Genetic Structure Of Human Populations Research Articles

Genetic Affinities and Adaptation of the South-West Coast Populations of India.

Evolutionary event has not only altered the genetic structure of human populations but also associated with social and cultural transformation. South Asian populations were the result of migration and admixture of genetically and culturally diverse groups. Most of the genetic studies pointed to large-scale admixture events between Ancestral North Indian (ANI) and Ancestral South Indian (ASI) groups, also additional layers of recent admixture. In the present study, we have analyzed 213 individuals inhabited in South-west coast India with traditional warriors and feudal lord status and historically associated with migratory events from North/North West India and possible admixture with West Eurasian populations, whose genetic links are still missing. Analysis of autosomal Single Nucleotide Polymorphism (SNP) markers suggests that these groups possibly derived their ancestry from some groups of North West India having additional Middle Eastern genetic components. Higher distribution of West Eurasian mitochondrial haplogroups also points to female-mediated admixture. Estimation of Effective Migration Surface (EEMS) analysis indicates Central India and Godavari basin as a crucial transition zone for population migration from North and North West India to South-west coastal India. Selection screen using 3 distinct outlier-based approaches revealed genetic signatures related to Immunity and protection from Viral infections. Thus, our study suggests that the South-west coastal groups with traditional warriors and feudal lords' status are of a distinct lineage compared to Dravidian and Gangetic plain Indo-Europeans and are remnants of very early migrations from North West India following the Godavari basin to Karnataka and Kerala.

TCF7L2 gene polymorphism in populations of f ive Siberian ethnic groups.

Investigation of the frequencies of functionally signif icant gene variants in the context of medical biology and gene geography is a relevant issue for studying the genetic structure of human populations. The transition from a traditional to an urbanized lifestyle leads to a higher incidence of civilizational diseases associated with metabolic disorders, including type 2 diabetes mellitus. The goal of the present paper is to analyze the frequencies of functionally signif icant gene alleles in the metabolic prof iles of indigenous Siberian peoples to identify the gene pool resilience, evaluate the susceptibility of various ethnic groups to metabolic disorders under changing environmental conditions, and predict the epidemiological situation that may occur in the near future. The study was performed in the monoethnic samples of eastern and western Buryats, Teleuts, Dolgans, and two territorial groups of Yakuts. A real-time PCR was used to determine the frequencies of single nucleotide polymorphisms (SNPs) G103894T, rs12255372, and C53341T, rs7903146 in the TCF7L2 gene. The results obtained were compared to the frequencies identif ied for Russians from Eastern Siberia and the values available in the literature. The frequencies of the polymorphic variants studied in the samples from the indigenous Siberian peoples place them in between Caucasian and East Asian populations, following the geographic gradient of polymorphism distribution. A signif icantly lower occurrence of type 2 diabetes risk alleles TCF7L2 (103894T) and TCF7L2 (53341T) in the samples of indigenous Siberian peoples compared to Russians was observed, which agrees with their lower susceptibility to metabolic disorders compared to the newcomer Caucasian population. Taking into account urbanization, a reduced growth in type 2 diabetes incidence may be predicted in indigenous Siberian peoples, i. e. Buryats, Yakuts, Dolgans, and Teleuts, compared to the newcomer Caucasian population. A further study of population structure with respect to different metabolic prof ile genes is required to better understand the molecular genetic foundations of the adaptive potential of indigenous Siberian peoples

Defining Germline Predisposition to Dnmt3a-Mutant Clonal Hematopoiesis (CH)

Clonal hematopoiesis (CH) is the result of somatic mutations that confer a selective advantage to hematopoietic stem cells (HSCs), driving them to outcompete other HSCs and dominate mature hematopoietic cell production. While it is estimated that by middle age nearly all healthy individuals will have low but detectable variant allele frequency (VAF) indicating CH, only a small fraction will progress to hematologic malignancy. No methods currently exist to predict who will or will not progress to hematologic malignancy and preventative therapeutic strategies are lacking, largely due to poor understanding of the risk factors that determine whether individuals are susceptible to, or protected from, CH. Several recent population sequencing studies have found that inherited genetic variants increase the likelihood of developing CH and that there are population differences in clonal advantages gained by specific mutations in particular genetic and environmental contexts. Limitations of these human studies are the insufficient ability to control for and distinguish genetic from environmental contributions to CH, and to directly interrogate mechanisms causing genetic predisposition to CH and progression to malignancy. To overcome these barriers, here we have utilized the eight inbred and wild-derived founder strains of the Collaborative Cross (CC) and Diversity Outbred (DO) mouse populations (Saul MC et al., Trends in Genetics 2019). These feature well-characterized, segregated genetic variation that accurately reflects the genetic structure of human populations in a controlled environment. We crossed our recently described mouse model of CH (Dnmt3aR878H/+Mx1-Cre on a C57BL/6 background) (Loberg MA et al., Leukemia 2019) with each of the eight founder strains. We observed that genetic background conferred sensitivity or resistance to Dnmt3aR878H/+ HSC expansion based on phenotypic cell surface markers (Lin- c-Kit+ Sca-1+ CD150+ CD48-), relative to Dnmt3a+/+Mx1-Cre strain littermate controls. Genetic contribution from the C57BL/6 and CAST strains permitted robust Dnmt3aR878H/+ HSC expansion compared to Dnmt3a+/+ controls over a period of 6 months. In this same time frame, genetic contribution from 129, NOD, NZO, A/J, PWK, WSB strains demonstrated a spectrum of resistance to Dnmt3aR878H/+ HSC expansion. In vitro studies using colony-forming assays of bone marrow cells isolated from selected strains show a positive correlation between serial replating efficiency and phenotypic HSC frequency, supporting that phenotypic cell surface markers reliably define cells with functional potential across these strains. Ongoing studies to interrogate in vivo functional potential by competitive transplantation of HSCs isolated from each of these strains will be discussed. Together, our work demonstrates that HSC expansion as a consequence of Dnmt3a mutation is influenced by heritable genetic background in a controlled environmental setting. Understanding the mechanisms, at the systemic, intracellular and/or molecular levels, by which genetic background modifies HSC expansion caused by Dnmt3a or other CH mutations will be critical to develop improved prognostic tools and therapeutics to diagnose and treat high-risk versus low-risk CH. For this, utilization of genetically diverse mouse populations provides a critically needed platform to determine causative mechanisms driving clonal expansion of HSCs. Disclosures Trowbridge: Fate Therapeutics: Patents & Royalties: patent license.

Analysis of the mitochondrial CYTB gene sequence in human populations of northeastern Bosnia

This study offers the first report on variation sequence of the mitochondrial cytochrome b (MTCYTB) gene in populations from Bosnia (northeastern Bosnia). This study was designed on the analysis of the genetic diversity of two populations of different cultural-anthropological and genetic origin, Roma population and native/non-Roma population. The main aim of our study was to estimate the usefulness of the CYTB sequence in the analysis of genetic categorization of different populations and intergroup diversity, as well as to provide some additional information on haplogroup-associated polymorphisms within the CYTB region in defining haplogroup status. Estimation of the genetic diversity was done using intra and intergroup genetic indices. The population-specific polymorphisms have been found in both categories of the populations. The results of the analysis of genetic differentiation show significant pairwise Fst differences between the Romani and native populations. Also, registered significant genetic differentiation is illustrated on the level of genetic variation between subpopulations of the Roma and non-Roma origin. The important result in our study is the confirmation of the significance of the triad of polymorphisms T14783C-G15043A-G15301A, indicating the influence of Asian component of the maternal gene pool on the genetic structure of the studied population of the Roma. Our data show that the haplogroup polymorphisms exist in the CYTB region and can provide useful information on the haplogroups that were defined only by the control region of the mtDNA. The results of this study indicate the region of CYTB gene can be a benefit in providing some additional information in the analysis of genetic structure of human populations and can be additionally applied in population studies.

Habitat suitability and the genetic structure of human populations during the Last Glacial Maximum (LGM) in Western Europe.

Human populations in Western Europe during the Last Glacial Maximum were geographically constrained to glacial refugia by the severity of the climate and ecological risk factors. In this research we use an agent-based model of human mobility and interaction, based on ethnographic and archaeological data, to explore the impact of ecological risk on human population structure via a reconstructed landscape of habitat suitability. The agent-based model allows us to evaluate the size and location of glacial refugia, the size of the populations occupying them and the degree of genetic relatedness between people occupying these areas. To do this, we model the probability of an agent foraging groups’ survival as a function of habitat suitability. The model’s simulated “genomes” (composed of regionally specific genetic markers) allow us to track long-term trends of inter-regional interaction and mobility. The results agree with previous archaeological studies situating a large glacial refugium spanning southern France and northeastern Spain, but we expand on those studies by demonstrating that higher rates of population growth in this central refugium led to continuous out-migration and therefore genetic homogeneity across Western Europe, with the possible exception of the Italian peninsula. These results concur with material culture data from known archaeological sites dating to the Last Glacial Maximum and make predictions for future ancient DNA studies.

Evaluation of whole exome sequencing as an alternative to BeadChip and whole genome sequencing in human population genetic analysis

BackgroundUnderstanding the underlying genetic structure of human populations is of fundamental interest to both biological and social sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation. The most widely used methods for collecting variant information at the DNA-level include whole genome sequencing, which remains costly, and the more economical solution of array-based techniques, as these are capable of simultaneously genotyping a pre-selected set of variable DNA sites in the human genome. The largest publicly accessible set of human genomic sequence data available today originates from exome sequencing that comprises around 1.2% of the whole genome (approximately 30 million base pairs).ResultsTo unbiasedly compare the effect of SNP selection strategies in population genetic analysis we subsampled the variants of the same highly curated 1 K Genome dataset to mimic genome, exome sequencing and array data in order to eliminate the effect of different chemistry and error profiles of these different approaches. Next we compared the application of the exome dataset to the array-based dataset and to the gold standard whole genome dataset using the same population genetic analysis methods.ConclusionsOur results draw attention to some of the inherent problems that arise from using pre-selected SNP sets for population genetic analysis. Additionally, we demonstrate that exome sequencing provides a better alternative to the array-based methods for population genetic analysis. In this study, we propose a strategy for unbiased variant collection from exome data and offer a bioinformatics protocol for proper data processing.

Are Clusters Races? A Discussion of the Rhetorical Appropriation of Rosenberg et al.’s “Genetic Structure of Human Populations”

Noah Rosenberg et al.'s 2002 article “Genetic Structure of Human Populations” reported that multivariate genomic analysis of a large cell line panel yielded reproducible groupings (clusters) suggestive of individuals' geographical origins. The paper has been repeatedly cited as evidence that traditional notions of race have a biological basis, a claim its authors do not make. Critics of this misinterpretation have often suggested that it follows from interpreters' personal biases skewing the reception of an objective piece of scientific writing. I contend, however, that the article itself to some degree facilitates this misrepresentation. I analyze in detail several verbal and visual features of the original article that may predispose aspects of its racial interpretation; and, tracing the arguments of one philosopher and one popular science writer, I show how these features are absorbed, transformed into arguments for a biological basis of race, and re-attributed to the original. The essay demonstrates how even slight ambiguities can enable the misappropriation of scientific writing, unintentionally undermining the authors' stated circumspection on the relationship between cluster and race.

A longitudinal cline characterizes the genetic structure of human populations in the Tibetan plateau.

Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their demography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with worldwide genetic variation data. We found a clear signal of genetic stratification across the east-west axis within Tibetan samples. Samples from more eastern locations tend to have higher genetic affinity with lowland East Asians, which can be explained by more gene flow from lowland East Asia onto the plateau. Our findings corroborate a previous report of admixture signals in Tibetans, which were based on a subset of the samples analyzed here, but add evidence for isolation by distance in a broader geospatial context.

Detecting Heterogeneity in Population Structure Across the Genome in Admixed Populations.

The genetic structure of human populations is often characterized by aggregating measures of ancestry across the autosomal chromosomes. While it may be reasonable to assume that population structure patterns are similar genome-wide in relatively homogeneous populations, this assumption may not be appropriate for admixed populations, such as Hispanics and African-Americans, with recent ancestry from two or more continents. Recent studies have suggested that systematic ancestry differences can arise at genomic locations in admixed populations as a result of selection and nonrandom mating. Here, we propose a method, which we refer to as the chromosomal ancestry differences (CAnD) test, for detecting heterogeneity in population structure across the genome. CAnD can incorporate either local or chromosome-wide ancestry inferred from SNP genotype data to identify chromosomes harboring genomic regions with ancestry contributions that are significantly different than expected. In simulation studies with real genotype data from phase III of the HapMap Project, we demonstrate the validity and power of CAnD. We apply CAnD to the HapMap Mexican-American (MXL) and African-American (ASW) population samples; in this analysis the software RFMix is used to infer local ancestry at genomic regions, assuming admixing from Europeans, West Africans, and Native Americans. The CAnD test provides strong evidence of heterogeneity in population structure across the genome in the MXL sample ([Formula: see text]), which is largely driven by elevated Native American ancestry and deficit of European ancestry on the X chromosomes. Among the ASW, all chromosomes are largely African derived and no heterogeneity in population structure is detected in this sample.

Genetic structure of human populations based on 5 gene loci: A preliminary report from Northern India

The genetics of human populations reveals the evolutionary causes of population structure, population history, human diversity, racial divergence, adaptation, cultural and social behaviors and understanding human adaptation to local environmental constraints. The study aimed to determine the genetic relationship among six human population of Jammu and Kashmir, Northern India. This preliminary effort involved five gene loci of genetic traits, viz. ABO and Rh blood type, phenylthiocarbamide, color blindness and sickle cell trait. A total of 3679 healthy subjects were selected from six Muslim populations viz., Gujjar and Bakarwal (n=762), Mughal (n=560), Khan (n=642), Malik (n=564), Mir (579) and Syed (n=572). The allele frequencies and heterozygosity levels show significant differences among six populations (p<0.05). The phylogentic tree revealed that Mughal and Gujjar and Bakarwal (tribal population) are close to each other and differ from other four populations (Malik, Mir, Khan and Syed). Further studies in context genomic diversity, history and origin of these populations will be undertaken in future to get more conclusive proof.

Characterization of the biological processes shaping the genetic structure of the Italian population.

BackgroundThe genetic structure of human populations is the outcome of the combined action of different processes such as demographic dynamics and natural selection. Several efforts toward the characterization of population genetic architectures and the identification of adaptation signatures were recently made. In this study, we provide a genome-wide depiction of the Italian population structure and the analysis of the major determinants of the current existing genetic variation.ResultsWe defined and characterized 210 genomic loci associated with the first Principal Component calculated on the Italian genotypic data and correlated to the North–south genetic gradient. Using a gene-enrichment approach we identified the immune function as primarily involved in the Italian population differentiation and we described a locus on chromosome 13 showing combined evidence of North–south diversification in allele frequencies and signs of recent positive selection. In this region our bioinformatics analysis pinpointed an uncharacterized long intergenic non-coding (lincRNA), whose expression appeared specific for immune-related tissues suggesting its relevance for the immune function.ConclusionsOur study, combining population genetic analyses with biological insights provides a description of the Italian genetic structure that in future could contribute to the evaluation of complex diseases risk in the population context.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0293-x) contains supplementary material, which is available to authorized users.

Differential Evolution approach to detect recent admixture.

The genetic structure of human populations is extraordinarily complex and of fundamental importance to studies of anthropology, evolution, and medicine. As increasingly many individuals are of mixed origin, there is an unmet need for tools that can infer multiple origins. Misclassification of such individuals can lead to incorrect and costly misinterpretations of genomic data, primarily in disease studies and drug trials. We present an advanced tool to infer ancestry that can identify the biogeographic origins of highly mixed individuals. reAdmix can incorporate individual's knowledge of ancestors (e.g. having some ancestors from Turkey or a Scottish grandmother). reAdmix is an online tool available at http://chcb.saban-chla.usc.edu/reAdmix/.

Rare variation facilitates inferences of fine-scale population structure in humans.

Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European–American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies.

Detecting Genetic Isolation in Human Populations: A Study of European Language Minorities

The identification of isolation signatures is fundamental to better understand the genetic structure of human populations and to test the relations between cultural factors and genetic variation. However, with current approaches, it is not possible to distinguish between the consequences of long-term isolation and the effects of reduced sample size, selection and differential gene flow. To overcome these limitations, we have integrated the analysis of classical genetic diversity measures with a Bayesian method to estimate gene flow and have carried out simulations based on the coalescent. Combining these approaches, we first tested whether the relatively short history of cultural and geographical isolation of four “linguistic islands” of the Eastern Alps (Lessinia, Sauris, Sappada and Timau) had left detectable signatures in their genetic structure. We then compared our findings to previous studies of European population isolates. Finally, we explored the importance of demographic and cultural factors in shaping genetic diversity among the groups under study. A combination of small initial effective size and continued genetic isolation from surrounding populations seems to provide a coherent explanation for the diversity observed among Sauris, Sappada and Timau, which was found to be substantially greater than in other groups of European isolated populations. Simulations of micro-evolutionary scenarios indicate that ethnicity might have been important in increasing genetic diversity among these culturally related and spatially close populations.

The influence of habitats on female mobility in Central and Western Africa inferred from human mitochondrial variation

BackgroundWhen studying the genetic structure of human populations, the role of cultural factors may be difficult to ascertain due to a lack of formal models. Linguistic diversity is a typical example of such a situation. Patrilocality, on the other hand, can be integrated into a biological framework, allowing the formulation of explicit working hypotheses. The present study is based on the assumption that patrilocal traditions make the hypervariable region I of the mtDNA a valuable tool for the exploration of migratory dynamics, offering the opportunity to explore the relationships between genetic and linguistic diversity. We studied 85 Niger-Congo-speaking patrilocal populations that cover regions from Senegal to Central African Republic. A total of 4175 individuals were included in the study.ResultsBy combining a multivariate analysis aimed at investigating the population genetic structure, with a Bayesian approach used to test models and extent of migration, we were able to detect a stepping-stone migration model as the best descriptor of gene flow across the region, with the main discontinuities corresponding to forested areas.ConclusionsOur analyses highlight an aspect of the influence of habitat variation on human genetic diversity that has yet to be understood. Rather than depending simply on geographic linear distances, patterns of female genetic variation vary substantially between savannah and rainforest environments. Our findings may be explained by the effects of recent gene flow constrained by environmental factors, which superimposes on a background shaped by pre-agricultural peopling.

When gender matters: new insights into the relationships between social systems and the genetic structure of human populations

Due to its important effects on the ecological dynamics and the genetic structure of species, biologists have long been interested in gender-biased dispersal, a condition where one gender is more prone to move from the natal site. More recently, this topic has attracted a great attention from human evolutionary geneticists. Considering the close relations between residential rules and social structure, gender-biased dispersal is, in fact, regarded as an important case study concerning the effects of socio-cultural factors on human genetic variation. It all started with the seminal paper by Mark Seielstad, Erich Minch and Luigi Luca Cavalli Sforza from Stanford University (Seielstad et al. 1998). They observed a larger differentiation for Y-chromosome than mitochondrial DNA between extant human populations, purportedly a consequence of the prevalence of long-term patrilocality in human societies. Subsequent studies, however, have highlighted the need to consider geographically close and culturally homogeneous groups, disentangle signals due to different peopling events and obtain unbiased estimates of genetic diversity. In this issue of Molecular Ecology, not only do Marks et al. (2012) adopt an experimental design which addresses these concerns, but they also take a further and important step forward by integrating the genetic analysis of two distant populations, the Basotho and Spanish, with data regarding migration rates and matrimonial distances. Using both empirical evidence and simulations, the authors show that female-biased migration due to patrilocality might shape the genetic structure of human populations only at short ranges and under substantial differences in migration rates between genders. Providing a quantitative framework for future studies of the effects of residential rules on the human genome, this study paves the way for further developments in the field. On a wider perspective, Marks et al.'s work demonstrates the power of approaches which integrate biological, cultural and demographic lines of evidence in the study of relations between social and genetic structures of human populations.

Mitochondrial DNA sequence diversity in three ethnic populations from the South-west Iran: a preliminary study

To investigate the genetic structure of human populations in the South-west region of Iran, mitochondrial first hypervariable DNA sequences were obtained from 50 individuals representing three different ethnic groups from Khuzestan Province. Studied groups were Shushtari Persians and Chahar Lang Bakhtiyaries from Indo-European-speaking populations and Bani Torof Arabs from Semitic-speaking linguistic families. Genetic analysis of mtDNA data showed high similarity of Chahar Lang Bakhtiyaries with other Iranian Indo-European-speaking populations while Shushtaries and Bani Torofs had a closer affinity with Semitic-speaking groups rather than to other Iranian populations. The relationship of Chahar Lang Bakhtiyaries and Bani Torof Arabs with their neighbor populations can be explained by linguistic and geographic proximity. Whereas, the greater similarity of Shushtari Persians with West Asian Arabs is probably according to high gene flow between them. This article represents a preliminary study of three major ethnic groups of South-west Iran which investigates the potential genetic substructure of the region.

ANCIENT URBANIZATION PREDICTS GENETIC RESISTANCE TO TUBERCULOSIS

A link between urban living and disease is seen in recent and historical records, but the presence of this association in prehistory has been difficult to assess. If the transition to urban living does result in an increase in disease-based mortality, we might expect to see evidence of increased disease resistance in longer-term urbanized populations, as the result of natural selection. To test this, we determined the frequency of an allele (SLC11A1 1729 + 55del4) associated with natural resistance to intracellular pathogens such as tuberculosis and leprosy. We found a highly significantly correlation with duration of urban settlement-populations with a long history of living in towns are better adapted to resisting these infections. This correlation remains strong when we correct for autocorrelation in allele frequencies due to shared population history. Our results therefore support the interpretation that infectious disease loads became an increasingly important cause of human mortality after the advent of urbanization, highlighting the importance of population density in determining human health and the genetic structure of human populations.

A genomic analysis identifies a novel component in the genetic structure of sub-Saharan African populations

Studies of large sets of single nucleotide polymorphism (SNP) data have proven to be a powerful tool in the analysis of the genetic structure of human populations. In this work, we analyze genotyping data for 2841 SNPs in 12 sub-Saharan African populations, including a previously unsampled region of southeastern Africa (Mozambique). We show that robust results in a world-wide perspective can be obtained when analyzing only 1000 SNPs. Our main results both confirm the results of previous studies, and show new and interesting features in sub-Saharan African genetic complexity. There is a strong differentiation of Nilo-Saharans, much beyond what would be expected by geography. Hunter-gatherer populations (Khoisan and Pygmies) show a clear distinctiveness with very intrinsic Pygmy (and not only Khoisan) genetic features. Populations of the West Africa present an unexpected similarity among them, possibly the result of a population expansion. Finally, we find a strong differentiation of the southeastern Bantu population from Mozambique, which suggests an assimilation of a pre-Bantu substrate by Bantu speakers in the region.

Genes predict village of origin in rural Europe

The genetic structure of human populations is important in population genetics, forensics and medicine. Using genome-wide scans and individuals with all four grandparents born in the same settlement, we here demonstrate remarkable geographical structure across 8-30 km in three different parts of rural Europe. After excluding close kin and inbreeding, village of origin could still be predicted correctly on the basis of genetic data for 89-100% of individuals.