Publications by authors named "Francesc Calafell"

115 Publications

Uniparental markers and their role in the future of Molecular Anthropology.

J Anthropol Sci 2021 Sep 26;99. Epub 2021 Sep 26.

Departament de Ciències Experimentals i de la Salut, Institut de Biologia Evolutiva (UPF-CSIC), Universitat Pompeu Fabra, Barcelona, Spain,

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http://dx.doi.org/10.4436/JASS.99005DOI Listing
September 2021

Admixture Has Shaped Romani Genetic Diversity in Clinically Relevant Variants.

Front Genet 2021 16;12:683880. Epub 2021 Jun 16.

Departament de Ciències Experimentals i de la Salut, Institut de Biologia Evolutiva (UPF-CSIC), Universitat Pompeu Fabra, Barcelona, Spain.

Genetic patterns of inter-population variation are a result of different demographic and adaptive histories, which gradually shape the frequency distribution of the variants. However, the study of clinically relevant mutations has a Eurocentric bias. The Romani, the largest transnational minority ethnic group in Europe, originated in South Asia and received extensive gene flow from West Eurasia. Most medical genetic studies have only explored founder mutations related to Mendelian disorders in this population. Here we analyze exome sequences and genome-wide array data of 89 healthy Spanish Roma individuals to study complex traits and disease. We apply a different framework and focus on variants with both increased and decreased allele frequencies, taking into account their local ancestry. We report several OMIM traits enriched for genes with deleterious variants showing increased frequencies in Roma or in non-Roma (e.g., obesity is enriched in Roma, with an associated variant linked to South Asian ancestry; while non-insulin dependent diabetes is enriched in non-Roma Europeans). In addition, previously reported pathogenic variants also show differences among populations, where some variants segregating at low frequency in non-Roma are virtually absent in the Roma. Lastly, we describe frequency changes in drug-response variation, where many of the variants increased in Roma are clinically associated with metabolic and cardiovascular-related drugs. These results suggest that clinically relevant variation in Roma cannot only be characterized in terms of founder mutations. Instead, we observe frequency differences compared to non-Roma: some variants are absent, while other have drifted to higher frequencies. As a result of the admixture events, these clinically damaging variants can be traced back to both European and South Asian-related ancestries. This can be attributed to a different prevalence of some genetic disorders or to the fact that genetic susceptibility variants are mostly studied in populations of European descent, and can differ in individuals with different ancestries.
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http://dx.doi.org/10.3389/fgene.2021.683880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244592PMC
June 2021

Second GHEP-ISFG exercise for DVI: "DNA-led" victims' identification in a simulated air crash.

Forensic Sci Int Genet 2021 07 19;53:102527. Epub 2021 May 19.

PRICAI - Fundación Favaloro, CABA, Argentina. Electronic address:

The Spanish and Portuguese-Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) has organized a second collaborative exercise on a simulated case of Disaster Victim Identification (DVI), with the participation of eighteen laboratories. The exercise focused on the analysis of a simulated plane crash case of medium-size resulting in 66 victims with varying degrees of fragmentation of the bodies (with commingled remains). As an additional difficulty, this second exercise included 21 related victims belonging to 6 families among the 66 missings to be identified. A total number of 228 post-mortem samples were represented with aSTR and mtDNA profiles, with a proportion of partial aSTR profiles simulating charred remains. To perform the exercise, participants were provided with aSTR and mtDNA data of 51 reference pedigrees -some of which deficient-including 128 donors for identification purposes. The exercise consisted firstly in the comparison of the post-mortem genetic profiles in order to re-associate fragmented remains to the same individual and secondly in the identification of the re-associated remains by comparing aSTR and mtDNA profiles with reference pedigrees using pre-established thresholds to report a positive identification. Regarding the results of the post-mortem samples re-associations, only a small number of discrepancies among participants were detected, all of which were from just a few labs. However, in the identification process by kinship analysis with family references, there were more discrepancies in comparison to the correct results. The identification results of single victims yielded fewer problems than the identification of multiple related victims within the same family groups. Several reasons for the discrepant results were detected: a) the identity/non-identity hypotheses were sometimes wrongly expressed in the likelihood ratio calculations, b) some laboratories failed to use all family references to report the DNA match, c) In families with several related victims, some laboratories firstly identified some victims and then unnecessarily used their genetic information to identify the remaining victims within the family, d) some laboratories did not correctly use "prior odds" values for the Bayesian treatment of the episode for both post-mortem/post-mortem re-associations as well as the ante-mortem/post-mortem comparisons to evaluate the probability of identity. For some of the above reasons, certain laboratories failed to identify some victims. This simulated "DNA-led" identification exercise may help forensic genetic laboratories to gain experience and expertize for DVI or MPI in using genetic data and comparing their own results with the ones in this collaborative exercise.
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http://dx.doi.org/10.1016/j.fsigen.2021.102527DOI Listing
July 2021

Genetic origins, singularity, and heterogeneity of Basques.

Curr Biol 2021 May 25;31(10):2167-2177.e4. Epub 2021 Mar 25.

Departament de Ciències de la Salut i de la Vida, Institut de Biologia Evolutiva (CSIC-UPF), Universitat Pompeu Fabra, Barcelona 08003, Spain. Electronic address:

Basques have historically lived along the Western Pyrenees, in the Franco-Cantabrian region, straddling the current Spanish and French territories. Over the last decades, they have been the focus of intense research due to their singular cultural and biological traits that, with high controversy, placed them as a heterogeneous, isolated, and unique population. Their non-Indo-European language, Euskara, is thought to be a major factor shaping the genetic landscape of the Basques. Yet there is still a lively debate about their history and assumed singularity due to the limitations of previous studies. Here, we analyze genome-wide data of Basque and surrounding groups that do not speak Euskara at a micro-geographical level. A total of ∼629,000 genome-wide variants were analyzed in 1,970 modern and ancient samples, including 190 new individuals from 18 sampling locations in the Basque area. For the first time, local- and wide-scale analyses from genome-wide data have been performed covering the whole Franco-Cantabrian region, combining allele frequency and haplotype-based methods. Our results show a clear differentiation of Basques from the surrounding populations, with the non-Euskara-speaking Franco-Cantabrians located in an intermediate position. Moreover, a sharp genetic heterogeneity within Basques is observed with significant correlation with geography. Finally, the detected Basque differentiation cannot be attributed to an external origin compared to other Iberian and surrounding populations. Instead, we show that such differentiation results from genetic continuity since the Iron Age, characterized by periods of isolation and lack of recent gene flow that might have been reinforced by the language barrier.
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http://dx.doi.org/10.1016/j.cub.2021.03.010DOI Listing
May 2021

The Counteracting Effects of Demography on Functional Genomic Variation: The Roma Paradigm.

Mol Biol Evol 2021 06;38(7):2804-2817

Departament de Ciències Experimentals i de la Salut, Institut de Biologia Evolutiva (UPF-CSIC), Universitat Pompeu Fabra, Barcelona, Spain.

Demographic history plays a major role in shaping the distribution of genomic variation. Yet the interaction between different demographic forces and their effects in the genomes is not fully resolved in human populations. Here, we focus on the Roma population, the largest transnational ethnic minority in Europe. They have a South Asian origin and their demographic history is characterized by recent dispersals, multiple founder events, and extensive gene flow from non-Roma groups. Through the analyses of new high-coverage whole exome sequences and genome-wide array data for 89 Iberian Roma individuals together with forward simulations, we show that founder effects have reduced their genetic diversity and proportion of rare variants, gene flow has counteracted the increase in mutational load, runs of homozygosity show ancestry-specific patterns of accumulation of deleterious homozygotes, and selection signals primarily derive from preadmixture adaptation in the Roma population sources. The present study shows how two demographic forces, bottlenecks and admixture, act in opposite directions and have long-term balancing effects on the Roma genomes. Understanding how demography and gene flow shape the genome of an admixed population provides an opportunity to elucidate how genomic variation is modeled in human populations.
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http://dx.doi.org/10.1093/molbev/msab070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233508PMC
June 2021

Autosomal genetics and Y-chromosome haplogroup L1b-M317 reveal Mount Lebanon Maronites as a persistently non-emigrating population.

Eur J Hum Genet 2021 04 4;29(4):581-592. Epub 2020 Dec 4.

University of Balamand, East Med Res Institute, School of Medicine, P.O. Box 33, Amioun, Lebanon.

Currently, there are 18 different religious communities living in Lebanon. While evolving primarily within Lebanon, these communities show a level of local isolation as demonstrated previously from their Y-haplogroup distributions. In order to trace the origins and migratory patterns that may have led to the genetic isolation and autosomal clustering in some of these communities we analyzed Y-chromosome STR and SNP sample data from 6327 individuals, in addition to whole genome autosomal sample data from 609 individuals, from Mount Lebanon and other surrounding communities. We observed Y chromosome L1b Levantine STR branching that occurred around 5000 years ago. Autosomal DNA analyses suggest that the North Lebanese Mountain Maronite community possesses an ancestral Fertile Crescent genetic component distinct from other populations in the region. We suggest that the Levantine L1b group split from the Caucasus ancestral group around 7300 years ago and migrated to the Levant. This event was distinct from the earlier expansions from the Caucasus region that contributed to the wider Levantine populations. Differential cultural adaption by populations from the North Lebanese Mountains are clearly aligned with the L1b haplotype STR haplogroup clusters, indicating pre-existing and persistent cultural barriers marked by the transmission of L1b lineages. Our findings highlight the value of uniparental haplogroups and STR haplotype data for elucidating biosocial events among these populations.
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http://dx.doi.org/10.1038/s41431-020-00765-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182888PMC
April 2021

Recent Common Origin, Reduced Population Size, and Marked Admixture Have Shaped European Roma Genomes.

Mol Biol Evol 2020 11;37(11):3175-3187

Departament de Ciències Experimentals i de la Salut, Institut de Biologia Evolutiva (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain.

The Roma Diaspora-traditionally known as Gypsies-remains among the least explored population migratory events in historical times. It involved the migration of Roma ancestors out-of-India through the plateaus of Western Asia ultimately reaching Europe. The demographic effects of the Diaspora-bottlenecks, endogamy, and gene flow-might have left marked molecular traces in the Roma genomes. Here, we analyze the whole-genome sequence of 46 Roma individuals pertaining to four migrant groups in six European countries. Our analyses revealed a strong, early founder effect followed by a drastic reduction of ∼44% in effective population size. The Roma common ancestors split from the Punjabi population, from Northwest India, some generations before the Diaspora started, <2,000 years ago. The initial bottleneck and subsequent endogamy are revealed by the occurrence of extensive runs of homozygosity and identity-by-descent segments in all Roma populations. Furthermore, we provide evidence of gene flow from Armenian and Anatolian groups in present-day Roma, although the primary contribution to Roma gene pool comes from non-Roma Europeans, which accounts for >50% of their genomes. The linguistic and historical differentiation of Roma in migrant groups is confirmed by the differential proportion, but not a differential source, of European admixture in the Roma groups, which shows a westward cline. In the present study, we found that despite the strong admixture Roma had in their diaspora, the signature of the initial bottleneck and the subsequent endogamy is still present in Roma genomes.
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http://dx.doi.org/10.1093/molbev/msaa156DOI Listing
November 2020

The place of metropolitan France in the European genomic landscape.

Hum Genet 2020 Aug 7;139(8):1091-1105. Epub 2020 Apr 7.

Departament de Ciències Experimentals i de la Salut, Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Carrer Doctor Aiguader 88, 08005, Barcelona, Catalonia, Spain.

Unlike other European countries, the human population genetics and demographic history of Metropolitan France is surprisingly understudied. In this work, we combined newly genotyped samples from various zones in France with publicly available data and applied both allele frequency and haplotype-based methods to describe the internal structure of this country, using genome-wide single nucleotide polymorphism (SNP) array genotypes. We found out that French Basques, already known for their linguistic uniqueness, are genetically distinct from all other groups and that the populations from southwest France (namely the Gascony region) share a large proportion of their ancestry with Basques. Otherwise, the genetic makeup of the French population is relatively homogeneous and mostly related to Southern and Central European groups. However, a fine-grained, haplotype-based analysis revealed that Bretons slightly separated from the rest of the groups, due mostly to gene flow from the British Isles in a time frame that coincides both historically attested Celtic population movements to this area between the 3th and the ninth centuries CE, but also with a more ancient genetic continuity between Brittany and the British Isles related to the shared drift with hunter-gatherer populations. Haplotype-based methods also unveiled subtle internal structures and connections with the surrounding modern populations, particularly in the periphery of the country.
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http://dx.doi.org/10.1007/s00439-020-02158-yDOI Listing
August 2020

A Historical-Genetic Reconstruction of Human Extra-Pair Paternity.

Curr Biol 2019 12 14;29(23):4102-4107.e7. Epub 2019 Nov 14.

Laboratory of Socioecology and Social Evolution, Department of Biology, KU Leuven, Naamsestraat, Leuven 3000, Belgium.

Paternity testing using genetic markers has shown that extra-pair paternity (EPP) is common in many pair-bonded species [1, 2]. Evolutionary theory and empirical data show that extra-pair copulations can increase the fitness of males as well as females [3, 4]. This can carry a significant fitness cost for the social father, who then invests in rearing offspring that biologically are not his own [5]. In human populations, the incidence and correlates of extra-pair paternity remain highly contentious [2, 6, 7]. Here, we use a population-level genetic genealogy approach [6, 8] to reconstruct spatiotemporal patterns in human EPP rates. Using patrilineal genealogies from the Low Countries spanning a period of over 500 years and Y chromosome genotyping of living descendants, our analysis reveals that historical EPP rates, while low overall, were strongly impacted by socioeconomic and demographic factors. Specifically, we observe that estimated EPP rates among married couples varied by more than an order of magnitude, from 0.4% to 5.9%, and peaked among families with a low socioeconomic background living in densely populated cities of the late 19 century. Our results support theoretical predictions that social context can strongly affect the outcomes of sexual conflict in human populations by modulating the incentives and opportunities for engaging in extra-pair relationships [9-11]. These findings show how contemporary genetic data combined with in-depth genealogies open up a new window on the sexual behavior of our ancestors.
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http://dx.doi.org/10.1016/j.cub.2019.09.075DOI Listing
December 2019

European Roma groups show complex West Eurasian admixture footprints and a common South Asian genetic origin.

PLoS Genet 2019 09 23;15(9):e1008417. Epub 2019 Sep 23.

Institute of Evolutionary Biology (UPF-CSIC), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.

The Roma population is the largest transnational ethnic minority in Europe, characterized by a linguistic, cultural and historical heterogeneity. Comparative linguistics and genetic studies have placed the origin of European Roma in the Northwest of India. After their migration across Persia, they entered into the Balkan Peninsula, from where they spread into Europe, arriving in the Iberian Peninsula in the 15th century. Their particular demographic history has genetic implications linked to rare and common diseases. However, the South Asian source of the proto-Roma remains still untargeted and the West Eurasian Roma component has not been yet deeply characterized. Here, in order to describe both the South Asian and West Eurasian ancestries, we analyze previously published genome-wide data of 152 European Roma and 34 new Iberian Roma samples at a fine-scale and haplotype-based level, with special focus on the Iberian Roma genetic substructure. Our results suggest that the putative origin of the proto-Roma involves a Punjabi group with low levels of West Eurasian ancestry. In addition, we have identified a complex West Eurasian component (around 65%) in the Roma, as a result of the admixture events occurred with non-proto-Roma populations between 1270-1580. Particularly, we have detected the Balkan genetic footprint in all European Roma, and the Baltic and Iberian components in the Northern and Western Roma groups, respectively. Finally, our results show genetic substructure within the Iberian Roma, with different levels of West Eurasian admixture, as a result of the complex historical events occurred in the Peninsula.
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http://dx.doi.org/10.1371/journal.pgen.1008417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779411PMC
September 2019

People from Ibiza: an unexpected isolate in the Western Mediterranean.

Eur J Hum Genet 2019 06 14;27(6):941-951. Epub 2019 Feb 14.

Departament de Ciències Experimentals i de la Salut, Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Barcelona, Spain.

In this study, we seek to understand and to correlate the genetic patterns observed in the population of the island of Ibiza in the Western Mediterranean basin with past events. Genome-wide genotypes of 189 samples representing 13 of 17 regions in Spain have been analyzed, in addition to 105 samples from the Levant, 157 samples from North Africa, and one ancient sample from the Phoenician Cas Molí site in Ibiza. Before the Catalans conquered the island in 1235 CE, Ibiza (Eivissa) had already been influenced by several cultures, starting with the Phoenicians, then the Carthaginians, followed by the Umayyads. The impact of these various cultures on the genetic structure of the islanders is still unexplored. Our results show a clear distinction between Ibiza and the rest of Spain. To investigate whether this was due to the Phoenician colonization or to more recent events, we compared the genomes of current Ibizans to that of an ancient Phoenician sample from Ibiza and to both modern Levantine and North African genomes. We did not identify any trace of Phoenician ancestry in the current Ibizans. Interestingly, the analysis of runs of homozygosity and changes in the effective population size through time support the idea that drift has shaped the genetic structure of current Ibizans. In addition to the small carrying capacity of the island, Ibiza experienced a series of dramatic demographic changes due to several instances of famine, war, malaria and plague that could have significantly contributed to its current genetic differentiation.
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http://dx.doi.org/10.1038/s41431-019-0361-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777470PMC
June 2019

Ancient DNA of Phoenician remains indicates discontinuity in the settlement history of Ibiza.

Sci Rep 2018 12 4;8(1):17567. Epub 2018 Dec 4.

Department of Anatomy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.

Ibiza was permanently settled around the 7 century BCE by founders arriving from west Phoenicia. The founding population grew significantly and reached its height during the 4 century BCE. We obtained nine complete mitochondrial genomes from skeletal remains from two Punic necropoli in Ibiza and a Bronze Age site from Formentara. We also obtained low coverage (0.47X average depth) of the genome of one individual, directly dated to 361-178 cal BCE, from the Cas Molí site on Ibiza. We analysed and compared ancient DNA results with 18 new mitochondrial genomes from modern Ibizans to determine the ancestry of the founders of Ibiza. The mitochondrial results indicate a predominantly recent European maternal ancestry for the current Ibizan population while the whole genome data suggest a significant Eastern Mediterranean component. Our mitochondrial results suggest a genetic discontinuity between the early Phoenician settlers and the island's modern inhabitants. Our data, while limited, suggest that the Eastern or North African influence in the Punic population of Ibiza was primarily male dominated.
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http://dx.doi.org/10.1038/s41598-018-35667-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279797PMC
December 2018

Sequence diversity of the Rh blood group system in Basques.

Eur J Hum Genet 2018 12 8;26(12):1859-1866. Epub 2018 Aug 8.

Institute of Evolutionary Biology (CSIC - UPF), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.

Basques show specific cultural, demographic, and genetic characteristics that have placed them as an isolated and unique population within Europe, such as their non-Indo-European language, Euskara. They have historically lived along the Western Pyrenees, between Spain and France, in one of the most important European glacial refugia during the Last Glacial Maximum. The most striking genetic characteristic is their highest frequency of the RhD blood group negative allele, a variant related to the hemolytic disease of the newborn. Both demographic and adaptive processes have been suggested as possible causes of the high frequency of RhD negative in Basques, but neither hypothesis has been clearly demonstrated. While previous studies on the Rh system in Basques have been mostly focused on serological and genotyping diversity, in this work we analyze genotyping and next generation sequencing data in order to provide a general framework of the genetic scenario of the system in Basques. In particular, we genotyped the most relevant variants of the system (D/d, E/e, and C/c), and sequenced three ~6 kb flanking regions surrounding the Rh genes in Basques and also in other populations for comparison. Our results are in agreement with previous studies, with Basques presenting the highest frequency of the RHD deletion (47.2%). Haplotype analyses of D/d, E/e, and C/c variants confirmed an association between the RhC allele, previously suggested to be under positive selection, and the RhD positive variant in non-sub-Saharan populations, including Basques. We also found extreme differentiation for the C/c variant when comparing sub-Saharan to non-sub-Saharan populations.
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http://dx.doi.org/10.1038/s41431-018-0232-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244411PMC
December 2018

The genetic landscape of Mediterranean North African populations through complete mtDNA sequences.

Ann Hum Biol 2018 Feb;45(1):98-104

a Departament de Ciències Experimentals i de la Salut, Institute of Evolutionary Biology (CSIC-UPF) , Universitat Pompeu Fabra , Barcelona , Spain.

Background: The genetic composition of human North African populations is an amalgam of different ancestral components coming from the Middle East, Europe, south-Saharan Africa and autochthonous to North Africa. This complex genetic pattern is the result of migrations and admixtures in the region since Palaeolithic times.

Aims: The objective of the present study is to refine knowledge of the population history of North African populations through the analysis of complete mitochondrial sequences.

Subjects And Methods: This study has sequenced complete mitochondrial DNAs (mtDNAs) in several North African and neighbouring individuals.

Results: The mtDNA haplogroup classification and phylogeny shows a high genetic diversity in the region as a result of continuous admixture. The phylogenetic analysis allowed us to identify a new haplogroup characterised by positions 10 101 C and 146 C (H1v2), a sub-branch of H1v, which is restricted to North Africa and whose origins are estimated as ∼4000 years ago.

Conclusions: The analysis of the complete mtDNA genome has allowed for the identification of a North African sub-lineage that might be ignored by the analysis of partial mtDNA control region sequences, highlighting the phylogeographic relevance of mtDNA complete sequence analysis.
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http://dx.doi.org/10.1080/03014460.2017.1413133DOI Listing
February 2018

The black legend on the Spanish presence in the low countries: Verifying shared beliefs on genetic ancestry.

Am J Phys Anthropol 2018 05 11;166(1):219-227. Epub 2018 Jan 11.

Early Modern History (15th-18th Centuries), Faculty of Arts, KU Leuven, Leuven, Belgium.

Objectives: War atrocities committed by the Spanish army in the Low Countries during the 16th century are so ingrained in the collective memory of Belgian and Dutch societies that they generally assume a signature of this history to be present in their genetic ancestry. Historians claim this assumption is a consequence of the so-called "Black Legend" and negative propaganda portraying and remembering Spanish soldiers as extreme sexual aggressors. The impact of the presence of Spaniards during the Dutch Revolt on the genetic variation in the Low Countries has been verified in this study.

Materials And Methods: A recent population genetic analysis of Iberian-associated Y-chromosomal variation among Europe is enlarged with representative samples of Dutch (N = 250) and Flemish (N = 1,087) males. Frequencies of these variants are also compared between donors whose oldest reported paternal ancestors lived in-nowadays Flemish-cities affected by so-called Spanish Furies (N = 116) versus other patrilineages in current Flemish territory (N = 971).

Results: The frequencies of Y-chromosomal markers Z195 and SRY2627 decline steeply going north from Spain and the data for the Flemish and Dutch populations fits within this pattern. No trend of higher frequencies of these variants has been found within the well-ascertained samples associated with Spanish Fury cities.

Discussion: Although sexual aggression did occur in the 16th century, these activities did not leave a traceable "Spanish" genetic signature in the autochthonous genome of the Low Countries. Our results support the view that the 'Black Legend' and historical propaganda on sexual aggression have nurtured today's incorrect assumptions regarding genetic ancestry.
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http://dx.doi.org/10.1002/ajpa.23409DOI Listing
May 2018

Whole Y-chromosome sequences reveal an extremely recent origin of the most common North African paternal lineage E-M183 (M81).

Sci Rep 2017 11 21;7(1):15941. Epub 2017 Nov 21.

Institute of Evolutionary Biology (CSIC-UPF), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.

E-M183 (E-M81) is the most frequent paternal lineage in North Africa and thus it must be considered to explore past historical and demographical processes. Here, by using whole Y chromosome sequences from 32 North African individuals, we have identified five new branches within E-M183. The validation of these variants in more than 200 North African samples, from which we also have information of 13 Y-STRs, has revealed a strong resemblance among E-M183 Y-STR haplotypes that pointed to a rapid expansion of this haplogroup. Moreover, for the first time, by using both SNP and STR data, we have provided updated estimates of the times-to-the-most-recent-common-ancestor (TMRCA) for E-M183, which evidenced an extremely recent origin of this haplogroup (2,000-3,000 ya). Our results also showed a lack of population structure within the E-M183 branch, which could be explained by the recent and rapid expansion of this haplogroup. In spite of a reduction in STR heterozygosity towards the West, which would point to an origin in the Near East, ancient DNA evidence together with our TMRCA estimates point to a local origin of E-M183 in NW Africa.
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http://dx.doi.org/10.1038/s41598-017-16271-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698413PMC
November 2017

Analysis of the R1b-DF27 haplogroup shows that a large fraction of Iberian Y-chromosome lineages originated recently in situ.

Sci Rep 2017 08 4;7(1):7341. Epub 2017 Aug 4.

Institut de Biologia Evolutiva (CSIC-UPF), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.

Haplogroup R1b-M269 comprises most Western European Y chromosomes; of its main branches, R1b-DF27 is by far the least known, and it appears to be highly prevalent only in Iberia. We have genotyped 1072 R1b-DF27 chromosomes for six additional SNPs and 17 Y-STRs in population samples from Spain, Portugal and France in order to further characterize this lineage and, in particular, to ascertain the time and place where it originated, as well as its subsequent dynamics. We found that R1b-DF27 is present in frequencies ~40% in Iberian populations and up to 70% in Basques, but it drops quickly to 6-20% in France. Overall, the age of R1b-DF27 is estimated at ~4,200 years ago, at the transition between the Neolithic and the Bronze Age, when the Y chromosome landscape of W Europe was thoroughly remodeled. In spite of its high frequency in Basques, Y-STR internal diversity of R1b-DF27 is lower there, and results in more recent age estimates; NE Iberia is the most likely place of origin of DF27. Subhaplogroup frequencies within R1b-DF27 are geographically structured, and show domains that are reminiscent of the pre-Roman Celtic/Iberian division, or of the medieval Christian kingdoms.
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http://dx.doi.org/10.1038/s41598-017-07710-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544771PMC
August 2017

Length and repeat-sequence variation in 58 STRs and 94 SNPs in two Spanish populations.

Forensic Sci Int Genet 2017 09 16;30:66-70. Epub 2017 Jun 16.

Institut de Biologia Evolutiva (UPF-CSIC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain. Electronic address:

We have genotyped the 58 STRs (27 autosomal, 24 Y-STRs and 7 X-STRs) and 94 autosomal SNPs in Illumina ForenSeq™ Primer Mix A in 88 Spanish Roma (Gypsy) samples and 143 Catalans. Since this platform is based in massive parallel sequencing, we have used simple R scripts to uncover the sequence variation in the repeat region. Thus, we have found, across 58 STRs, 541 length-based alleles, which, after considering repeat-sequence variation, became 804 different alleles. All loci in both populations were in Hardy-Weinberg equilibrium. F between both populations was 0.0178 for autosomal SNPs, 0.0146 for autosomal STRs, 0.0101 for X-STRs and 0.1866 for Y-STRs. Combined a priori statistics showed quite large; for instance, pooling all the autosomal loci, the a priori probabilities of discriminating a suspect become 1-(2.3×10) and 1-(5.9×10), for Roma and Catalans respectively, and the chances of excluding a false father in a trio are 1-(2.6×10) and 1-(2.0×10).
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http://dx.doi.org/10.1016/j.fsigen.2017.06.006DOI Listing
September 2017

The unexpected co-occurrence of GRN and MAPT p.A152T in Basque families: Clinical and pathological characteristics.

PLoS One 2017 8;12(6):e0178093. Epub 2017 Jun 8.

Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, United States of America.

Background: The co-occurrence of the c.709-1G>A GRN mutation and the p.A152T MAPT variant has been identified in 18 Basque families affected by frontotemporal dementia (FTD). We aimed to investigate the influence of the p.A152T MAPT variant on the clinical and neuropathological features of these Basque GRN families.

Methods And Findings: We compared clinical characteristics of 14 patients who carried the c.709-1G>A GRN mutation (GRN+/A152T-) with 21 patients who carried both the c.709-1G>A GRN mutation and the p.A152T MAPT variant (GRN+/A152T+). Neuropsychological data (n = 17) and plasma progranulin levels (n = 23) were compared between groups, and 7 subjects underwent neuropathological studies. We genotyped six short tandem repeat markers in the two largest families. By the analysis of linkage disequilibrium decay in the haplotype block we estimated the time when the first ancestor to carry both genetic variants emerged. GRN+/A152T+ and GRN+/A152T- patients shared similar clinical and neuropsychological features and plasma progranulin levels. All were diagnosed with an FTD disorder, including behavioral variant FTD or non fluent / agrammatic variant primary progressive aphasia, and shared a similar pattern of neuropsychological deficits, predominantly in executive function, memory, and language. All seven participants with available brain autopsies (6 GRN+/A152T+, 1 GRN+/A152T-) showed frontotemporal lobar degeneration with TDP-43 inclusions (type A classification), which is characteristic of GRN carriers. Additionally, all seven showed mild to moderate tau inclusion burden: five cases lacked β-amyloid pathology and two cases had Alzheimer's pathology. The co-occurrence of both genes within one individual is recent, with the birth of the first GRN+/A152T+ individual estimated to be within the last 50 generations (95% probability).

Conclusions: In our sample, the p.A152T MAPT variant does not appear to show a discernible influence on the clinical phenotype of GRN carriers. Whether p.A152T confers a greater than expected propensity for tau pathology in these GRN carriers remains an open question.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178093PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464560PMC
September 2017

Y-chromosomal sequences of diverse Indian populations and the ancestry of the Andamanese.

Hum Genet 2017 05 25;136(5):499-510. Epub 2017 Apr 25.

Institute of Evolutionary Biology (CSIC-UPF), Universitat Pompeu Fabra, Doctor Aiguader 88 (PRBB), 08003, Barcelona, Catalonia, Spain.

We present 42 new Y-chromosomal sequences from diverse Indian tribal and non-tribal populations, including the Jarawa and Onge from the Andaman Islands, which are analysed within a calibrated Y-chromosomal phylogeny incorporating South Asian (in total 305 individuals) and worldwide (in total 1286 individuals) data from the 1000 Genomes Project. In contrast to the more ancient ancestry in the South than in the North that has been claimed, we detected very similar coalescence times within Northern and Southern non-tribal Indian populations. A closest neighbour analysis in the phylogeny showed that Indian populations have an affinity towards Southern European populations and that the time of divergence from these populations substantially predated the Indo-European migration into India, probably reflecting ancient shared ancestry rather than the Indo-European migration, which had little effect on Indian male lineages. Among the tribal populations, the Birhor (Austro-Asiatic-speaking) and Irula (Dravidian-speaking) are the nearest neighbours of South Asian non-tribal populations, with a common origin in the last few millennia. In contrast, the Riang (Tibeto-Burman-speaking) and Andamanese have their nearest neighbour lineages in East Asia. The Jarawa and Onge shared haplogroup D lineages with each other within the last ~7000 years, but had diverged from Japanese haplogroup D Y-chromosomes ~53000 years ago, most likely by a split from a shared ancestral population. This analysis suggests that Indian populations have complex ancestry which cannot be explained by a single expansion model.
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http://dx.doi.org/10.1007/s00439-017-1800-0DOI Listing
May 2017

Satisfaction With Methadone and Opioid Receptor Genes Polymorphisms in Treatment-Refractory Heroin-Dependent Patients.

J Clin Psychopharmacol 2017 06;37(3):378-380

Addictive Behaviors Unit, Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona and Departament de Psiquiatria i Medicina Legal, Universitat Autonoma de Barcelona, Bellaterra and CIBER de Salud Mental, Madrid, Spain. Addictive Behaviors Unit, Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain; Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain; Addictive Behaviors Unit, Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona and CIBER de Salud Mental, Madrid, Spain; Addictive Behaviors Unit, Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona, Spain; Institut de Biologia Evolutiva (CSIC-UPF), Barcelona, Spain; Addictive Behaviors Unit, Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Barcelona and CIBER de Salud Mental, Madrid, Spain; Genetics Department, Hospital de la Santa Creu i Sant Pau and Centre for Biomedical Network Research on Rare Diseases (CIBERER)Barcelona, Spain.

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http://dx.doi.org/10.1097/JCP.0000000000000698DOI Listing
June 2017

Characterization of the Iberian Y chromosome haplogroup R-DF27 in Northern Spain.

Forensic Sci Int Genet 2017 03 29;27:142-148. Epub 2016 Dec 29.

BIOMICs Research Group, Lascaray Research Center, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain. Electronic address:

The European paternal lineage R-DF27 has been proposed as a haplogroup of Iberian origin due to its maximum frequencies in the Iberian Peninsula. In this study, the distribution and structure of DF27 were characterized in 591 unrelated male individuals from four key populations of the north area of the Iberian Peninsula through the analysis of 12 Y-SNPs that define DF27 main sublineages. Additionally, Y-SNP allele frequencies were also gathered from the reference populations in the 1000 Genomes Project to compare and obtain a better landscape of the distribution of DF27. Our results reveal frequencies over 35% of DF27 haplogroup in the four North Iberian populations analyzed and high frequencies for its subhaplogroups. Considering the low frequency of DF27 and its sublineages in most populations outside of the Iberian Peninsula, this haplogroup seems to have geographical significance; thus, indicating a possible Iberian patrilineal origin of vestiges bearing this haplogroup. The dataset presented here contributes with new data to better understand the complex genetic variability of the Y chromosome in the Iberian Peninsula, that can be applied in Forensic Genetics.
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http://dx.doi.org/10.1016/j.fsigen.2016.12.013DOI Listing
March 2017

The Y chromosome as the most popular marker in genetic genealogy benefits interdisciplinary research.

Hum Genet 2017 05 5;136(5):559-573. Epub 2016 Nov 5.

Forensic Biomedical Sciences, Department of Imaging & Pathology, KU Leuven-Catholic University of Leuven, Kapucijnenvoer 33, Leuven, B-3000, Belgium.

The Y chromosome is currently by far the most popular marker in genetic genealogy that combines genetic data and family history. This popularity is based on its haploid character and its close association with the patrilineage and paternal inherited surname. Other markers have not been found (yet) to overrule this status due to the low sensitivity and precision of autosomal DNA for genetic genealogical applications, given the vagaries of recombination, and the lower capacities of mitochondrial DNA combined with an in general much lower interest in maternal lineages. The current knowledge about the Y chromosome and the availability of markers with divergent mutation rates make it possible to answer questions on relatedness levels which differ in time depth; from the individual and familial level to the surnames, clan and population level. The use of the Y chromosome in genetic genealogy has led to applications in several well-established research disciplines; namely in, e.g., family history, demography, anthropology, forensic sciences, population genetics and sex chromosome evolution. The information obtained from analysing this chromosome is not only interesting for academic scientists but also for the huge and lively community of amateur genealogists and citizen-scientists, fascinated in analysing their own genealogy or surname. This popularity, however, has also some drawbacks, mainly for privacy reasons related to the DNA donor, his close family and far-related namesakes. In this review paper we argue why Y-chromosomal analysis and its genetic genealogical applications will still perform an important role in future interdisciplinary research.
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http://dx.doi.org/10.1007/s00439-016-1740-0DOI Listing
May 2017

An assessment of a massively parallel sequencing approach for the identification of individuals from mass graves of the Spanish Civil War (1936-1939).

Electrophoresis 2016 10 5;37(21):2841-2847. Epub 2016 Sep 5.

Genomics Core Facility, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Catalonia, Spain.

Next-generation sequencing technologies have opened new opportunities in forensic genetics. Here, we assess the applicability and performance of the MiSeq FGx™ & ForenSeq™ DNA Signature Prep Kit (Illumina) for the identification of individuals from the mass graves of the Spanish Civil War (1936-1939). The main limitations for individual identification are the low number of possible first-degree living relatives and the high levels of DNA degradation reported in previous studies. Massively parallel sequencing technologies enabling the analysis of hundreds of regions and prioritizing short length amplicons constitute a promising tool for this kind of approaches. In this study, we first explore the power of this new technology to detect first- and second-degree kinship given different scenarios of DNA degradation. Second, we specifically assess its performance in a set of low DNA input samples previously analyzed with CE technologies. We conclude that this methodology will allow identification of up to second-degree relatives, even in situations with low sequencing performance and important levels of allele drop-out; it is thus a technology that resolves previous drawbacks and that will allow a successful approximation to the identification of remains.
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http://dx.doi.org/10.1002/elps.201600180DOI Listing
October 2016

Signatures of Evolutionary Adaptation in Quantitative Trait Loci Influencing Trace Element Homeostasis in Liver.

Mol Biol Evol 2016 Mar 17;33(3):738-54. Epub 2015 Nov 17.

Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain

Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health and disease, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 single nucleotide polymorphism (SNPs) in the same sample set. We detected significant associations for 8 protein quantitative trait loci (pQTL), 10 expression quantitative trait loci (eQTLs), and 15 micronutrient quantitative trait loci (nutriQTL). Six of these exceeded the false discovery rate cutoff and were related to essential trace elements: 1) one pQTL for GPX2 (rs10133290); 2) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and 3) three nutriQTLs: The pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1, GPX3, SLC30A9, and SLC39A8. Overall, this detailed study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients.
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http://dx.doi.org/10.1093/molbev/msv267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760079PMC
March 2016

Genetic Heterogeneity in Algerian Human Populations.

PLoS One 2015 24;10(9):e0138453. Epub 2015 Sep 24.

Institut de Biologia Evolutiva (CSIC-UPF), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Doctor Aiguader 88, 08003 Barcelona, Spain.

The demographic history of human populations in North Africa has been characterized by complex processes of admixture and isolation that have modeled its current gene pool. Diverse genetic ancestral components with different origins (autochthonous, European, Middle Eastern, and sub-Saharan) and genetic heterogeneity in the region have been described. In this complex genetic landscape, Algeria, the largest country in Africa, has been poorly covered, with most of the studies using a single Algerian sample. In order to evaluate the genetic heterogeneity of Algeria, Y-chromosome, mtDNA and autosomal genome-wide makers have been analyzed in several Berber- and Arab-speaking groups. Our results show that the genetic heterogeneity found in Algeria is not correlated with geography or linguistics, challenging the idea of Berber groups being genetically isolated and Arab groups open to gene flow. In addition, we have found that external sources of gene flow into North Africa have been carried more often by females than males, while the North African autochthonous component is more frequent in paternally transmitted genome regions. Our results highlight the different demographic history revealed by different markers and urge to be cautious when deriving general conclusions from partial genomic information or from single samples as representatives of the total population of a region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138453PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581715PMC
June 2016

No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

PLoS One 2015 17;10(9):e0135983. Epub 2015 Sep 17.

Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.

While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135983PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574704PMC
May 2016

Combined epigenetic and intraspecific variation of the DRD4 and SERT genes influence novelty seeking behavior in great tit Parus major.

Epigenetics 2015 1;10(6):516-25. Epub 2015 May 1.

a Evolutionary Ecology Associate Research Unit (CSIC); Natural History Museum of Barcelona ; Barcelona , Spain.

DNA methylation is one of the main epigenetic mechanisms that can regulate gene expression and is an important means for creating phenotypic variation. In the present study, we performed methylation profiling of 2 candidate genes for personality traits, namely DRD4 and SERT, in the great tit Parus major to ascertain whether personality traits and behavior within different habitats have evolved with the aid of epigenetic variation. We applied bisulphite PCR and strand-specific sequencing to determine the methylation profile of the CpG dinucleotides in the DRD4 and SERT promoters and also in the CpG island overlapping DRD4 exon 3. Furthermore, we performed pyrosequencing to quantify the total methylation levels at each CpG location. Our results indicated that methylation was ∼1-4% higher in urban than in forest birds, for all loci and tissues analyzed, suggesting that this epigenetic modification is influenced by environmental conditions. Screening of genomic DNA sequence revealed that the SERT promoter is CpG poor region. The methylation at a single CpG dinucleotide located 288 bp from the transcription start site was related to exploration score in urban birds. In addition, the genotypes of the SERT polymorphism SNP234 located within the minimal promoter were significantly correlated with novelty seeking behavior in captivity, with the allele increasing this behavior being more frequent in urban birds. As a conclusion, it seems that both genetic and methylation variability of the SERT gene have an important role in shaping personality traits in great tits, whereas genetic and methylation variation at the DRD4 gene is not strongly involved in behavior and personality traits.
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http://dx.doi.org/10.1080/15592294.2015.1046027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622863PMC
March 2016

Y-chromosome diversity in Catalan surname samples: insights into surname origin and frequency.

Eur J Hum Genet 2015 Nov 18;23(11):1549-57. Epub 2015 Feb 18.

Departament de Ciències Experimentals i de la Salut, Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), Universitat Pompeu Fabra, CEXS-UPF-PRBB, Barcelona, Catalonia, Spain.

The biological behavior of the Y chromosome, which is paternally inherited, implies that males sharing the same surname may also share a similar Y chromosome. However, socio-cultural factors, such as polyphyletism, non-paternity, adoption, or matrilineal surname transmission, may prevent the joint transmission of the surname and the Y chromosome. By genotyping 17 Y-STRs and 68 SNPs in ~2500 male samples that each carried one of the 50 selected Catalan surnames, we could determine sets of descendants of a common ancestor, the population of origin of the common ancestor, and the date when such a common ancestor lived. Haplotype diversity was positively correlated with surname frequency, that is, rarer surnames showed the strongest signals of coancestry. Introgression rates of Y chromosomes into a surname by non-paternity, adoption, and transmission of the maternal surname were estimated at 1.5-2.6% per generation, with some local variation. Average ages for the founders of the surnames were estimated at ~500 years, suggesting a delay between the origin of surnames (twelfth and thirteenth centuries) and the systematization of their paternal transmission. We have found that, in general, a foreign etymology for a surname does not often result in a non-indigenous origin of surname founders; however, bearers of some surnames with an Arabic etymology show an excess of North African haplotypes. Finally, we estimate that surname prediction from a Y-chromosome haplotype, which may have interesting forensic applications, has a ~60% sensitivity but a 17% false discovery rate.
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http://dx.doi.org/10.1038/ejhg.2015.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613475PMC
November 2015
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