[Show abstract][Hide abstract] ABSTRACT: This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447-2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8-30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics.
PLoS ONE 10/2015; 10(10):e0140146. DOI:10.1371/journal.pone.0140146 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The animal and plant biodiversity of the Italian territory is known to be one of the
richest in the Mediterranean basin and Europe as a whole, but does the genetic diversity of extant human
populations show a comparable pattern? According to a number of studies, the genetic structure of Italian
populations retains the signatures of complex peopling processes which took place from the Paleolithic to
modern era. Although the observed patterns highlight a remarkable degree of genetic heterogeneity, they do
not, however, take into account an important source of variation. In fact, Italy is home to numerous ethnolinguistic
minorities which have yet to be studied systematically. Due to their difference in geographical
origin and demographic history, such groups not only signal the cultural and social diversity of our country,
but they are also potential contributors to its bio-anthropological heterogeneity. To fill this gap, research
groups from four Italian Universities (Bologna, Cagliari, Pisa and Roma Sapienza) started a collaborative
study in 2007, which was funded by the Italian Ministry of Education, University and Research and
received partial support by the Istituto Italiano di Antropologia. In this paper, we present an account of
the results obtained in the course of this initiative. Four case-studies relative to linguistic minorities from
the Eastern Alps, Sardinia, Apennines and Southern Italy are first described and discussed, focusing on
their micro-evolutionary and anthropological implications. Thereafter, we present the results of a systematic
analysis of the relations between linguistic, geographic and genetic isolation. Integrating the data obtained
in the course of the long-term study with literature and unpublished results on Italian populations, we
show that a combination of linguistic and geographic factors is probably responsible for the presence of the
most robust signatures of genetic isolation. Finally, we evaluate the magnitude of the diversity of Italian
populations in the European context. The human genetic diversity of our country was found to be greater
than observed throughout the continent at short (0-200 km) and intermediate (700-800km) distances, and
accounted for most of the highest values of genetic distances observed at all geographic ranges. Interestingly,
an important contribution to this pattern comes from the “linguistic islands” (e.g. German speaking groups
of Sappada and Luserna from the Eastern Italian Alps), further proof of the importance of considering social
and cultural factors when studying human genetic variation.
Journal of anthropological sciences 12/2014; DOI:10.4436/JASS.92001 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The work makes use of surname analysis, repeated pairs and kinship estimates in 11,009 marriage records celebrated in five communities of the Italian Central Apennine (Celano, Lecce dei Marsi, Ortucchio, Roio, Villavallelonga) from 1802 to 1965 with the objective to deepen knowledge of the relative influence of several determinants on their marital behaviour. These towns are part of the same geographic and economic environment: the slopes of the ancient Fucino Lake. This work further elaborates the results from previous studies on the bio-demographic model of the region. The data were analyzed according to three periods of approximately 50 years. Results show the highest inbreeding coefficients in the pastoral towns of Roio and Villavallelonga. Repeated pair analysis highlights a certain degree of population subdivision which declined in time in Celano, Lecce dei Marsi and Ortucchio. The highest and increasing values of RP-RPr in time in Roio suggest a general reduction in genetic heterogeneity. This is possibly due to the celebration of marriages among families selected on the economic basis of pastoralism, as this town historically has had a leading tradition of sheep-farming. Villavallelonga, excluding isonymous marriages, shows an increase in repeated pair unions in time, thus revealing a substructure with marriages among preferred lineages. This is in line with previous results on consanguineous marriages which indicated the tendency of avoiding unions between close relatives in this small geographic isolate. This study demonstrates the influence of geographical (altitude) and social factors (pastoralism) on the marital structures of the investigated populations.
Homo: internationale Zeitschrift fur die vergleichende Forschung am Menschen 09/2013; 65(1). DOI:10.1016/j.jchb.2013.08.001 · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tat language is classified in an Iranian subbranch of the Indo-European family. It is spoken in the Caucasus and in the West Caspian region by populations with heterogeneous cultural traditions and religion whose ancestry is unknown. The aim of this study is to get a first insight about the genetic history of this peculiar linguistic group.
We investigated the uniparental gene pools, defined by NRY and mtDNA high-resolution markers, in two Tati-speaking communities from Dagestan: Mountain Jews or Juhur, who speak the Judeo-Tat dialect, and the Tats, who speak the Muslim-Tat dialect. The samples have been collected in monoethnic rural villages and selected on the basis of genealogical relationships. A novel approach aimed at resolving cryptic cases in the recent history of human populations, which combines the properties of uniparental genetic markers with the potential of "forward-in-time" computer simulations, is presented.
Judeo-Tats emerged as a group with tight matrilineal genetic legacy who separated early from other Jewish communities. Tats exhibited genetic signals of a much longer in situ evolution, which appear as substantially unlinked with other Indo-Iranian enclaves in the Caucasus.
The independent demographic histories of the two samples, with mutually reversed profiles at paternally and maternally transmitted genetic systems, suggest that geographic proximity and linguistic assimilation of Tati-speakers from Dagestan do not reflect a common ancestry.
American Journal of Human Biology 07/2012; 24(4):391-9. DOI:10.1002/ajhb.22220 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several simulators have been recently developed in the field of evolutionary genetics which make it possible to test empirical data under hypotheses of genetic variation generated by evolutionary causes. In the perspectives opened in the post-genomic era, they need to meet the growing demand for flexible and computationally efficient algorithms capable of managing genome-wide population datasets. Backward and forward-in-time strategies are available when attempting to better understand the complexity of the evolutionary scenarios actually followed by real populations. However, both strategies have a number of pros and cons. Although non recombinant uni-parentally inherited (NRUP) haplotypes, as the variants of the mitochondrial genome and the majority of Y chromosome polymorphisms, have been an invaluable source of genetic information during the last two decades of molecular anthropological research, few dedicated programs have been designed to model their evolution. The present paper is a brief comparative and annotated overview of the simulation tools developed in the field of population genetics which can be applied to large NRUP data in order to test complex hypotheses concerning genetic variation from a human evolutionary perspective.
[Show abstract][Hide abstract] ABSTRACT: We have surveyed 15 high-altitude adaptation candidate genes for signals of positive selection in North Caucasian highlanders using targeted re-sequencing. A total of 49 unrelated Daghestani from three ethnic groups (Avars, Kubachians, and Laks) living in ancient villages located at around 2,000 m above sea level were chosen as the study population. Caucasian (Adygei living at sea level, N = 20) and CEU (CEPH Utah residents with ancestry from northern and western Europe; N = 20) were used as controls. Candidate genes were compared with 20 putatively neutral control regions resequenced in the same individuals. The regions of interest were amplified by long-PCR, pooled according to individual, indexed by adding an eight-nucleotide tag, and sequenced using the Illumina GAII platform. 1,066 SNPs were called using false discovery and false negative thresholds of ~6%. The neutral regions provided an empirical null distribution to compare with the candidate genes for signals of selection. Two genes stood out. In Laks, a non-synonymous variant within HIF1A already known to be associated with improvement in oxygen metabolism was rediscovered, and in Kubachians a cluster of 13 SNPs located in a conserved intronic region within EGLN1 showing high population differentiation was found. These variants illustrate both the common pathways of adaptation to high altitude in different populations and features specific to the Daghestani populations, showing how even a mildly hypoxic environment can lead to genetic adaptation.
Electronic supplementary material
The online version of this article (doi:10.1007/s00439-011-1084-8) contains supplementary material, which is available to authorized users.
Human Genetics 09/2011; 131(3):423-33. DOI:10.1007/s00439-011-1084-8 · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A (CA)n repeat located in the 3' UTR region of exon 29 of the NOS1 gene (encoding for neuronal nitric oxide synthase) has been shown to affect the size of mRNA. NOS1 mRNA is highly diverse, contributing to changes in transcript generation, degradation, processing, or subcellular targeting. In the present work, we analyzed allele frequencies of this (CA)n repeat in nine populations of the Mediterranean area and Middle Europe. We aimed at testing the presence of a north-south positive gradient of frequencies of ≤17 allele repeats, compatible with the hypothesis of positive selection suggested in two of our previous works, related to the past prevalence of malaria infection in Europe.
Results show significant negative correlations of latitude with frequencies of alleles S and genotypes S/S and S/L (p < 0.01).
In conclusion, the north-south gradient of S alleles found in the present work would confirm our previous observation about the NOS1 gene, reinforcing the hypothesis of a selective action of malaria infection. This hypothesis is strengthened by the role of nitric oxide in the immunity system.
[Show abstract][Hide abstract] ABSTRACT: Y chromosome variation at 12 STR (the Powerplex® Y system core set) and 18 binary markers was investigated in two major (the Ghegs and the Tosks) and two minor (the Gabels and the Jevgs) populations from Albania (Southern Balkans). The large proportion of haplotypes shared within and between groups makes the Powerplex 12-locus set inadequate to ensure a suitable power of discrimination for the forensic practice. At least 85% of Y lineages in the Jevgs, the cultural minority claiming an Egyptian descent, turned out to be of either Roma or Balkan ancestry. They also showed unequivocal signs of a common genetic history with the Gabels, the other Albanian minority practising social and cultural Roma traditions.
Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 03/2010; 124(5):363-70. DOI:10.1007/s00414-010-0432-x · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Detection of genes that have been targeted by natural selection is a powerful tool for predicting regions of the genome potentially linked with diseases and of interest in the field of genetic epidemiology. In recent years, several methods to detect patterns of natural selection have been developed. In general, these tests are based on different assumptions and parameters; hence, the detection of outlier loci with more than one statistical approach simultaneously will support the candidate status of a particular locus. In this study, we evaluated the presence of patterns of positive selection in 17 short tandem repeat loci genotyped in six different human populations from the Mediterranean area, for a total of 429 individuals. To identify patterns of selective pressure, we applied three different neutrality tests on the basis of different models, performing pairwise comparisons between populations. Results show the presence of one marker, a (CA)n repeat located in exon 29 of the NOS1 gene, which seems significant in the three different tests in two pairwise comparisons: Sicily vs Morocco and Balearic Islands vs Morocco. This suggests that this locus and its genome localization are candidates for further studies to investigate selective pressure, as well as for association studies.
Journal of Human Genetics 02/2010; 55(4):207-14. DOI:10.1038/jhg.2010.7 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Caucasus region is a complex cultural and ethnic mosaic, comprising populations that speak Caucasian, Indo-European and Altaic languages. Isolated mountain villages (auls) in Dagestan still preserve high level of genetic and cultural diversity and have patriarchal societies with a long history of isolation. The aim of this study was to understand the genetic history of five Dagestan highland auls with distinct ethnic affiliation (Avars, Chechens-Akkins, Kubachians, Laks, Tabasarans) using markers on the male-specific region of the Y chromosome. The groups analyzed here are all Muslims but speak different languages all belonging to the Nakh-Dagestanian linguistic family. The results show that the Dagestan ethnic groups share a common Y-genetic background, with deep-rooted genealogies and rare alleles, dating back to an early phase in the post-glacial recolonization of Europe. Geography and stochastic factors, such as founder effect and long-term genetic drift, driven by the rigid structuring of societies in groups of patrilineal descent, most likely acted as mutually reinforcing key factors in determining the high degree of Y-genetic divergence among these ethnic groups.
Journal of Human Genetics 11/2009; 54(12):689-94. DOI:10.1038/jhg.2009.94 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we report the genetic variation of autosomal and Y-chromosomal microsatellites in a large Cameroon population dataset (a total of 11 populations) and jointly analyze novel and previous genetic data (mitochondrial DNA and protein coding loci) taking geographic and cultural factors into consideration. The complex pattern of genetic variation of Cameroon can in part be described by contrasting two geographic areas (corresponding to the northern and southern part of the country), which differ substantially in environmental, biological, and cultural aspects. Northern Cameroon populations show a greater within- and among-group diversity, a finding that reflects the complex migratory patterns and the linguistic heterogeneity of this area. A striking reduction of Y-chromosomal genetic diversity was observed in some populations of the northern part of the country (Podokwo and Uldeme), a result that seems to be related to their demographic history rather than to sampling issues. By exploring patterns of genetic, geographic, and linguistic variation, we detect a preferential correlation between genetics and geography for mtDNA. This finding could reflect a female matrimonial mobility that is less constrained by linguistic factors than in males. Finally, we apply the island model to mitochondrial and Y-chromosomal data and obtain a female-to-male migration Nnu ratio that was more than double in the northern part of the country. The combined effect of the propensity to inter-populational admixture of females, favored by cultural contacts, and of genetic drift acting on Y-chromosomal diversity could account for the peculiar genetic pattern observed in northern Cameroon.
American Journal of Physical Anthropology 11/2009; 140(3):454-64. DOI:10.1002/ajpa.21088 · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we report novel data on mitochondrial DNA in two of the largest eastern Bantu-speaking populations, the Shona from Zimbabwe and the Hutu from Rwanda. The goal is to evaluate the genetic relationships of these two ethnic groups with other Bantu-speaking populations. Moreover, by comparing our data with those from other Niger-Congo speaking populations, we aim to clarify some aspects of evolutionary and demographic processes accompanying the spread of Bantu languages in sub-Saharan Africa and to test if patterns of genetic variation fit with models of population expansion based on linguistic and archeological data. The results indicate that the Shona and Hutu are closely related to the other Bantu-speaking populations. However, there are some differences in haplogroup composition between the two populations, mainly due to different genetic contributions from neighboring populations. This result is confirmed by estimates of migration rates which show high levels of gene flow not only between pairs of Bantu-speaking populations, but also between Bantu and non-Bantu speakers. The observed pattern of genetic variability (high genetic homogeneity and high levels of gene flow) supports a linguistic model suggesting a gradual spread of Bantu-speakers, with strong interactions between the different lines of Bantu-speaker descent, and is also in agreement with recent archeological findings. In conclusion, our data emphasize the role that population admixture has played at different times and to varying degrees in the dispersal of Bantu languages.
American Journal of Physical Anthropology 10/2009; 140(2):302-11. DOI:10.1002/ajpa.21070 · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Malagasy have been shown to be a genetically admixed population combining parental lineages with African and South East Asian ancestry. In the present paper, we fit the Malagasy admixture history in a highly resolved phylogeographic framework by typing a large set of mitochondrial DNA and Y DNA markers in unrelated individuals from inland (Merina) and coastal (Antandroy, Antanosy, and Antaisaka) ethnic groups. This allowed performance of a multilevel analysis in which the diversity among main ethnic divisions, lineage ancestries, and modes of inheritance could be concurrently evaluated. Admixture was confirmed to result from the encounter of African and Southeast Asian people with minor recent male contributions from Europe. However, new scenarios are depicted about Malagasy admixture history. The distribution of ancestral components was ethnic and sex biased, with the Asian ancestry appearing more conserved in the female than in the male gene pool and in inland than in coastal groups. A statistic based on haplotype sharing (D(HS)), showing low sampling error and time linearity over the last 200 generations, was introduced here for the first time and helped to integrate our results with linguistic and archeological data. The focus about the origin of Malagasy lineages was enlarged in space and pushed back in time. Homelands could not be pinpointed but appeared to comprise two vast areas containing different populations from sub-Saharan Africa and South East Asia. The pattern of diffusion of uniparental lineages was compatible with at least two events: a primary admixture of proto-Malay people with Bantu speakers bearing a western-like pool of haplotypes, followed by a secondary flow of Southeastern Bantu speakers unpaired for gender (mainly male driven) and geography (mainly coastal).
[Show abstract][Hide abstract] ABSTRACT: The origin of the Etruscans (the present day Tuscany, Italy), one of the most enigmatic non-Indo-European civilizations, is under intense controversy. We found novel genetic evidences on the mitochondrial DNA (mtDNA) establishing a genetic link between Anatolia and the ancient Etruria. By way of complete mtDNA genome sequencing of a novel autochthonous Tuscan branch of haplogroup U7 (namely U7a2a), we have estimated an historical time frame for the arrival of Anatolian lineages to Tuscany ranging from 1.1+/-0.1 to 2.3+/-0.4 kya B.P.
European journal of human genetics: EJHG 05/2009; 17(5):693-6. DOI:10.1038/ejhg.2008.224 · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present day distribution of Y chromosomes bearing the haplogroup J1 M267(*)G variant has been associated with different episodes of human demographic history, the main one being the diffusion of Islam since the Early Middle Ages. To better understand the modes and timing of J1 dispersals, we reconstructed the genealogical relationships among 282 M267(*)G chromosomes from 29 populations typed at 20 YSTRs and 6 SNPs. Phylogenetic analyses depicted a new genetic background consistent with climate-driven demographic dynamics occurring during two key phases of human pre-history: (1) the spatial expansion of hunter gatherers in response to the end of the late Pleistocene cooling phases and (2) the displacement of groups of foragers/herders following the mid-Holocene rainfall retreats across the Sahara and Arabia. Furthermore, J1 STR motifs previously used to trace Arab or Jewish ancestries were shown unsuitable as diagnostic markers for ethnicity.
European journal of human genetics: EJHG 05/2009; 17(11):1520-4. DOI:10.1038/ejhg.2009.58 · 4.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mediterranean red-legged (Alectoris rufa) and rock (Alectoris graeca) partridge populations are affected by genetic pollution. The chukar partridge (Alectoris chukar), a species only partly native to Europe, is the most frequently introgressive taxon detected in the genome of hybrid partridges.
Both theoretical (evolutionary) and practical (resources management) matters spur to get insight into the geographic origin
of the A. chukar hybridizing swarm. The phenotypic A. rufa populations colonizing the easternmost part of the distribution range of this species, the islands of Elba (Italy) and Corsica
(France), were investigated. The analysis of both mitochondrial (mtDNA: Cytochrome-b gene plus Control Region: 2,250 characters) and nuclear (Short Tandem Repeats, STR; Random Amplified Polymorphic DNA, RAPD)
genomes of 25 wild (Elba) and 20 captive (Corsica) partridges, disclosed spread introgression of chukar origin also in these
populations. All mtDNA haplotypes of Elba and Corsica partridges along with those we obtained from other A. rufa (total, n=111: Italy, Spain, France) and A. graeca (n=6, Italy), were compared with the mtDNA haplotypes of chukars (n=205) sampled in 20 countries. It was found that the A. chukar genes detected in red-legged (n=43) and rock partridges (n=4) of Spain, France and Italy as well as in either introduced (Italy) or native (Greece, Turkey) chukars (n=35) were all from East Asia. Hence, a well-defined geographic origin of the exotic chukar genes polluting the genome of
native Mediterranean A. rufa and A. graeca (inter-specific level) as well as A. chukar (intra-specific level), was demonstrated.
[Show abstract][Hide abstract] ABSTRACT: The present work attempts to determine the distribution of CYP11A (TTTTA)n genotype and allele frequencies in 10 European and North African populations. This polymorphism has been associated with hyperandrogenism by several association studies. To our knowledge, this is the first study investigating the ethnic variation of this polymorphism. DNA was extracted from 868 whole-blood samples with the standard phenol-chloroform technique, and PCR reactions were carried out using fluorescent primers as described previously. PCR products were analyzed by an ABI 3,730 DNA Analyzer. A total of six alleles were identified, ranging from 220 bp (4 repeats [4R]) to 250 bp (10R). The most frequent allelic fragment size in all populations was 4R, with frequencies ranging from 47.9% (Sicily) to 62.8% (Tuscany and Germany). Allelic frequencies showed high heterogeneity between analyzed populations. We detected a significant gradient for alleles 4R and 8R. In this study, we report the allele frequency distribution of CYP11A (TTTTA)n showing a north-south geographic gradient. This result could be useful for epidemiological studies about hyperandrogenism.
[Show abstract][Hide abstract] ABSTRACT: We briefly review the current status of anthropological and genetic studies of isolated populations and of their micro-evolutionary and biomedical applications, with particular emphasis on European populations. Thereafter, we describe the ongoing collaborative research project "Isolating the Isolates: geographic and cultural factors of human genetic variation" regarding Italian extant geographical and/or linguistic isolates, aimed at overcoming the limitations of previous studies regarding geographical coverage of isolates, number and type of genetic polymorphisms under study and suitability of the experimental design to investigate gene-culture coevolutionary processes. An interdisciplinary sampling approach will make it possible to collect several linguistic isolates and their geographic neighbours from Trentino, Veneto, Friuli, Tuscany, Sardinia and Calabria. This will be coupled with a shared genotyping strategy based on mitochondrial and Y-chromosomal polymorphisms. The results will be analyzed with a focus on the role of geographical and cultural factors in shaping human biodiversity. The aims of the project go beyond the simple reconstruction of the genetic structure and history of the examined groups. In fact, the study will also include an assessment for future bio-medical studies and the development of genetic and bio-demographic databases. Ethical and educational aspects are also foreseen by the project, by using informed consents together with disseminating activities in loco, completed by the creation of a dedicated web site for both scientific and public audiences.
Journal of anthropological sciences 01/2008; 86:179-88. · 1.70 Impact Factor