High-density SNP genotyping detects homogeneity of Spanish and French Basques, and confirms their genomic distinctiveness from other European populations
A recent study reported that Basques do not constitute a genetically distinct population, and that Basques from Spanish and French provinces do not show significant genetic similarity. These conclusions disagree with numerous previous studies, and are not consistent with the historical and linguistic evidence that supports the distinctiveness of Basques. In order to further investigate this controversy, we have genotyped 83 Spanish Basque individuals and used these data to infer population structure based on more than 60,000 single nucleotide polymorphisms of several European populations. Here, we present the first high-throughput analysis including Basques from Spanish and French provinces, and show that all Basques constitute a homogeneous group that can be clearly differentiated from other European populations.
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... The Basque Country is a region that spans parts of northern Spain and southwestern France. In recent years, autochthonous Basque inhabitants have garnered significant research attention due to their distinctive cultural, biological and genetic background from other European populations 16,17 . However, according to the Basque Institute of Statistics (EUSTAT), as of January 2022, nearly 30% of the current residents of the Basque Country were born in the remaining Spanish provinces and to foreigners (https:// en. ...
Adeno-associated viruses (AAVs) are promising gene therapy vectors, but challenges arise when treating patients with preexisting neutralizing antibodies. Worldwide seroprevalence studies provide snapshots of existing immunity in diverse populations. Owing to the uniqueness of the Basque socio-geographical landscape, we investigated the seroprevalence of eight AAV serotypes in residents of the Basque Country. We found the highest seroprevalence of AAV3, and the lowest seroprevalence of AAV9. Additionally, less than 50% of the Basque population has neutralizing antibodies against AAV4, AAV6, and AAV9. Our findings provide insight into AAV infections in the Basque region, public health, and the development of AAV-based therapeutics.
... In addition, our findings are consistent with previous studies reporting that Basques are distinct from other European populations and from North African [51,[61][62][63]. Otherwise, Walsh et al., (2013) assessed the sensitivity of the HIrisPlex system, which predicts eye and hair color by targeting 22 DNA variants. ...
... Arnaiz-Villena et al. 1999;Bertranpetit et al. 1995;Calderón et al. 2003;Comas et al. 2000;de Pancorbo et al. 2001;García-Obregón et al. 2007;Iriondo et al. 2003;Izagirre and De la Rúa 1999;Pereira et al. 2005;Rodríguez-Ezpeleta et al. 2010).In this paper, we analyze the way in which a group of European descendants integrated to the Uruguayan society and became part of its present-day population. Particularly, we aim to determine if Basque-descendants in Uruguay remained relatively isolated or if they mixed with other ethnic groups. ...
... Our result highlights other communities relevant to genetic mapping efforts, some that are well established in the literature such Orkney and Shetland (20,21,46,47) or the Basque (48)(49)(50)(51) and some novel, e.g., the Channel Islands. The Channel Islands are an archipelago of isles off the northern coast of France and are a British dependency. ...
Haplotype-based analyses have recently been leveraged to interrogate the fine-scale structure in specific geographic regions, notably in Europe, although an equivalent haplotype-based understanding across the whole of Europe with these tools is lacking. Furthermore, study of identity-by-descent (IBD) sharing in a large sample of haplotypes across Europe would allow a direct comparison between different demographic histories of different regions. The UK Biobank (UKBB) is a population-scale dataset of genotype and phenotype data collected from the United Kingdom, with established sampling of worldwide ancestries. The exact content of these non-UK ancestries is largely uncharacterized, where study could highlight valuable intracontinental ancestry references with deep phenotyping within the UKBB. In this context, we sought to investigate the sample of European ancestry captured in the UKBB. We studied the haplotypes of 5,500 UKBB individuals with a European birthplace; investigated the population structure and demographic history in Europe, showing in parallel the variety of footprints of demographic history in different genetic regions around Europe; and expand knowledge of the genetic landscape of the east and southeast of Europe. Providing an updated map of European genetics, we leverage IBD-segment sharing to explore the extent of population isolation and size across the continent. In addition to building and expanding upon previous knowledge in Europe, our results show the UKBB as a source of diverse ancestries beyond Britain. These worldwide ancestries sampled in the UKBB may complement and inform researchers interested in specific communities or regions not limited to Britain.
The former Kingdom of Granada, comprising the provinces of Granada, Málaga, and Almería (GMA), was once inhabited for over 700 years (711–1492 AD) by a North African population, which influenced its creation and establishment. The genetic data on 15 autosomal short tandem repeats (STRs) in 245 unrelated donor residents were examined in order to assess any possible admixture. As the two surnames in Spain follow an inheritance similar to the Y chromosome, both surnames of all 245 unrelated individuals were queried and annotated. The Spanish Statistics Office website was consulted to determine the regions with the highest frequency of individuals born bearing each surname. Further, several heraldry and lineage pages were examined to determine the historical origin of the surnames. By AMOVA and STRUCTURE analysis, the populations of the three provinces can be treated genetically as a single population. The analysis of allele frequencies and genetic distance demonstrated that the GMA population lay in the Spanish population group but was slightly more similar to the North African populations than the remainder of the Spanish populations. In addition, the surnames of most individuals originated in Northern and Central Spain, whereas most surnames had higher frequencies in Southern Spain. These results confirm that the GMA population shows no characteristics that reflect a greater genetic influence of North African people than the rest of the populations of the Iberian Peninsula. This feature is consistent with the historical data that African inhabitants were expelled or isolated during the repopulation of the region with Spaniards from Northern Spain. The knowledge of present populations and their genetic history is essential for better statistical results in kinship analyses.
Researchers have long had an interest in dental morphology as a genetic proxy to reconstruct population history. Much interest was fostered by the use of standard plaques and associated descriptions that comprise the Arizona State University Dental Anthropology System, developed by Christy G. Turner, II and students. This system has served as the foundation for hundreds of anthropological studies for over 30 years. In recognition of that success, this volume brings together some of the world's leading dental morphologists to expand upon the concepts and methods presented in the popular The Anthropology of Modern Human Teeth (Cambridge, 1997), leading the reader from method to applied research. After a preparatory section on the current knowledge of heritability and gene expression, a series of case studies demonstrate the utility of dental morphological study in both fossil and more recent populations (and individuals), from local to global scales.
Researchers have long had an interest in dental morphology as a genetic proxy to reconstruct population history. Much interest was fostered by the use of standard plaques and associated descriptions that comprise the Arizona State University Dental Anthropology System, developed by Christy G. Turner, II and students. This system has served as the foundation for hundreds of anthropological studies for over 30 years. In recognition of that success, this volume brings together some of the world's leading dental morphologists to expand upon the concepts and methods presented in the popular The Anthropology of Modern Human Teeth (Cambridge, 1997), leading the reader from method to applied research. After a preparatory section on the current knowledge of heritability and gene expression, a series of case studies demonstrate the utility of dental morphological study in both fossil and more recent populations (and individuals), from local to global scales.
Researchers have long had an interest in dental morphology as a genetic proxy to reconstruct population history. Much interest was fostered by the use of standard plaques and associated descriptions that comprise the Arizona State University Dental Anthropology System, developed by Christy G. Turner, II and students. This system has served as the foundation for hundreds of anthropological studies for over 30 years. In recognition of that success, this volume brings together some of the world's leading dental morphologists to expand upon the concepts and methods presented in the popular The Anthropology of Modern Human Teeth (Cambridge, 1997), leading the reader from method to applied research. After a preparatory section on the current knowledge of heritability and gene expression, a series of case studies demonstrate the utility of dental morphological study in both fossil and more recent populations (and individuals), from local to global scales.
Why do individuals engage in violence against the state? This research investigates the biological and environmental determinants of individual-level participation in political violence through the use of a Candidate Gene Association, gene-environment interaction, study. Existing research has demonstrated that variation in a specific gene (called MAO-A) is associated with aggression. However, relatively little scholarly attention has been paid to the interaction with the environment; specifically, the ways in which repressive political environments differentially incite acts of violence. Using original genetic, survey and experimental data collected on participants and non-participants of political violence, I find that under conditions of political repression, individuals with the low MAO-A genetic variant are significantly more likely to engage in acts of political violence. By examining both the genetic and environmental factors influencing political violence, the results make a significant contribution to our understanding of how genetic variation may lead to violence.
One of the main challenges of human population genetics has been the reconstruction of the population history of humans at different scales, from the origin of the modern humans to the history of specific groups. In all cases information from other historical sciences (including archaeology, linguistics and physical anthropology) should match in the unique frame of population history. Cavalli-Sforza, had a pioneering role in defining the problem and putting together a database of classical genetic markers and statistical methods to make the genetic approach of high relevance. One of the problems studied refers to the Basque population, establishing its distinctiveness and “origin”. As in many other settings, research in the area in the last few decades has flourished by adding much DNA information and statistical analysis to corroborate or correct the initial hypotheses. In the case of the Basques, the differentiation without strong external genetic influences has been confirmed as due to isolation, and instead of being pre-Neolithic, it is currently dated to the Iron Age, only some 2,500 year ago. Based on: “Bertranpetit J, Cavalli-Sforza LL. A genetic reconstruction of the history of the population of the Iberian Peninsula. Ann Hum Genet 1991; 55:51-67.”
As we move forward from the current generation of genome-wide association (GWA) studies, additional cohorts of different ancestries will be studied to increase power, fine map association signals, and generalize association results to additional populations. Knowledge of genetic ancestry as well as population substructure will become increasingly important for GWA studies in populations of unknown ancestry. Here we propose genotyping pooled DNA samples using genome-wide SNP arrays as a viable option to efficiently and inexpensively estimate admixture proportion and identify ancestry informative markers (AIMs) in populations of unknown origin. We constructed DNA pools from African American, Native Hawaiian, Latina, and Jamaican samples and genotyped them using the Affymetrix 6.0 array. Aided by individual genotype data from the African American cohort, we established quality control filters to remove poorly performing SNPs and estimated allele frequencies for the remaining SNPs in each panel. We then applied a regression-based method to estimate the proportion of admixture in each cohort using the allele frequencies estimated from pooling and populations from the International HapMap Consortium as reference panels, and identified AIMs unique to each population. In this study, we demonstrated that genotyping pooled DNA samples yields estimates of admixture proportion that are both consistent with our knowledge of population history and similar to those obtained by genotyping known AIMs. Furthermore, through validation by individual genotyping, we demonstrated that pooling is quite effective for identifying SNPs with large allele frequency differences (i.e., AIMs) and that these AIMs are able to differentiate two closely related populations (HapMap JPT and CHB).
The Basques are a culturally isolated population, living across the western border between France and Spain and speaking a non-Indo-European language. They show outlier allele frequencies in the ABO, RH, and HLA loci. To test whether Basques are a genetic isolate with the features that would make them good candidates in genetic association studies, we genotyped 123 SNPs in a 1-Mb region in chromosome 22 in Basque samples from France and Spain, as well as in samples from northern and southern Spain, and in three North African samples. Both Basque samples showed similar levels of heterozygosity to the other populations, and the decay of linkage disequilibrium with physical distance was not different between Basques and non-Basques. Thus, Basques do not show the genetic properties expected in population isolates.
We describe extensions to the method of Pritchard et al. for inferring population structure from multilocus genotype data. Most importantly, we develop methods that allow for linkage between loci. The new model accounts for the correlations between linked loci that arise in admixed populations (“admixture linkage disequilibium”). This modification has several advantages, allowing (1) detection of admixture events farther back into the past, (2) inference of the population of origin of chromosomal regions, and (3) more accurate estimates of statistical uncertainty when linked loci are used. It is also of potential use for admixture mapping. In addition, we describe a new prior model for the allele frequencies within each population, which allows identification of subtle population subdivisions that were not detectable using the existing method. We present results applying the new methods to study admixture in African-Americans, recombination in Helicobacter pylori, and drift in populations of Drosophila melanogaster. The methods are implemented in a program, structure, version 2.0, which is available at http://pritch.bsd.uchicago.edu.
In analysis of multilocus genotypes from structured populations, individual coefficients of membership in subpopulations are often estimated using programs such as structure. distruct provides a general method for visualizing these estimated membership coefficients. Subpopulations are represented as colours, and individuals are depicted as bars partitioned into coloured segments that correspond to membership coefficients in the subgroups. distruct, available at http://www.cmb.usc.edu/~noahr/distruct.html, can also be used to display subpopulation assignment probabilities when individuals are assumed to have ancestry in only one group.
Basques are a cultural isolate, and, according to mainly allele frequencies of classical polymorphisms, also a genetic isolate. We investigated the differentiation of Spanish Basques from the rest of Iberian populations by means of a dense, genome-wide SNP array. We found that F
ST distances between Spanish Basques and other populations were similar to those between pairs of non-Basque populations. The same result is found in a PCA of individuals, showing a general distinction between Iberians and other South Europeans independently of being Basques. Pathogen-mediated natural selection may be responsible for the high differentiation previously reported for Basques at very specific genes such as ABO, RH, and HLA. Thus, Basques cannot be considered a genetic outlier under a general genome scope and interpretations on their origin may have to be revised.
This is the version as published in the American Journal of Human Genetics by the University Of Chicago Press. Their website is http://www.journals.uchicago.edu/AJHG.home.html We have examined the worldwide distribution of a Y-chromosomal base-substitution polymorphism, the T/C transition at SRY-2627, where the T allele defines haplogroup 22; sequencing of primate homologues shows that the ancestral state cannot be determined unambiguously but is probably the C allele. Of 1,191 human Y chromosomes analyzed, 33 belong to haplogroup 22. Twenty-nine come from Iberia, and the highest frequencies are in Basques (11%; n=117) and Catalans (22%; n=32). Microsatellite and minisatellite (MSY1) diversity analysis shows that non-Iberian haplogroup-22 chromosomes are not significantly different from Iberian ones. The simplest interpretation of these data is that haplogroup 22 arose in Iberia and that non-Iberian cases reflect Iberian emigrants. Several different methods were used to date the origin of the polymorphism: microsatellite data gave ages of 1,650, 2,700, 3,100, or 3,450 years, and MSY1 gave ages of 1,000, 2,300, or 2,650 years, although 95% confidence intervals on all of these figures are wide. The age of the split between Basque and Catalan haplogroup-22 chromosomes was calculated as only 20% of the age of the lineage as a whole. This study thus provides evidence for direct or indirect gene flow over the substantial linguistic barrier between the Indo-European and non-Indo-European-speaking populations of the Catalans and the Basques, during the past few thousand years.
Different analyses of genetic polymorphisms performed on the Basque population have suggested a possible heterogeneity of the Basques and a singularity of their genetic characteristics. In this paper, both aspects are analyzed by means of the genetic study of seven polymorphic systems--ACP, ADA, AK, ESD, PGD, GC, and HP--in 854 autochthonous individuals from the province of Vizcaya. The individuals were classified as being from the regions of Arratia, Guernica, Durango, Uribe, Marquina, Lea, and Bilbao, on the basis of the birthplaces of their four grandparents. Analyses for heterogeneity of the gene frequencies distribution suggest that there is a moderate genetic heterogeneity, probably produced by centuries of geographical and administrative isolation of these regions. The comparison with caucasoid populations, performed using the principal components analysis and Cavalli-Sforza and Edwards arc distance, indicates that the subpopulations of the province of Vizcaya have experienced little genetic exchange with other caucasoids and that the distribution of their genetic frequencies differentiates them from other populations.