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Background: The cline of human genetic diversity observable across Europe is recapitulated at a micro-geographic scale by variation within the Italian population. Besides resulting from extensive gene flow, this might be ascribable also to local adaptations to diverse ecological contexts evolved by people who anciently spread along the Italian Peninsula. Dissecting the evolutionary history of the ancestors of present-day Italians may thus improve the understanding of demographic and biological processes that contributed to shape the gene pool of European populations. However, previous SNP array-based studies failed to investigate the full spectrum of Italian variation, generally neglecting low-frequency genetic variants and examining a limited set of small effect size alleles, which may represent important determinants of population structure and complex adaptive traits. To overcome these issues, we analyzed 38 high-coverage whole-genome sequences representative of population clusters at the opposite ends of the cline of Italian variation, along with a large panel of modern and ancient Euro-Mediterranean genomes. Results: We provided evidence for the early divergence of Italian groups dating back to the Late Glacial and for Neolithic and distinct Bronze Age migrations having further differentiated their gene pools. We inferred adaptive evolution at insulin-related loci in people from Italian regions with a temperate climate, while possible adaptations to pathogens and ultraviolet radiation were observed in Mediterranean Italians. Some of these adaptive events may also have secondarily modulated population disease or longevity predisposition. Conclusions: We disentangled the contribution of multiple migratory and adaptive events in shaping the heterogeneous Italian genomic background, which exemplify population dynamics and gene-environment interactions that played significant roles also in the formation of the Continental and Southern European genomic landscapes. [ABSTRACT FROM AUTHOR]

Natural epigenetic diversity has been suggested as a key mechanism in microevolutionary processes due to its capability to create phenotypic variability within individuals and populations. It constitutes an important reservoir of variation potentially useful for rapid adaptation in response to environmental stimuli. The analysis of population epigenetic structure represents a possible tool to study human adaptation and to identify external factors that are able to naturally shape human DNA methylation variability. The aim of this study is to investigate the dynamics that create epigenetic diversity between and within different human groups. To this end, we first used publicly available epigenome-wide data to explore population-specific DNA methylation changes that occur at macro-geographic scales. Results from this analysis suggest that nutrients, UVA exposure and pathogens load might represent the main environmental factors able to shape DNA methylation profiles. Then, we evaluated DNA methylation of candidate genes (KRTCAP3, MAD1L1, and BRSK2), emerged from the previous analysis, in individuals belonging to different populations from Morocco, Nigeria, Philippines, China, and Italy, but living in the same Italian city. DNA methylation of the BRSK2 gene is significantly different between Moroccans and Nigerians (pairwise t-test: CpG 6 P-value = 5.2*10-3; CpG 9 P-value = 2.6*10-3; CpG 10 P-value = 3.1*10-3; CpG 11 P-value = 2.8*10-3). Comprehensively, these results suggest that DNA methylation diversity is a source of variability in human groups at macro and microgeographical scales and that population demographic and adaptive histories, as well as the individual ancestry, actually influence DNA methylation profiles. [ABSTRACT FROM AUTHOR]

Objective: Although genetic variants related to lactase persistence in European populations were supposed to have firstly undergone positive selection in farmers from the Balkans and Central Europe, demographic and evolutionary dynamics that subsequently shaped the distribution of this adaptive trait across the continent have still to be elucidated. To deepen the knowledge about potential routes of diffusion of lactase persistence to Western Europe we investigated variation at a large genomic region surrounding the LCT gene along the Italian peninsula, a geographical area that played a key role in population movements responsible for Neolithic diffusion across Europe. Methods: By genotyping 40 highly selected SNPs in more than 400 Italian individuals we described gradients of nucleotide and haplotype variation potentially related to lactase persistence and compared them with those observed in several European and Mediterranean human groups. Results: Multiple migratory events responsible for earlier introduction of the examined alleles in Italy than in Northern European regions could be invoked. Different demic processes occurred along the western and eastern sides of the peninsula were also inferred via linkage disequilibrium and population structure analyses. Conclusion: The appreciable genetic continuum observed between people from Northern or Central-Western Italy and Central European populations suggested a local arrival of lactase persistence-related variants mainly via overland routes. On the contrary, diversity of Central-Eastern and Southern Italian groups entailed also gene flow from South-Eastern Mediterranean regions, in accordance to the earlier entrance of the Neolithic in Southern Italy via maritime population movements along the Mediterranean coastlines. [ABSTRACT FROM AUTHOR]

The human genome is constantly subjected to evolutionary forces which shape its architecture. Insertions of mitochondrial DNA sequences into nuclear genome (NumtS) have been described in several eukaryotic species, including Homo sapiens and other primates. The ongoing process of the generation of NumtS has made them valuable markers in primate phylogenetic studies, as well as potentially informative loci for reconstructing the genetic history of modern humans. Here, we report the identification of 53 human-specific NumtS by inspection of the UCSC genome browser, showing that they may be direct insertions of mitochondrial DNA into the human nuclear DNA after the human-chimpanzee split. In silico analyses allowed us to identify 14 NumtS which are polymorphic in terms of their presence/absence within the human genome in individuals of different ancestry. The allele frequencies of these polymorphic NumtS were calculated for 1000 Genomes Project sequence data from 13 populations worldwide, and principal components analysis and hierarchical clustering methods allowed the detection of strong signals of geographical structure related to the genetic diversity of these loci. All identified polymorphic human-specific NumtS together with a tandemly duplicated NumtS have also been validated by PCR amplification on a panel of 60 samples belonging to five native populations worldwide, confirming the expected NumtS variability. On the basis of these findings, we have succeeded in depicting the landscape of variation of a series of NumtS in several ethnic groups, making an advance in their identification as useful markers in the study on human population genetics. [ABSTRACT FROM AUTHOR]

Abstract: Little is known about alterations of cyclin dependent kinase inhibitors p15INK4B, p16INK4A and of MDM2 inhibitor p14ARF due to single nucleotide polymorphisms (SNPs) located within the CDKN2A/B genes and/or neighbouring loci. In order to investigate the potential involvement of such common DNA sequence variants in leukemia susceptibility, an association study was performed by genotyping 23 SNPs spanning the MTAP, CDKN2A/B and CDKN2BAS loci, as well as relative intergenic regions, in a case-control cohort made up of 149 leukemia patients, including Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) samples, and 183 healthy controls. rs564398, mapping to the CDKN2BAS locus that encodes for ANRIL antisense non-coding RNA, showed a statistically significant correlation with the ALL phenotype, with a risk pattern that was compatible with an overdominant model of disease susceptibility and a OR of 2 (95% CI, 1.20–3.33; p =7.1×10−3). We hypothesized that this association reflects the capability of some ANRIL polymorphisms to contribute to its transcription changes responsible for alterations of CDKN2A/B expression profiles, thus leading to abnormal proliferative boosts and consequent increased ALL susceptibility. [Copyright &y& Elsevier]

It is well established that several Homo sapiens populations experienced admixture with extinct human species during their evolutionary history. Sometimes, such a gene flow could have played a role in modulating their capability to cope with a variety of selective pressures, thus resulting in archaic adaptive introgression events. A paradigmatic example of this evolutionary mechanism is offered by the EPAS1 gene, whose most frequent haplotype in Himalayan highlanders was proved to reduce their susceptibility to chronic mountain sickness and to be introduced in the gene pool of their ancestors by admixture with Denisovans. In this study, we aimed at further expanding the investigation of the impact of archaic introgression on more complex adaptive responses to hypobaric hypoxia evolved by populations of Tibetan/Sherpa ancestry, which have been plausibly mediated by soft selective sweeps and/or polygenic adaptations rather than by hard selective sweeps. For this purpose, we used a combination of composite-likelihood and gene network-based methods to detect adaptive loci in introgressed chromosomal segments from Tibetan WGS data and to shortlist those presenting Denisovan-like derived alleles that participate to the same functional pathways and are absent in populations of African ancestry, which are supposed to do not have experienced Denisovan admixture. According to this approach, we identified multiple genes putatively involved in archaic introgression events and that, especially as regards TBC1D1, RASGRF2, PRKAG2, and KRAS, have plausibly contributed to shape the adaptive modulation of angiogenesis and of certain cardiovascular traits in high-altitude Himalayan peoples. These findings provided unprecedented evidence about the complexity of the adaptive phenotype evolved by these human groups to cope with challenges imposed by hypobaric hypoxia, offering new insights into the tangled interplay of genetic determinants that mediates the physiological adjustments crucial for human adaptation to the high-altitude environment. [ABSTRACT FROM AUTHOR]

Human longevity is a complex phenotype resulting from the combinations of context-dependent gene-environment interactions that require analysis as a dynamic process in a cohesive ecological and evolutionary framework. Genome-wide association (GWAS) and whole-genome sequencing (WGS) studies on centenarians pointed toward the inclusion of the apolipoprotein E (APOE) polymorphisms ε2 and ε4, as implicated in the attainment of extreme longevity, which refers to their effect in age-related Alzheimer's disease (AD) and cardiovascular disease (CVD). In this case, the available literature on APOE and its involvement in longevity is described according to an anthropological and population genetics perspective. This aims to highlight the evolutionary history of this gene, how its participation in several biological pathways relates to human longevity, and which evolutionary dynamics may have shaped the distribution of APOE haplotypes across the globe. Its potential adaptive role will be described along with implications for the study of longevity in different human groups. This review also presents an updated overview of the worldwide distribution of APOE alleles based on modern day data from public databases and ancient DNA samples retrieved from literature in the attempt to understand the spatial and temporal frame in which present-day patterns of APOE variation evolved. [ABSTRACT FROM AUTHOR]

Several studies demonstrated that populations living in the Tibetan plateau are genetically and physiologically adapted to high-altitude conditions, showing genomic signatures ascribable to the action of natural selection. However, so far most of them relied solely on inferences drawn from the analysis of coding variants and point mutations. To fill this gap, we focused on the possible role of polymorphic transposable elements in influencing the adaptation of Tibetan and Sherpa highlanders. To do so, we compared high-altitude and middle/low-lander individuals of East Asian ancestry by performing in silico analyses and differentiation tests on 118 modern and ancient samples. We detected several transposable elements associated with high altitude, which map genes involved in cardiovascular, hematological, chem-dependent and respiratory conditions, suggesting that metabolic and signaling pathways taking part in these functions are disproportionately impacted by the effect of environmental stressors in high-altitude individuals. To our knowledge, our study is the first hinting to a possible role of transposable elements in the adaptation of Tibetan and Sherpa highlanders. • Tibetan and Sherpa groups are physiologically adapted to high-altitude environments. • We analyzed 118 high-coverage genomes from high-, middle- and low- altitude populations of East Asia and Africa. • Polymorphic transposable elements (TEs) are useful for detecting signatures of differentiation and population structure. • Polymorphic TEs possibly contributed to differentiation and adaptation of Tibetan and Sherpa highlanders. [ABSTRACT FROM AUTHOR]

Objective Frequency patterns of the lactase persistence (LP)-associated −13,915 G allele and archaeological records pointing to substantial role played by southern regions in the peopling and domestication processes that involved the Arabian Peninsula suggest that Southern Arabia plausibly represented the center of diffusion of such adaptive variant. Nevertheless, a well-defined scenario for evolution of Arabian LP is still to be elucidated and the burgeoning archaeological picture of complex human migrations occurred through the peninsula is not matched by an equivalent high-resolution description of genetic variation underlying this adaptive trait. To fill this gap, we investigated diversity at a wide genomic interval surrounding the LCT gene in different Southern Arabian populations. Methods 40 SNPs were genotyped to characterize LCT profiles of 630 Omani and Yemeni individuals to perform population structure, linkage disequilibrium, population differentiation-based and haplotype-based analyses. Results Typical Arabian LP-related variation was found in Dhofaris and Yemenis, being characterized by private haplotypes carrying the −13,915 G allele, unusual differentiation with respect to northern groups and conserved homozygous haplotype-blocks, suggesting that the adaptive allele was likely introduced in the Arabian gene pool in southern populations and was then subjected to prolonged selective pressure. Conclusion By pointing to Yemen as one of the best candidate centers of diffusion of the Arabian-specific adaptive variant, obtained results indicate the spread of indigenous groups as the main process underlying dispersal of LP along the Arabian Peninsula, supporting a refugia model for Arabian demic movements occurred during the Terminal Pleistocene and Early Holocene. [ABSTRACT FROM AUTHOR]

Context: Epigenetics represents a still unexplored research field in the understanding of micro- and macro-evolutionary mechanisms, as epigenetic changes create phenotypic diversity within both individuals and populations. Objective: The purpose of this review is to dissect the landscape of studies focused on DNA methylation, one of the most described epigenetic mechanisms, emphasizing the aspects that could be relevant in human adaptations. Methods: Theories and results here considered were collected from the most recent papers published. Results: The matter of DNA methylation inheritance is here described as well as the recent evolutionary theories regarding the role of DNA methylation-and epigenetics in a broader sense-in human evolution. The complex relation between (1) DNA methylation and genetic variability and (2) DNA methylation and the environmental stimuli crucial in shaping genetic and phenotypic variability through the human lineage-such as diet, climate and pathogens exposure-are described. Papers about population epigenetics are also illustrated due to their high relevance in this context. Conclusion: Genetic, epigenetic and phenotypic variations of the species, together with cultural ones, are considerably shaped by a vast range of environmental stimuli, thus representing the foundation of all human bio-cultural adaptations. [ABSTRACT FROM AUTHOR]

Heiniger, Grégory, Simon Walbaum, Claudio Sartori, Alban Lovis, Marco Sazzini, Andrew Wellman, and Raphael Heinzer. Altitude-Induced Sleep Apnea Is Highly Dependent on Ethnic Background (Sherpa Vs. Tamang). High Alt Med Biol. 23:165–172, 2022. Rationale: High altitude-induced hypocapnic alkalosis generates central sleep apnea (CSA). In Nepal, two ethnic groups live at medium-to-high altitude: Tamangs originate from low-altitude Tibeto-Burman populations, whereas Sherpas descend from high-altitude Tibetans. Objective: To compare apnea severity at low and high altitude between Sherpas and Tamangs. Methods: Polygraphy recordings, including airflow and oxygen saturation, were performed in Nepal at "low" (2,030 m) and "high" (4,380 m) altitudes. Resting ventilation ( V ̇ E ) and mixed-exhaled CO2 (FECO2) were also measured at the same altitudes. Differences in apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and % of nocturnal periodic breathing (NPB) at the two altitudes were compared between ethnicities. Measurements and Main Results: Twenty Sherpas and 20 Tamangs were included (males, median [interquartile range] age: 24.5 [21.5–27.8] years vs. 26.0 [21.5–39.8] years, body mass index: 23.9 [22.1–26.1] kg/m2 vs. 25.21 [20.6–27.6] kg/m2). Compared with Tamangs, Sherpas showed a lower increase in AHI (+7.5 [2.6–17.2]/h vs. +31.5 [18.2–57.3]/h, p < 0.001), ODI (+13.8 [5.5–28.2]/h vs. +42.0 [22.6–77.6]/h, p < 0.001), and NPB proportion (+0.9 [0–3.5]% vs. +12.8 [3.1–27.4]%, p < 0.001) from low to high altitude. Resting V ̇ E was higher in Sherpas versus Tamangs at both low (8.45 [6.89–10.70] l/min vs. 6.3 [4.9–8.3] l/min, p = 0.005) and high (9.7 [8.5–11] l/min vs. 8.74 [7.39–9.73] l/min, p = 0.020) altitudes, whereas the mean ± standard deviation FECO2 decrease between low and high altitude was greater in Tamangs versus Sherpas (−0.50% ± 0.44% vs. −0.80% ± 0.33%, p < 0.023). Conclusion: Overall, altitude-adapted Sherpas showed a 3.2-times smaller increase in sleep-disordered breathing between low and high altitude compared with Tamangs, and higher ventilation and a smaller drop in FECO2 at high altitude. These data suggest that genetic differences in breathing control can be protective against CSA. [ABSTRACT FROM AUTHOR]

Background: Imputation is a statistical process used to predict genotypes of loci not directly assayed in a sample of individuals. Our goal is to measure the performance of imputation in predicting the genotype of the best known gene polymorphisms involved in drug metabolism using a common SNP array genotyping platform generally exploited in genome wide association studies. Methods: Thirty-nine (39) individuals were genotyped with both Affymetrix Genome Wide Human SNP 6.0 (AFFY) and Affymetrix DMET Plus (DMET) platforms. AFFY and DMET contain nearly 900000 and 1931 markers respectively. We used a 1000 Genomes Pilot + HapMap 3 reference panel. Imputation was performed using the computer program Impute, version 2. SNPs contained in DMET, but not imputed, were analysed studying markers around their chromosome regions. The efficacy of the imputation was measured evaluating the number of successfully imputed SNPs (SSNPs). Results: The imputation predicted the genotypes of 654 SNPs not present in the AFFY array, but contained in the DMET array. Approximately 1000 SNPs were not annotated in the reference panel and therefore they could not be directly imputed. After testing three different imputed genotype calling threshold (IGCT), we observed that imputation performs at its best for IGCT value equal to 50%, with rate of SSNPs (MAF > 0.05) equal to 85%. Conclusions: Most of the genes involved in drug metabolism can be imputed with high efficacy using standard genome-wide genotyping platforms and imputing procedures. [ABSTRACT FROM AUTHOR]

Background: The Arbereshe are an Albanian-speaking ethno-linguistic minority who settled in Calabria (southern Italy) about five centuries ago. Aim: This study aims to clarify the genetic relationships between Italy and the Balkans through analysis of Y-chromosome variability in a peculiar case study, the Arbereshe. Subject and methods: Founder surnames were used as a means to identify a sample of individuals that might trace back to the Albanians at the time of their establishment in Italy. These results were compared with data of more than 1000 individuals from Italy and the Balkans. Results: The distributions of haplogroups (defined using 31 UEPs) and haplotypes (12 STRs) show that the Italian and Balkan populations are clearly divergent from each other. Within this genetic landscape, the Arbereshe are characterized by two peculiarities: (a) they are a clear outlier in the Italian genetic background, showing a strong genetic affinity with southern Balkans populations; and (b) they retain a high degree of genetic diversity. Conclusion: These results support the hypothesis that the surname-chosen Arbereshe are representative of the Y-chromosome genetic variability of the Albanian founder population. Accordingly, the Arbereshe genetic structure can contribute to the interpretation of the recent biological history of the southern Balkans. Intra-haplogroup analyses suggest that this area may have experienced important changes in the last five centuries, resulting in a marked increase in the frequency of haplogroups I2a and J2. [ABSTRACT FROM AUTHOR]

Calabrian Greeks are an enigmatic population that have preserved and evolved a unique variety of language, Greco, survived in the isolated Aspromonte mountain area of Southern Italy. To understand their genetic ancestry and explore possible effects of geographic and cultural isolation, we genome-wide genotyped a large set of South Italian samples including both communities that still speak Greco nowadays and those that lost the use of this language earlier in time. Comparisons with modern and ancient populations highlighted ancient, long-lasting genetic links with Eastern Mediterranean and Caucasian/Near-Eastern groups as ancestral sources of Southern Italians. Our results suggest that the Aspromonte communities might be interpreted as genetically drifted remnants that departed from such ancient genetic background as a consequence of long-term isolation. Specific patterns of population structuring and higher levels of genetic drift were indeed observed in these populations, reflecting geographic isolation amplified by cultural differences in the groups that still conserve the Greco language. Isolation and drift also affected the current genetic differentiation at specific gene pathways, prompting for future genome-wide association studies aimed at exploring trait-related loci that have drifted up in frequency in these isolated groups. [ABSTRACT FROM AUTHOR]

Adoption of diets based on some cereals, especially on rice, signified an iconic change in nutritional habits for many Asian populations and a relevant challenge for their capability to maintain glucose homeostasis. Indeed, rice shows the highest carbohydrates content and glycemic index among the domesticated cereals and its usual ingestion represents a potential risk factor for developing insulin resistance and related metabolic diseases. Nevertheless, type 2 diabetes and obesity epidemiological patterns differ among Asian populations that rely on rice as a staple food, with higher diabetes prevalence and increased levels of central adiposity observed in people of South Asian ancestry rather than in East Asians. This may be at least partly due to the fact that populations from East Asian regions where wild rice or other cereals such as millet have been already consumed before their cultivation and/or were early domesticated have relied on these nutritional resources for a period long enough to have possibly evolved biological adaptations that counteract their detrimental side effects. To test such a hypothesis, we compared adaptive evolution of these populations with that of control groups from regions where the adoption of cereal‐based diets occurred many thousand years later and which were identified from a genome‐wide dataset including 2,379 individuals from 124 East Asian and South Asian populations. This revealed selective sweeps and polygenic adaptive mechanisms affecting functional pathways involved in fatty acids metabolism, cholesterol/triglycerides biosynthesis from carbohydrates, regulation of glucose homeostasis, and production of retinoic acid in Chinese Han and Tujia ethnic groups, as well as in people of Korean and Japanese ancestry. Accordingly, long‐standing rice‐ and/or millet‐based diets have possibly contributed to trigger the evolution of such biological adaptations, which might represent one of the factors that play a role in mitigating the metabolic risk of these East Asian populations. [ABSTRACT FROM AUTHOR]

Objectives: The Yaghnobis are an ethno‐linguistic minority historically settled along the Yaghnob River in the Upper‐Zarafshan Valley in Tajikistan. They speak a language of Old Sogdian origin, which is the only present‐day witness of the Lingua Franca used along the Silk Road in Late Antiquity. The aim of this study was to reconstruct the genetic history of this community in order to shed light on its isolation and genetic ancestry within the Euro‐Asiatic context. Materials and Methods: A total of 100 DNA samples were collected in the Yaghnob and Matcha Valleys during several expeditions and their mitochondrial, Y‐chromosome and autosomal genome‐wide variation were compared with that from a large set of modern and ancient Euro‐Asiatic samples. Results: Findings from uniparental markers highlighted the long‐term isolation of the Yaghnobis. Mitochondrial DNA ancestry traced an ancient link with Middle Eastern populations, whereas Y‐chromosome legacy showed more tight relationships with Central Asians. Admixture, outgroup‐f3, and D‐statistics computed on autosomal variation corroborated Y‐chromosome evidence, pointing respectively to low Anatolian Neolithic and high Steppe ancestry proportions in Yaghnobis, and to their closer affinity with Tajiks than to Iranians. Discussion: Although the Yaghnobis do not show evident signs of recent admixture, they could be considered a modern proxy for the source of gene flow for many Central Asian and Middle Eastern groups. Accordingly, they seem to retain a peculiar genomic ancestry probably ascribable to an ancient gene pool originally wide spread across a vast area and subsequently reshuffled by distinct demographic events occurred in Middle East and Central Asia. [ABSTRACT FROM AUTHOR]

Investigation of human mitochondrial DNA variation patterns and phylogeny has been extensively used in Anthropological and Population Genetics studies and sequencing the whole mitochondrial genome is progressively becoming the gold standard. Among the currently available massive parallel sequencing technologies, Ion Torrent™ semiconductor sequencing represents a promising approach for such studies. Nevertheless, an experimental protocol conceived to enable the achievement of both as high as possible yield and of the most homogeneous sequence coverage through the whole mitochondrial genome is still not available. The present work was thus aimed at improving the overall performance of whole mitochondrial genomes Ion Torrent™ sequencing, with special focus on the capability to obtain robust coverage and highly reliable variants calling. For this purpose, a series of cost-effective modifications in standard laboratory workflows was fine-tuned to optimize them for medium- and large-scale population studies. A total of 54 human samples were thus subjected to sequencing of the whole mitochondrial genome with the Ion Personal Genome Machine™ System in four distinct experiments and using Ion 314 chips. Seven of the selected samples were also characterized by means of conventional Sanger sequencing for the sake of comparison. Obtained results demonstrated that the implemented optimizations had definitely improved sequencing outputs in terms of both variants calling efficiency and coverage uniformity, enabling to setup an effective and accurate protocol for whole mitochondrial genome sequencing and a considerable reduction in experimental time consumption and sequencing costs. [ABSTRACT FROM PUBLISHER]

Observable patterns of cultural variation are consistently intertwined with demic movements, cultural diffusion, and adaptation to different ecological contexts [Cavalli-Sforza and Feldman (1981) Cultural Transmission and Evolution: A Quantitative Approach; Boyd and Richerson (1985) Culture and the Evolutionary Process]. The quantitative study of gene–culture coevolution has focused in particular on the mechanisms responsible for change in frequency and attributes of cultural traits, the spread of cultural information through demic and cultural diffusion, and detecting relationships between genetic and cultural lineages. Here, we make use of worldwide whole-genome sequences [Pagani et al. (2016) Nature 538:238–242] to assess the impact of processes involving population movement and replacement on cultural diversity, focusing on the variability observed in folktale traditions (n = 596) [Uther (2004) The Types of International Folktales: A Classification and Bibliography. Based on the System of Antti Aarne and Stith Thompson] in Eurasia. We find that a model of cultural diffusion predicted by isolation-by-distance alone is not sufficient to explain the observed patterns, especially at small spatial scales (up to ∼4,000 km). We also provide an empirical approach to infer presence and impact of ethnolinguistic barriers preventing the unbiased transmission of both genetic and cultural information. After correcting for the effect of ethnolinguistic boundaries, we show that, of the alternative models that we propose, the one entailing cultural diffusion biased by linguistic differences is the most plausible. Additionally, we identify 15 tales that are more likely to be predominantly transmitted through population movement and replacement and locate putative focal areas for a set of tales that are spread worldwide. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Current methods to determine chronological age from modern and ancient remains rely on both morphological and molecular approaches. However, low accuracy and the lack of standardized protocols make the development of alternative methods for the estimation of individual's age even more urgent for several research fields, such as biological anthropology, biodemography, forensics, evolutionary genetics, and ancient DNA studies. Therefore, the aim of this study is to identify genomic regions whose DNA methylation level correlates with age in modern teeth. Methods We used MALDI-TOF mass spectrometry to analyze DNA methylation levels of specific CpGs located in the ELOVL2, FHL2, and PENK genes. We considered methylation data from cementum, dentin and pulp of 21 modern teeth (from 17 to 77 years old) to construct a mathematical model able to exploit DNA methylation values to predict age of the individuals. Results The median difference between the real age and that estimated using DNA methylation values is 1.20 years (SD = 1.9) if DNA is recovered from both cementum and pulp of the same modern teeth, 2.25 years (SD = 2.5) if DNA is recovered from dental pulp, 2.45 years (SD = 3.3) if DNA is extracted from cementum and 7.07 years (SD = 7.0) when DNA is recovered from dentin only. Discussion We propose for the first time the evaluation of DNA methylation at ELOVL2, FHL2, and PENK genes as a powerful tool to predict age in modern teeth for anthropological applications. Future studies are needed to apply this method also to historical and relatively ancient human teeth. Am J Phys Anthropol 159:585-595, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Genetic signatures from the Paleolithic inhabitants of Eurasia can be traced from the early divergent mitochondrial DNA lineages still present in contemporary human populations. Previous studies already suggested a pre-Neolithic diffusion of mitochondrial haplogroup HV*(xH,V) lineages, a relatively rare class of mtDNA types that includes parallel branches mainly distributed across Europe and West Asia with a certain degree of structure. Up till now, variation within haplogroup HV was addressed mainly by analyzing sequence data from the mtDNA control region, except for specific sub-branches, such as HV4 or the widely distributed haplogroups H and V. In this study, we present a revised HV topology based on full mtDNA genome data, and we include a comprehensive dataset consisting of 316 complete mtDNA sequences including 60 new samples from the Italian peninsula, a previously underrepresented geographic area. We highlight points of instability in the particular topology of this haplogroup, reconstructed with BEAST-generated trees and networks. We also confirm a major lineage expansion that probably followed the Late Glacial Maximum and preceded Neolithic population movements. We finally observe that Italy harbors a reservoir of mtDNA diversity, with deep-rooting HV lineages often related to sequences present in the Caucasus and the Middle East. The resulting hypothesis of a glacial refugium in Southern Italy has implications for the understanding of late Paleolithic population movements and is discussed within the archaeological cultural shifts occurred over the entire continent. [ABSTRACT FROM AUTHOR]

To investigate the genetic variability of IL- 17A, IL17- RA, IL- 23A and IL- 23R genes on an in-depth phenotypically characterized northern Italian Psoriatic arthritis (PsA) case-control cohort, in search for associations specific to different PsA clinical sub-phenotypes. We examined 118 patients with PsA according to CASPAR criteria (mean age 57 ± 13, female 38.4 %, mean disease duration 13.9 ± 8.6 years, peripheral disease 83.8 %, axial manifestations 34.5 %, radiological erosive disease 49 %) compared with 248 controls of the same ethnic origin matched for age and sex. The presence of axial disease was defined by the clinical axial involvement and/or the presence of radiological alteration consistent with spondyloarthropathy according to New York criteria. The presence of peripheral disease (arthritis and/or enthesitis) was defined only on clinical basis. A total of 40 SNPs, mapping within the genes mentioned above, were genotyped in both groups and used to perform association analyses by subdividing the PsA sample into subgroups according to different clinical manifestations on the basis of axial and peripheral involvements. No differences between patients and controls were found in the distribution of the IL- 17A, IL17- RA, IL- 23A and IL- 23R genes allelic variants. Comparing patients with axial disease versus those without, we found that axial manifestations were significantly associated with the presence of IL-23R rs12401432 GG homozygosity (26.8 % vs. 5.3 %, p = 0.019, OR 2.63 [95 % CI 1.13-6.16]). No differences in distribution of the allelic variants were found comparing patients with versus those without peripheral disease or patients with versus without radiological peripheral erosions. In PA patients of northern Italian origin, IL- 17A, IL17- RA, IL- 23A and IL- 23R genes allelic variants are not associated with disease susceptibility. However, a strong association with the IL- 23RA rs12401432 GG genotype is associated with axial involvement of the disease. [ABSTRACT FROM AUTHOR]

East Africa (EA) has witnessed pivotal steps in the history of human evolution. Due to its high environmental and cultural variability, and to the long-term human presence there, the genetic structure of modern EA populations is one of the most complicated puzzles in human diversity worldwide. Similarly, the widespread Afro-Asiatic (AA) linguistic phylum reaches its highest levels of internal differentiation in EA. To disentangle this complex ethno-linguistic pattern, we studied mtDNA variability in 1,671 individuals (452 of which were newly typed) from 30 EA populations and compared our data with those from 40 populations (2970 individuals) from Central and Northern Africa and the Levant, affiliated to the AA phylum. The genetic structure of the studied populations-explored using spatial Principal Component Analysis and Model-based clustering-turned out to be composed of four clusters, each with different geographic distribution and/or linguistic affiliation, and signaling different population events in the history of the region. One cluster is widespread in Ethiopia, where it is associated with different AA-speaking populations, and shows shared ancestry with Semitic-speaking groups from Yemen and Egypt and AA-Chadic-speaking groups from Central Africa. Two clusters included populations from Southern Ethiopia, Kenya and Tanzania. Despite high and recent gene-flow (Bantu, Nilo-Saharan pastoralists), one of them is associated with a more ancient AA-Cushitic stratum. Most North-African and Levantine populations (AA-Berber, AA-Semitic) were grouped in a fourth and more differentiated cluster. We therefore conclude that EA genetic variability, although heavily influenced by migration processes, conserves traces of more ancient strata. Am J Phys Anthropol, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This paper explores the genetic structure and signatures of natural selection in different sub-populations from the Island of Sardinia, exploiting information from nearly 700 000 autosomal SNPs genotyped with the Affymetrix Genome-Wide Human SNP 6.0 Array. The genetic structure of the Sardinian population and its position within the context of other Mediterranean and European human groups were investigated in depth by comparing our data with publicly available data sets. Principal components and admixture analyses suggest a clustering of the examined samples in two significantly differentiated sub-populations (Ogliastra and Southern Sardinia), as confirmed by AMOVA (FST=0.011; P<0.001). Differentiation of these sub-populations was still evident when they were pooled together with supplementary Sardinian samples from HGDP and compared with several other European, North-African and Near Eastern populations, confirming the uniqueness of the Sardinian genetic background. Moreover, by applying several statistical approaches aimed at assessing differences at the SNP level, the highest differentiated genomic regions between Ogliastra and Southern Sardinia were thus investigated via an extended haplotype homozygosity (EHH)-based test to point out potential selective sweeps. Using this approach, 40 genomic regions were detected, with significant differences between Ogliastra and Southern Sardinia. These regions were subsequently investigated using a long-range haplotype test, which found significant REHH values for SNPs rs11070188 and rs11070192 in the Ogliastra sub-population. In the light of these results and the overlap of the different computed statistics, the region encompassing these loci can be considered a strong candidate to have undergone selective pressure in Ogliastra. [ABSTRACT FROM AUTHOR]

The NBN gene has been included in breast cancer (BC) multigene panels based on early studies suggesting an increased BC risk for carriers, though not confirmed by recent research. To evaluate the impact of NBN analysis, we assessed the results of NBN sequencing in 116 BRCA-negative BC patients and reviewed the literature. Three patients (2.6%) carried potentially relevant variants: two, apparently unrelated, carried the frameshift variant c.156_157delTT and another one the c.628G>T variant. The latter was subsequently found in 4/1390 (0.3%) BC cases and 8/1580 (0.5%) controls in an independent sample, which, together with in silico predictions, provided evidence against its pathogenicity. Conversely, the rare c.156_157delTT variant was absent in the case-control set; moreover, a 50% reduction of NBN expression was demonstrated in one carrier. However, in one family it failed to co-segregate with BC, while the other carrier was found to harbor also a probably pathogenic TP53 variant that may explain her phenotype. Therefore, the c.156_157delTT, although functionally deleterious, was not supported as a cancer-predisposing defect. Pathogenic/likely pathogenic NBN variants were detected by multigene panels in 31/12314 (0.25%) patients included in 15 studies. The risk of misinterpretation of such findings is substantial and supports the exclusion of NBN from multigene panels. [ABSTRACT FROM AUTHOR]

The pathogenesis of idiopathic and heritable forms of pulmonary arterial hypertension is still not completely understood, even though several causative genes have been proposed, so that a third of patients remains genetically unresolved. Here we applied a multistep approach to extend identification of the genetic bases of such a disease by searching for novel candidate genes/pathways. Twenty-eight patients belonging to 18 families were screened for BMPR2 mutations and BMPR2-negative samples were tested for 12 additional candidate genes by means of a specific massive parallel sequencing-based assay. Finally, whole exome sequencing was performed on four patients showing no mutations at known disease genes, as well as on their unaffected parents. In addition to EIF2AK4, which has been already suggested to be associated with pulmonary veno-occlusive disease, we identified the novel candidate genes ATP13A3, CD248, EFCAB4B, involved in lung vascular remodeling that represent reliable drivers contributing to the disease according to their biological functions/inheritance patterns. Therefore, our results suggest that combining gene panel and whole exome sequencing provides new insights useful for the genetic diagnosis of familial and idiopathic pulmonary arterial hypertension, as well as for the identification of biological pathways that will be potentially targeted by new therapeutic strategies. [ABSTRACT FROM AUTHOR]