Publications by authors named "Marco Sazzini"

42 Publications

Genomic adaptations to cereal-based diets contribute to mitigate metabolic risk in some human populations of East Asian ancestry.

Evol Appl 2021 Feb 8;14(2):297-313. Epub 2020 Sep 8.

Laboratory of Molecular Anthropology & Centre for Genome Biology Department of Biological, Geological and Environmental Sciences University of Bologna Bologna Italy.

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.
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http://dx.doi.org/10.1111/eva.13090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896717PMC
February 2021

Genetic history of Calabrian Greeks reveals ancient events and long term isolation in the Aspromonte area of Southern Italy.

Sci Rep 2021 Feb 4;11(1):3045. Epub 2021 Feb 4.

Department of Cultural Heritage, University of Bologna, Ravenna, Italy.

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.
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http://dx.doi.org/10.1038/s41598-021-82591-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862261PMC
February 2021

Investigating Mitonuclear Genetic Interactions Through Machine Learning: A Case Study on Cold Adaptation Genes in Human Populations From Different European Climate Regions.

Front Physiol 2020 11;11:575968. Epub 2020 Nov 11.

Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.

Cold climates represent one of the major environmental challenges that anatomically modern humans faced during their dispersal out of Africa. The related adaptive traits have been achieved by modulation of thermogenesis and thermoregulation processes where nuclear (nuc) and mitochondrial (mt) genes play a major role. In human populations, mitonuclear genetic interactions are the result of both the peculiar genetic history of each human group and the different environments they have long occupied. This study aims to investigate mitonuclear genetic interactions by considering all the mitochondrial genes and 28 nuclear genes involved in brown adipose tissue metabolism, which have been previously hypothesized to be crucial for cold adaptation. For this purpose, we focused on three human populations (i.e., Finnish, British, and Central Italian people) of European ancestry from different biogeographical and climatic areas, and we used a machine learning approach to identify relevant nucDNA-mtDNA interactions that characterized each population. The obtained results are twofold: (i) at the methodological level, we demonstrated that a machine learning approach is able to detect patterns of genetic structure among human groups from different latitudes both at single genes and by considering combinations of mtDNA and nucDNA loci; (ii) at the biological level, the analysis identified population-specific nuclear genes and variants that likely play a relevant biological role in association with a mitochondrial gene (such as the "obesity gene" in Finnish people). Further studies are needed to fully elucidate the evolutionary dynamics (e.g., migration, admixture, and/or local adaptation) that shaped these nucDNA-mtDNA interactions and their functional role.
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http://dx.doi.org/10.3389/fphys.2020.575968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686538PMC
November 2020

Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans.

BMC Biol 2020 05 22;18(1):51. Epub 2020 May 22.

Interdepartmental Centre Alma Mater Research Institute on Global Challenges and Climate Change, University of Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1186/s12915-020-00778-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243322PMC
May 2020

Grasping the genetic determinants of human adaptations: the "Kings of the Mountains" (Sherpa) case study.

Authors:
Marco Sazzini

J Anthropol Sci 2019 Dec 20;96:1-7. Epub 2019 Dec 20.

Department of Biological, Geological and Environmental Sciences (BiGeA) Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Italy,

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http://dx.doi.org/10.4436/JASS.97011DOI Listing
December 2019

Gut microbiota composition in Himalayan and Andean populations and its relationship with diet, lifestyle and adaptation to the high-altitude environment.

J Anthropol Sci 2019 Dec 25;96:189-208. Epub 2019 Nov 25.

Institute of Biology and Agrarian Biotechnology (IBBA), National Research Council (CNR), Pisa, Italy,

Human populations living at high altitude evolved a number of biological adjustments to cope with a challenging environment characterised especially by reduced oxygen availability and limited nutritional resources. This condition may also affect their gut microbiota composition. Here, we explored the impact of exposure to such selective pressures on human gut microbiota by considering different ethnic groups living at variable degrees of altitude: the high-altitude Sherpa and low-altitude Tamang populations from Nepal, the high-altitude Aymara population from Bolivia, as well as a low-altitude cohort of European ancestry, used as control. We thus observed microbial profiles common to the Sherpa and Aymara, but absent in the low-altitude cohorts, which may contribute to the achievement of adaptation to high-altitude lifestyle and nutritional conditions. The collected evidences suggest that microbial signatures associated to these rural populations may enhance metabolic functions able to supply essential compounds useful for the host to cope with high altitude-related physiological changes and energy demand. Therefore, these results add another valuable piece of the puzzle to the understanding of the beneficial effects of symbiosis between microbes and their human host even from an evolutionary perspective.
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http://dx.doi.org/10.4436/JASS.97007DOI Listing
December 2019

Dissecting the Pre-Columbian Genomic Ancestry of Native Americans along the Andes-Amazonia Divide.

Mol Biol Evol 2019 06;36(6):1254-1269

Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.

Extensive European and African admixture coupled with loss of Amerindian lineages makes the reconstruction of pre-Columbian history of Native Americans based on present-day genomes extremely challenging. Still open questions remain about the dispersals that occurred throughout the continent after the initial peopling from the Beringia, especially concerning the number and dynamics of diffusions into South America. Indeed, if environmental and historical factors contributed to shape distinct gene pools in the Andes and Amazonia, the origins of this East-West genetic structure and the extension of further interactions between populations residing along this divide are still not well understood. To this end, we generated new high-resolution genome-wide data for 229 individuals representative of one Central and ten South Amerindian ethnic groups from Mexico, Peru, Bolivia, and Argentina. Low levels of European and African admixture in the sampled individuals allowed the application of fine-scale haplotype-based methods and demographic modeling approaches. These analyses revealed highly specific Native American genetic ancestries and great intragroup homogeneity, along with limited traces of gene flow mainly from the Andes into Peruvian Amazonians. Substantial amount of genetic drift differentially experienced by the considered populations underlined distinct patterns of recent inbreeding or prolonged isolation. Overall, our results support the hypothesis that all non-Andean South Americans are compatible with descending from a common lineage, while we found low support for common Mesoamerican ancestors of both Andeans and other South American groups. These findings suggest extensive back-migrations into Central America from non-Andean sources or conceal distinct peopling events into the Southern Continent.
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http://dx.doi.org/10.1093/molbev/msz066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526910PMC
June 2019

The Genetic Variability of in Different Human Populations and Its Implications for Longevity.

Genes (Basel) 2019 03 15;10(3). Epub 2019 Mar 15.

Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, Italy.

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 () 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 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 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 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 variation evolved.
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http://dx.doi.org/10.3390/genes10030222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471373PMC
March 2019

The genetic legacy of the Yaghnobis: A witness of an ancient Eurasian ancestry in the historically reshuffled central Asian gene pool.

Am J Phys Anthropol 2019 04 29;168(4):717-728. Epub 2019 Jan 29.

Laboratories of Physical Anthropology and Ancient DNA, Department of Cultural Heritage, University of Bologna, Ravenna, Italy.

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.
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http://dx.doi.org/10.1002/ajpa.23789DOI Listing
April 2019

A Combined Targeted and Whole Exome Sequencing Approach Identified Novel Candidate Genes Involved in Heritable Pulmonary Arterial Hypertension.

Sci Rep 2019 01 24;9(1):753. Epub 2019 Jan 24.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1038/s41598-018-37277-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345742PMC
January 2019

Aneuploid acute myeloid leukemia exhibits a signature of genomic alterations in the cell cycle and protein degradation machinery.

Cancer 2019 03 27;125(5):712-725. Epub 2018 Nov 27.

Munich Leukemia Laboratory, Munich, Germany.

Background: Aneuploidy occurs in more than 20% of acute myeloid leukemia (AML) cases and correlates with an adverse prognosis.

Methods: To understand the molecular bases of aneuploid acute myeloid leukemia (A-AML), this study examined the genomic profile in 42 A-AML cases and 35 euploid acute myeloid leukemia (E-AML) cases.

Results: A-AML was characterized by increased genomic complexity based on exonic variants (an average of 26 somatic mutations per sample vs 15 for E-AML). The integration of exome, copy number, and gene expression data revealed alterations in genes involved in DNA repair (eg, SLX4IP, RINT1, HINT1, and ATR) and the cell cycle (eg, MCM2, MCM4, MCM5, MCM7, MCM8, MCM10, UBE2C, USP37, CK2, CK3, CK4, BUB1B, NUSAP1, and E2F) in A-AML, which was associated with a 3-gene signature defined by PLK1 and CDC20 upregulation and RAD50 downregulation and with structural or functional silencing of the p53 transcriptional program. Moreover, A-AML was enriched for alterations in the protein ubiquitination and degradation pathway (eg, increased levels of UHRF1 and UBE2C and decreased UBA3 expression), response to reactive oxygen species, energy metabolism, and biosynthetic processes, which may help in facing the unbalanced protein load. E-AML was associated with BCOR/BCORL1 mutations and HOX gene overexpression.

Conclusions: These findings indicate that aneuploidy-related and leukemia-specific alterations cooperate to tolerate an abnormal chromosome number in AML, and they point to the mitotic and protein degradation machineries as potential therapeutic targets.
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http://dx.doi.org/10.1002/cncr.31837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587451PMC
March 2019

Evidence of Polygenic Adaptation to High Altitude from Tibetan and Sherpa Genomes.

Genome Biol Evol 2018 11 1;10(11):2919-2930. Epub 2018 Nov 1.

Laboratory of Molecular Anthropology & Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.

Although Tibetans and Sherpa present several physiological adjustments evolved to cope with selective pressures imposed by the high-altitude environment, especially hypobaric hypoxia, few selective sweeps at a limited number of hypoxia related genes were confirmed by multiple genomic studies. Nevertheless, variants at these loci were found to be associated only with downregulation of the erythropoietic cascade, which represents an indirect aspect of the considered adaptive phenotype. Accordingly, the genetic basis of Tibetan/Sherpa adaptive traits remains to be fully elucidated, in part due to limitations of selection scans implemented so far and mostly relying on the hard sweep model.In order to overcome this issue, we used whole-genome sequence data and several selection statistics as input for gene network analyses aimed at testing for the occurrence of polygenic adaptation in these high-altitude Himalayan populations. Being able to detect also subtle genomic signatures ascribable to weak positive selection at multiple genes of the same functional subnetwork, this approach allowed us to infer adaptive evolution at loci individually showing small effect sizes, but belonging to highly interconnected biological pathways overall involved in angiogenetic processes.Therefore, these findings pinpointed a series of selective events neglected so far, which likely contributed to the augmented tissue blood perfusion observed in Tibetans and Sherpa, thus uncovering the genetic determinants of a key biological mechanism that underlies their adaptation to high altitude.
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http://dx.doi.org/10.1093/gbe/evy233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239493PMC
November 2018

Impact of demography and population dynamics on the genetic architecture of human longevity.

Aging (Albany NY) 2018 Aug;10(8):1947-1963

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.

The study of the genetics of longevity has been mainly addressed by GWASs that considered subjects from different populations to reach higher statistical power. The "price to pay" is that population-specific evolutionary histories and trade-offs were neglected in the investigation of gene-environment interactions. We propose a new "diachronic" approach that considers processes occurred at both evolutionary and lifespan timescales. We focused on a well-characterized population in terms of evolutionary history ( Italians) and we generated genome-wide data for 333 centenarians from the peninsula and 773 geographically-matched healthy individuals. Obtained results showed that: (i) centenarian genomes are enriched for an ancestral component likely shaped by pre-Neolithic migrations; (ii) centenarians born in Northern Italy unexpectedly clustered with controls from Central/Southern Italy suggesting that Neolithic and Bronze Age gene flow did not favor longevity in this population; (iii) local past adaptive events in response to pathogens and targeting arachidonic acid metabolism became favorable for longevity; (iv) lifelong changes in the frequency of several alleles revealed pleiotropy and trade-off mechanisms crucial for longevity. Therefore, we propose that demographic history and ancient/recent population dynamics need to be properly considered to identify genes involved in longevity, which can differ in different temporal/spatial settings.
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http://dx.doi.org/10.18632/aging.101515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128422PMC
August 2018

Three Reportedly Unrelated Families With Liddle Syndrome Inherited From a Common Ancestor.

Hypertension 2018 02 11;71(2):273-279. Epub 2017 Dec 11.

From the Department of Biology (L.P.) and Endocrinology Unit, Department of Medicine (F.M.), University of Padova, Italy; Estonian Biocentre, Tartu (L.P.); Research Department of Genetics, Evolution and Environment, University College London, United Kingdom (Y.D., M.G.T.); Department of Biological Geological and Environmental Sciences (M.S., S.D.F., D.L.) and Department of Experimental, Diagnostic and Specialty Medicine (P.G.), University of Bologna, Italy; IRCCS Centro Cardiologico Monzino, Milano, Italy (M.R.); Department of Oncology and Advanced Technologies, Laboratory of Molecular Biology (E.F., B.C.) and Department of Internal Medicine (E.R.), IRCCS Santa Maria Nuova Hospital, Reggio Emilia, Italy; Department of Endocrinology and Metabolic Diseases, San Raffaele Scientific Institute, Milano, Italy (A.C.); and Department of Molecular Medicine, University of Pavia, Italy (F.N., O.Z.).

Liddle syndrome is considered a rare Mendelian hypertension. We have previously described 3 reportedly unrelated families, native of an Italian area around the Strait of Messina, carrying the same mutation (βP617L) of the epithelial sodium channel. The aims of our study were (1) to evaluate whether a close genomic relationship exists between the 3 families through the analysis of mitochondrial DNA and Y chromosome; and (2) to quantify the genomic relatedness between the patients with Liddle syndrome belonging to the 3 families and assess the hypothesis of a mutation shared through identity by descent. HVRI (the hypervariable region I) of the mitochondrial DNA genome and the Y chromosome short tandem repeats profiles were analyzed in individuals of the 3 families. Genotyping 542 585 genome-wide single nucleotide polymorphisms was performed in all the patients with Liddle syndrome of the 3 families and some of their relatives. A panel of 780 healthy Italian adult samples typed for the same set of markers was used as controls. espite different lineages between the 3 families based on the analysis of mitochondrial DNA and Y chromosome, the 3 probands and their 6 affected relatives share the same ≈5 Mbp long haplotype which encompasses the mutant allele. Using an approach based on coalescent theory, we estimate that the 3 families inherited the mutant allele from a common ancestor ≈13 generations ago and that such an ancestor may have left ≈20 carriers alive today. The prevalence of Liddle syndrome in the region of origin of the 3 families may be much higher than that estimated worldwide.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.117.10491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767121PMC
February 2018

The genomic landscape of Nepalese Tibeto-Burmans reveals new insights into the recent peopling of Southern Himalayas.

Sci Rep 2017 Nov 14;7(1):15512. Epub 2017 Nov 14.

Laboratory of Molecular Anthropology & Centre for Genome Biology, Dept. of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.

While much research attention has focused on demographic processes that enabled human diffusion on the Tibetan plateau, little is known about more recent colonization of Southern Himalayas. In particular, the history of migrations, admixture and/or isolation of populations speaking Tibeto-Burman languages, which is supposed to be quite complex and to have reshaped patterns of genetic variation on both sides of the Himalayan arc, remains only partially elucidated. We thus described the genomic landscape of previously unsurveyed Tibeto-Burman (i.e. Sherpa and Tamang) and Indo-Aryan communities from remote Nepalese valleys. Exploration of their genomic relationships with South/East Asian populations provided evidence for Tibetan admixture with low-altitude East Asians and for Sherpa isolation. We also showed that the other Southern Himalayan Tibeto-Burmans derived East Asian ancestry not from the Tibetan/Sherpa lineage, but from low-altitude ancestors who migrated from China plausibly across Northern India/Myanmar, having experienced extensive admixture that reshuffled the ancestral Tibeto-Burman gene pool. These findings improved the understanding of the impact of gene flow/drift on the evolution of high-altitude Himalayan peoples and shed light on migration events that drove colonization of the southern Himalayan slopes, as well as on the role played by different Tibeto-Burman groups in such a complex demographic scenario.
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http://dx.doi.org/10.1038/s41598-017-15862-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686152PMC
November 2017

Lactase persistence in Tunisia as a result of admixture with other Mediterranean populations.

Genes Nutr 2017 24;12:20. Epub 2017 Aug 24.

Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences (BiGeA), University of Bologna, 40126 Bologna, Italy.

Background: The ability to digest lactose after weaning, namely, lactase persistence (LP), is encoded by polymorphisms in the gene and varies widely in frequency among different human populations. Although, evolution of LP-related genetic variants was investigated in many groups of Sub-Saharan African, Middle Eastern, and European ancestry, only few studies have focused on populations from North Africa and no data are especially available from the Tunisian one. For this reason, there is an urgent need to investigate the frequency patterns at these loci in Tunisia since this adaptive trait is implicated in health.

Methods: Forty SNPs covering the genes and including the two functional variants - 13,910 C > T and - 22,018 G > A were genotyped in 117 Tunisian individuals using the Sequenom Mass Array technology. The observed nucleotide and haplotype patterns of variation were then compared with those of several African, European, and Mediterranean human groups for which comparable data were publicly available. Admixture analysis on a 5 Mb genomic region surrounding the loci was also performed by extracting genotypes from a previously generated genome-wide dataset in order to deepen the reconstruction of the evolutionary history of these loci.

Results: We found that lactase non-persistence (LNP)-related alleles and haplotypes were predominantly present in the examined population. A clear differentiation between Tunisian, African, and North European/North Italian samples was found, while the Tunisian population showed more genetic affinity to Central and South Italian groups.

Conclusions: Our study provided a first report of LP-associated alleles and haplotypes in the Tunisian population. We highlighted a gradient followed by LP diffusion from Europe to North Africa. Based on the rich historic background of Tunisia, we suggest that this adaptive trait was introduced in that geographic region by a relatively recent gene flow.
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http://dx.doi.org/10.1186/s12263-017-0573-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571577PMC
August 2017

Inferring patterns of folktale diffusion using genomic data.

Proc Natl Acad Sci U S A 2017 08 7;114(34):9140-9145. Epub 2017 Aug 7.

Centre for the Coevolution of Biology and Culture, Department of Anthropology, Durham University, DH1 3LE Durham, United Kingdom

Observable patterns of cultural variation are consistently intertwined with demic movements, cultural diffusion, and adaptation to different ecological contexts [Cavalli-Sforza and Feldman (1981) ; Boyd and Richerson (1985) ]. 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) 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 ( = 596) [Uther (2004) ] 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 [Formula: see text]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.
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http://dx.doi.org/10.1073/pnas.1614395114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576778PMC
August 2017

Multiple selective events at the PRDM16 functional pathway shaped adaptation of western European populations to different climate conditions.

J Anthropol Sci 2017 12 10;95:235-247. Epub 2017 Jul 10.

Laboratory of Molecular Anthropology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, 40126, Italy; Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, 40126, Italy.

Several studies highlighted the role of climate in shaping many human evolutionary processes. This occurred even in relatively recent times, having affected various human phenotypic traits, among which metabolic processes that orchestrate absorption and accumulation of substances to maintain energy homeostasis, that is critical for the survival of individuals in high energy-expenditure environments. To date, most researches have focalized on detection of climatic influence on SNPs' frequency in populations exposed to extreme environmental conditions or by comparing variation patterns between populations from different continents. In this study, we instead explored the genetic background of distinct western European human groups at loci involved in nutritional and thermoregulation processes, to test whether patterns of differential local adaptation to environmental conditions could be appreciated also at a lower geographical scale. Taking advantage from the 1000 Genomes Project data, genetic information for 21 genes involved in nutritional and thermoregulation processes was analysed for three western European populations. The applied Anthropological Genetics methods pointed to appreciable differentiation between the examined groups especially for the PRDM16 gene. Moreover, several neutrality tests suggested that balancing selection has acted on different regions of the gene in people from Great Britain, as well as that more recent positive selection could have also targeted some PRDM16 SNPs in Finn and Italian populations. These series of adaptive footprints are plausibly related to climate variability in both ancient and relatively recent times. Since this locus is involved in thermoregulation mechanisms and adipogenesis, local adaptations mediated by a pathway related to the brown adipose tissue activity could have evolved in response to changing cold temperature exposures of such populations.
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http://dx.doi.org/10.4436/JASS.95011DOI Listing
December 2017

Ancient and recent admixture layers in Sicily and Southern Italy trace multiple migration routes along the Mediterranean.

Sci Rep 2017 05 16;7(1):1984. Epub 2017 May 16.

Laboratory of Molecular Anthropology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.

The Mediterranean shores stretching between Sicily, Southern Italy and the Southern Balkans witnessed a long series of migration processes and cultural exchanges. Accordingly, present-day population diversity is composed by multiple genetic layers, which make the deciphering of different ancestral and historical contributes particularly challenging. We address this issue by genotyping 511 samples from 23 populations of Sicily, Southern Italy, Greece and Albania with the Illumina GenoChip Array, also including new samples from Albanian- and Greek-speaking ethno-linguistic minorities of Southern Italy. Our results reveal a shared Mediterranean genetic continuity, extending from Sicily to Cyprus, where Southern Italian populations appear genetically closer to Greek-speaking islands than to continental Greece. Besides a predominant Neolithic background, we identify traces of Post-Neolithic Levantine- and Caucasus-related ancestries, compatible with maritime Bronze-Age migrations. We argue that these results may have important implications in the cultural history of Europe, such as in the diffusion of some Indo-European languages. Instead, recent historical expansions from North-Eastern Europe account for the observed differentiation of present-day continental Southern Balkan groups. Patterns of IBD-sharing directly reconnect Albanian-speaking Arbereshe with a recent Balkan-source origin, while Greek-speaking communities of Southern Italy cluster with their Italian-speaking neighbours suggesting a long-term history of presence in Southern Italy.
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http://dx.doi.org/10.1038/s41598-017-01802-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434004PMC
May 2017

Massive parallel sequencing of human whole mitochondrial genomes with Ion Torrent technology: an optimized workflow for Anthropological and Population Genetics studies.

Mitochondrial DNA A DNA Mapp Seq Anal 2017 11 8;28(6):843-850. Epub 2016 Nov 8.

a Laboratory of Molecular Anthropology, Department of Biological, Geological & Environmental Sciences (BiGeA) , University of Bologna , Bologna , Italy.

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.
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http://dx.doi.org/10.1080/24701394.2016.1197218DOI Listing
November 2017

A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman.

J Hum Genet 2017 Feb 13;62(2):259-264. Epub 2016 Oct 13.

Medical Genetics Unit, Department of Medical and Surgical Sciences, Polyclinic Sant'Orsola-Malpighi, University of Bologna, Bologna, Italy.

The increased risk for autosomal recessive disorders is one of the most well-known medical implications of consanguinity. In the Sultanate of Oman, a country characterized by one of the highest rates of consanguineous marriages worldwide, prevalence of genetic hearing loss (GHL) is estimated to be 6/10 000. Families of GHL patients have higher consanguinity rates than the general Omani population, indicating a major role for recessive forms. Mutations in GJB2, the most commonly mutated GHL gene, have been sporadically described. We collected 97 DNA samples of GHL probands, affected/unaffected siblings and parents from 26 Omani consanguineous families. Analyzing a first family by whole-exome sequencing, we identified a novel homozygous frameshift duplication (c.1171_1177dupGCCATCT) in MYO15A, the gene linked to the deafness locus DFNB3. This duplication was then found in a total of 8/26 (28%) families, within a 849 kb founder haplotype. Reconstruction of haplotype structure at MYO15A surrounding genomic regions indicated that the founder haplotype branched out in the past two to three centuries from a haplotype present worldwide. The MYO15A duplication emerges as the major cause of GHL in Oman. These findings have major implications for the design of GHL diagnosis and prevention policies in Oman.
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http://dx.doi.org/10.1038/jhg.2016.120DOI Listing
February 2017

Complex interplay between neutral and adaptive evolution shaped differential genomic background and disease susceptibility along the Italian peninsula.

Sci Rep 2016 09 1;6:32513. Epub 2016 Sep 1.

Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.

The Italian peninsula has long represented a natural hub for human migrations across the Mediterranean area, being involved in several prehistoric and historical population movements. Coupled with a patchy environmental landscape entailing different ecological/cultural selective pressures, this might have produced peculiar patterns of population structure and local adaptations responsible for heterogeneous genomic background of present-day Italians. To disentangle this complex scenario, genome-wide data from 780 Italian individuals were generated and set into the context of European/Mediterranean genomic diversity by comparison with genotypes from 50 populations. To maximize possibility of pinpointing functional genomic regions that have played adaptive roles during Italian natural history, our survey included also ~250,000 exomic markers and ~20,000 coding/regulatory variants with well-established clinical relevance. This enabled fine-grained dissection of Italian population structure through the identification of clusters of genetically homogeneous provinces and of genomic regions underlying their local adaptations. Description of such patterns disclosed crucial implications for understanding differential susceptibility to some inflammatory/autoimmune disorders, coronary artery disease and type 2 diabetes of diverse Italian subpopulations, suggesting the evolutionary causes that made some of them particularly exposed to the metabolic and immune challenges imposed by dietary and lifestyle shifts that involved western societies in the last centuries.
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http://dx.doi.org/10.1038/srep32513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007512PMC
September 2016

Ancient pathogen-driven adaptation triggers increased susceptibility to non-celiac wheat sensitivity in present-day European populations.

Genes Nutr 2016 23;11:15. Epub 2016 May 23.

Laboratory of Molecular Anthropology, Department of Biological, Geological and Environmental Sciences, 40126 Bologna, Italy.

Background: Non-celiac wheat sensitivity is an emerging wheat-related syndrome showing peak prevalence in Western populations. Recent studies hypothesize that new gliadin alleles introduced in the human diet by replacement of ancient wheat with modern varieties can prompt immune responses mediated by the CXCR3-chemokine axis potentially underlying such pathogenic inflammation. This cultural shift may also explain disease epidemiology, having turned European-specific adaptive alleles previously targeted by natural selection into disadvantageous ones.

Methods: To explore this evolutionary scenario, we performed ultra-deep sequencing of genes pivotal in the CXCR3-inflammatory pathway on individuals diagnosed for non-celiac wheat sensitivity and we applied anthropological evolutionary genetics methods to sequence data from worldwide populations to investigate the genetic legacy of natural selection on these loci.

Results: Our results indicate that balancing selection has maintained two divergent CXCL10/CXCL11 haplotypes in Europeans, one responsible for boosting inflammatory reactions and another for encoding moderate chemokine expression.

Conclusions: This led to considerably higher occurrence of the former haplotype in Western people than in Africans and East Asians, suggesting that they might be more prone to side effects related to the consumption of modern wheat varieties. Accordingly, this study contributed to shed new light on some of the mechanisms potentially involved in the disease etiology and on the evolutionary bases of its present-day epidemiological patterns. Moreover, overrepresentation of disease homozygotes for the dis-adaptive haplotype plausibly accounts for their even more enhanced CXCR3-axis expression and for their further increase in disease risk, representing a promising finding to be validated by larger follow-up studies.
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http://dx.doi.org/10.1186/s12263-016-0532-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968434PMC
August 2016

Positive selection of lactase persistence among people of Southern Arabia.

Am J Phys Anthropol 2016 12 18;161(4):676-684. Epub 2016 Aug 18.

Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, 40126, Italy.

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.
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http://dx.doi.org/10.1002/ajpa.23072DOI Listing
December 2016

Epigenetic Variability across Human Populations: A Focus on DNA Methylation Profiles of the KRTCAP3, MAD1L1 and BRSK2 Genes.

Genome Biol Evol 2016 09 19;8(9):2760-73. Epub 2016 Sep 19.

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Italy Interdepartmental Center "L. Galvani" (C.I.G.), University of Bologna, Italy Center for Applied Biomedical Research (CRBA), St. Orsola-Malpighi University Hospital, Bologna, Italy.

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.
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http://dx.doi.org/10.1093/gbe/evw186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630933PMC
September 2016

Inferring chronological age from DNA methylation patterns of human teeth.

Am J Phys Anthropol 2016 Apr 15;159(4):585-95. Epub 2015 Dec 15.

Department of Biological, Geological and Environmental Sciences, Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Bologna, 40126, Italy.

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.
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http://dx.doi.org/10.1002/ajpa.22921DOI Listing
April 2016

Fine Dissection of Human Mitochondrial DNA Haplogroup HV Lineages Reveals Paleolithic Signatures from European Glacial Refugia.

PLoS One 2015 7;10(12):e0144391. Epub 2015 Dec 7.

Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144391PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671665PMC
June 2016

Tracing Behçet's disease origins along the Silk Road: an anthropological evolutionary genetics perspective.

Clin Exp Rheumatol 2015 Nov-Dec;33(6 Suppl 94):S60-6. Epub 2015 Sep 22.

Laboratory of Molecular Anthropology; and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Italy.

Objectives: Behçet's disease is a multifactorial vasculitis that shows its highest prevalence in geographical areas historically involved in the Silk Road, suggesting that it might have originated somewhere along these ancient trade routes. This study aims to provide a first clue towards genetic evidence for this hypothesis by testing it via an anthropological evolutionary genetics approach.

Methods: Behçet's disease variation at ancestry informative mitochondrial DNA control region and haplogroup diagnostic sites was characterised in 185 disease subjects of Italian descent and set into the Eurasian mitochondrial landscape by comparison with nearly 9,000 sequences representative of diversity observable in Italy and along the main Silk Road routes.

Results: Dissection of the actual genetic ancestry of disease individuals by means of population structure, spatial autocorrelation and haplogroup analyses revealed their closer relationships with some Middle Eastern and Central Asian groups settled along the Silk Road than with healthy Italians.

Conclusions: These findings support the hypothesis that the Behçet's disease genetic risk has migrated to western Eurasia in parallel with ancestry components typical of Silk Road-related groups. This provided new insights that are useful to improve the understanding of disease origins and diffusion, as well as to inform future association studies aimed at properly accounting for the actual genetic ancestry of the examined Behçet's disease samples in order to minimise the detection of spurious associations and to improve the identification of genetic variants with actual clinical relevance.
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January 2016

Inferring the genetic history of lactase persistence along the Italian peninsula from a large genomic interval surrounding the LCT gene.

Am J Phys Anthropol 2015 Dec 15;158(4):708-18. Epub 2015 Jul 15.

Laboratory of Molecular Anthropology, Department of Biological, Geological and Environmental Sciences (BiGeA), University of Bologna, Bologna, 40126, Italy.

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.
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http://dx.doi.org/10.1002/ajpa.22814DOI Listing
December 2015