simulations, we show that the significantly negative values of the D statistic in African-Americans and the positive values in European-Americans are well explained by relatively simple models of population admixture and bottleneck, respectively. Working within these nonequilibrium frameworks, we are still able to show deviations from neutral expectations at a number of loci, including ABO and TRPV6. In addition, we show that the frequency spectrum of mutations--corrected for levels of polymorphism--is correlated with recombination rate only in European-Americans. These results are consistent with repeated selective sweeps in non-African populations, in agreement with recent reports using microsatellite data.     

Blood polymorphisms and racial admixture in two Brazilian populations

One thousand individuals from the southern population of Porto Alegre and 760 from the northeastern city of Natal were studied in relation to 12 and 8 genetic systems, respectively. The data thus gathered were used in different ways to estimate quantitatively the ethnic composition of individuals from these communities. More than half of the genes present in individuals classified as Black in Porto Alegre may be of White origin, while the Whites from this city have 8% of African alleles. The estimated degree of admixture in persons identified as White or Mixed in Natal is not much different among themselves. The ancestry of the total sample can be characterized as 58% White, 25% Black, and 17% Indian.     

Body fat and racial genetic admixture are associated with aerobic fitness levels in a multiethnic pediatric population

Aerobic fitness and adiposity are each independently associated with health outcomes among children, although the relationship between these two variables is unclear. Our objectives were to evaluate (i) the association of adiposity with aerobic fitness using objectively measured levels of percent body fat, compared to BMI as a percentile proxy for adiposity while controlling for genetic admixture, and (ii) the congruence of BMI categories with high and low body fat categories of objectively measured percent body fat. Participants were 232 African-American (AA), European-American (EA), and Hispanic-American (HA) children aged 7-12 years (Tanner stage <3). Aerobic fitness was measured via a submaximal indirect calorimetry treadmill test (VO(2-170)), and physical activity levels with accelerometry. Genetic admixture estimates were obtained using 140 genetic ancestry informative markers to estimate European, African, and Amerindian admixture. Fat mass was determined using dual-energy x-ray absorptiometry (DXA). Children were classified into a low body fat group (<25% in males, <30% in females) or a high body fat group based on their percent body fat; children were also categorized according to BMI percentile. Children in the low body fat group had significantly higher aerobic fitness (P < 0.05) regardless of BMI percentile classification. Higher African genetic admixture was associated with lower aerobic fitness (P < 0.05), while physical activity was positively associated with fitness (P < 0.01). In conclusion, aerobic fitness levels differ by percent body fat and genetic admixture irrespective of BMI classification, and such differences should be taken into account when evaluating outcomes of health interventions.     

Admixture analysis of South Asian cattle

We present population genetic analysis of microsatellite variation in seven Bos indicus cattle breeds from a variety of locations in South Asia. This is the first such study focusing within this area, which is one of the postulated centres of origin of domestic cattle. An estimate of the influence of Bos taurus ancestry was carried out using three approaches: by the systematic selection of population-associated alleles for B. taurus and examination of their frequency; by examining the truncation of genetic distances from European populations; and by a model-based Bayesian admixture analysis. These analyses revealed a B. taurus influence in the Indian subcontinent; part of a gradation which stretches from Europe through the Near East towards Indian and which may be of ancient origin.