139 results on '"Sazzini, M."'
Search Results
2. Grasping the genetic determinants of human adaptations: the 'Kings of the Mountains' (Sherpa) case study
- Author
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Sazzini M. and Sazzini M.
- Subjects
Nepal ,Human adaptive evolution ,High-altitude Himalayan population ,Natural selection ,Altitude ,Humans ,Adaptation, Physiological - Abstract
Considerable biological and cultural adaptabilities represent some of the main strengths of the Homo sapiens species and probably the cornerstone on which our amazing evolutionary success is based. These characteristics have provided key prerequisites for anatomically modern humans to spread all over the world and to effectively colonize a variety of environmental and ecological contexts, which triggered diversified metabolic, immune and physiological changes in the human body (Hancock et al., 2011; Brown, 2012; Jeong & Di Rienzo, 2014). Having been forced to face multiple and severe selective pressures during their relatively recent evolutionary history, populations that have settled at high altitude can be viewed as some of the most iconic examples of human biological adaptability.
- Published
- 2020
3. Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine and Idarubicin
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Iacobucci, I, Lonetti, A, Candoni, A, Sazzini, M, Papayannidis, C, Formica, S, Ottaviani, E, Ferrari, A, Michelutti, A, Simeone, E, Astolfi, A, Abbenante, M C, Parisi, S, Cattina, F, Malagola, M, Russo, D, Damiani, D, Gherlinzoni, F, Gottardi, M, Baccarani, M, Fanin, R, and Martinelli, G
- Published
- 2013
- Full Text
- View/download PDF
4. IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis
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Soverini, S, Score, J, Iacobucci, I, Poerio, A, Lonetti, A, Gnani, A, Colarossi, S, Ferrari, A, Castagnetti, F, Rosti, G, Cervantes, F, Hochhaus, A, Delledonne, M, Ferrarini, A, Sazzini, M, Luiselli, D, Baccarani, M, Cross, N C P, and Martinelli, G
- Published
- 2011
- Full Text
- View/download PDF
5. An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) gene
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Sazzini, M, Zuntini, R, Farjadian, S, Quinti, I, Ricci, G, Romeo, G, Ferrari, S, Calafell, F, and Luiselli, D
- Published
- 2009
- Full Text
- View/download PDF
6. DNA methylation in human teeth as a molecular mechanism for age-estimation: a preliminary study focused on the cementum, dentin and pulp of teeth from modern individuals
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Giuliani C., Cilli E., Bacalini M. G., Pirazzini C., Sazzini M., Gruppioni G., Franceschi C., Garagnani P., Luiselli D., Olga Rickards, Lucia Sarti, and Giuliani C., Cilli E., Bacalini M.G., Pirazzini C., Sazzini M., Gruppioni G., Franceschi C., Garagnani P., Luiselli D.
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DNA methylation, age-estimation, teeth, ELOVL2 - Published
- 2016
7. Italian isolates today: geographic and linguistic factors shaping human biodiversity
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Destro Bisol, G, Anagnostou, P, Batini, C, Battaggia, C, Bertoncini, S, Boattini, A, Caciagli, L, Caló, M, Capelli, C, Capocasa, M, Castrí, L, Ciani, G, Coia, V, Corrias, L, Crivellaro, F, Ghiani, M, Luiselli, D, Mela, C, Melis, A, Montano, V, Paoli, G, Sanna, E, Rufo, F, Sazzini, M, and Taglioli, L
- Abstract
We briefly review the current status of anthropological and genetic studies of isolated populations and of their micro-evolutionary and biomedical applications, with particular emphasis on European populations. Thereafter, we describe the ongoing collaborative research project "Isolating the Isolates: geographic and cultural factors of human genetic variation" regarding Italian extant geographical and/or linguistic isolates, aimed at overcoming the limitations of previous studies regarding geographical coverage of isolates, number and type of genetic polymorphisms under study and suitability of the experimental design to investigate gene-culture coevolutionary processes. An interdisciplinary sampling approach will make it possible to collect several linguistic isolates and their geographic neighbours from Trentino, Veneto, Friuli, Tuscany, Sardinia and Calabria. This will be coupled with a shared genotyping strategy based on mitochondrial and Y-chromosomal polymorphisms. The results will be analyzed with a focus on the role of geographical and cultural factors in shaping human biodiversity. The aims of the project go beyond the simple reconstruction of the genetic structure and history of the examined groups. In fact, the study will also include an assessment for future bio-medical studies and the development of genetic and bio-demographic databases. Ethical and educational aspects are also foreseen by the project, by using informed consents together with disseminating activities in loco, completed by the creation of a dedicated web site for both scientific and public audiences.
- Published
- 2016
8. Exploring microbiota biodiversity through massive parallel sequencing with the ion torrent PGM platform
- Author
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De Fanti, S., Quagliariello, A., Aloisio, I., Sazzini, M., Corvaglia, L.T., Albanese, D., De Filippo, C., Di Gioia, D., and Luiselli, D.
- Subjects
Settore BIO/11 - BIOLOGIA MOLECOLARE ,Microbiome and human genome co-evolution ,Microbiota ,Massive parallel sequencing ,Human evolution - Published
- 2015
9. Fine Dissection of Human Mitochondrial DNA Haplogroup HV Lineages Reveals Paleolithic Signatures from European Glacial Refugia
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Fanti, S., Barbieri, C., Sarno, S., Sevini, F., Vianello, D., Tamm, E., Metspalu, E., van Oven, M., Hübner, A., Sazzini, M., Franceschi, C., Pettener, D., Luiselli, D., De Fanti, Sara, Barbieri, Chiara, Sarno, Stefania, Sevini, Federica, Vianello, Dario, Tamm, Erika, Metspalu, Ene, van Oven, Manni, Hübner, Alexander, Sazzini, Marco, Franceschi, Claudio, Pettener, Davide, Luiselli, Donata, and Genetic Identification
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Geography ,Molecular Sequence Data ,lcsh:R ,Genetic Variation ,lcsh:Medicine ,Mitochondrial haplogroups, Italian peninsula, Epigravettian, Phylogeography, BEAST ,DNA, Mitochondrial ,White People ,Mitochondria ,Europe ,Phylogeography ,Genetics, Population ,Haplotypes ,Ethnicity ,Humans ,Cell Lineage ,lcsh:Q ,lcsh:Science ,Research Article - Abstract
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.
- Published
- 2015
10. Italian isolates today: geographic and linguistic factors shaping human biodiversity
- Author
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Bisol, G. D., Anagnostou, P., Batini, C., Battaggia, C., Bertoncini, S., Boattini, A., Caciagli, L., Calò, C. M., Capelli, C., Capocasa, M., Castrì, L., Ciani, G., Cola, V., Corrias, L., Federica Crivellaro, Ghiani, M. E., Luiselli, D., Mela, C., Melis, A., Montano, V., Paoli, G., Sanna, E., Rufo, F., Sazzini, M., Taglloli, L., Tofanelli, S., Useli, A., Vona, G., Pettener, D., DESTRO BISOL G., ANAGNOSTOU P., BATINI C., BATTAGGIA C., BERTONCINI S., BOATTINI A., CACIAGLI L., CALO’ C.M., CAPELLI C., CAPOCASA M., CASTRI’ L., CIANI G., COIA V., CORRIAS L., CRIVELLARO F., GHIANI M.E., LUISELLI D., MELA C., MELIS A., MONTANO V., PAOLI G., SANNA E., RUFO F., SAZZINI M., TAGLIOLI L., TOFANELLI S., USELI A., VONA G., and PETTENER D.
- Subjects
language ,isolates ,italy ,geography ,population genetics - Abstract
We briefly review the current status of anthropological and genetic studies of isolated populations and of their micro-evolutionary and biomedical applications, with particular emphasis on European populations. Thereafter, we describe the ongoing collaborative research project "Isolating the Isolates: geographic and cultural factors of human genetic variation" regarding Italian extant geographical and/or linguistic isolates, aimed at overcoming the limitations of previous studies regarding geographical coverage of isolates, number and type of genetic polymorphisms under study and suitability of the experimental design to investigate gene-culture coevolutionary processes. An interdisciplinary sampling approach will make it possible to collect several linguistic isolates and their geographic neighbours from Trentino, Veneto, Friuli, Tuscany, Sardinia and Calabria. This will be coupled with a shared genotyping strategy based on mitochondrial and Y-chromosomal polymorphisms. The results will be analyzed with a focus on the role of geographical and cultural factors in shaping human biodiversity. The aims of the project go beyond the simple reconstruction of the genetic structure and history of the examined groups. In fact, the study will also include an assessment for future bio-medical studies and the development of genetic and bio-demographic databases. Ethical and educational aspects are also foreseen by the project, by using informed consents together with disseminating activities in loco, completed by the creation of a dedicated web site for both scientific and public audiences.
- Published
- 2009
11. L’efficienza dell’imputing confrontando individui genotipizzati con 2 piattaforme diverse
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Mijatovic, Vladan, Malerba, Giovanni, Iacobucci, I., Xumerle, Luciano, Sazzini, M., Mori, Antonio, Martinelli, Giovanni, and Pignatti, Pierfranco
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inputing ,malattie complesse ,genotipizzazione ,bioinformatica - Published
- 2011
12. TNFRSF13B gene variability in Italian CVID and IgAD patients: a population study
- Author
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Ferrari, S, Zuntini, R, Sazzini, M, Ricci, G, Quinti, Isabella, Romeo, G, and Luiselli, D.
- Published
- 2008
13. Searching for signatures of cold adaptations in modern and archaic humans: hints from the brown adipose tissue genes
- Author
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Sazzini, M, primary, Schiavo, G, additional, De Fanti, S, additional, Martelli, P L, additional, Casadio, R, additional, and Luiselli, D, additional
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- 2014
- Full Text
- View/download PDF
14. Between europe and the mediterranean: high resolution Y-Chromosome structure of Italy - preliminary results
- Author
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Sarno, S., primary, Boattini, A., additional, Yang Yao, D., additional, De Fanti, S., additional, Sazzini, M., additional, Ciani, G., additional, Useli, A., additional, Martinez-Cruz, B., additional, Bertranpetit, J., additional, Comas, D., additional, Luiselli, D., additional, and Pettener, D., additional
- Published
- 2012
- Full Text
- View/download PDF
15. An exploratory picture of the iranian mtDNA landscape
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Farjadian, S., primary, Sazzini, M., additional, Tofanelli, S., additional, Castrì, L., additional, Taglioli, L., additional, Pettener, D., additional, Ghaderi, A., additional, Romeo, G., additional, and Luiselli, D., additional
- Published
- 2012
- Full Text
- View/download PDF
16. Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine and Idarubicin
- Author
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Iacobucci, I, primary, Lonetti, A, additional, Candoni, A, additional, Sazzini, M, additional, Papayannidis, C, additional, Formica, S, additional, Ottaviani, E, additional, Ferrari, A, additional, Michelutti, A, additional, Simeone, E, additional, Astolfi, A, additional, Abbenante, M C, additional, Parisi, S, additional, Cattina, F, additional, Malagola, M, additional, Russo, D, additional, Damiani, D, additional, Gherlinzoni, F, additional, Gottardi, M, additional, Baccarani, M, additional, Fanin, R, additional, and Martinelli, G, additional
- Published
- 2012
- Full Text
- View/download PDF
17. Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia
- Author
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Iacobucci, I, primary, Ferrarini, A, additional, Sazzini, M, additional, Giacomelli, E, additional, Lonetti, A, additional, Xumerle, L, additional, Ferrari, A, additional, Papayannidis, C, additional, Malerba, G, additional, Luiselli, D, additional, Boattini, A, additional, Garagnani, P, additional, Vitale, A, additional, Soverini, S, additional, Pane, F, additional, Baccarani, M, additional, Delledonne, M, additional, and Martinelli, G, additional
- Published
- 2012
- Full Text
- View/download PDF
18. A Clinical Phenotype Mimicking Essential Hypertension in a Newly Discovered Family With Liddle's Syndrome
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Rossi, E., primary, Farnetti, E., additional, Nicoli, D., additional, Sazzini, M., additional, Perazzoli, F., additional, Regolisti, G., additional, Grasselli, C., additional, Santi, R., additional, Negro, A., additional, Mazzeo, V., additional, Mantero, F., additional, Luiselli, D., additional, and Casali, B., additional
- Published
- 2011
- Full Text
- View/download PDF
19. IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis
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Soverini, S, primary, Score, J, additional, Iacobucci, I, additional, Poerio, A, additional, Lonetti, A, additional, Gnani, A, additional, Colarossi, S, additional, Ferrari, A, additional, Castagnetti, F, additional, Rosti, G, additional, Cervantes, F, additional, Hochhaus, A, additional, Delledonne, M, additional, Ferrarini, A, additional, Sazzini, M, additional, Luiselli, D, additional, Baccarani, M, additional, Cross, N C P, additional, and Martinelli, G, additional
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- 2010
- Full Text
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20. Use of deep whole transcriptome sequencing in Philadelphia-positive acute lymphoblastic leukemia (ALL) to identify novel mutated genes and aberrant gene expression and alternative splicing profiles associated with disease progression.
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Iacobucci, I., primary, Ferrarini, A., additional, Sazzini, M., additional, Lonetti, A., additional, Giacomelli, E., additional, Xumerle, L., additional, Ferrari, A., additional, Papayannidis, C., additional, Delledonne, M., additional, and Martinelli, G., additional
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- 2010
- Full Text
- View/download PDF
21. MAPPING WHOLE-EXOME SEQUENCING DATA OF ACUTE MYELOID LEUKEMIA PATIENTS INTO KEGG PATHWAYS
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Padella, A., Simonetti, G., Iacobucci, I., Dovalle, I., Zago, E., Griggio, F., Garonzi, M., Manfrini, M., Guadagnuolo, V., Bernardi, S., CRISTINA PAPAYANNIDIS, Abbenante, M. C., Marconi, G., Melloni, G., Riva, L., Bruno, S., Fontana, M. C., Zuffa, E., Franchini, E., Baldazzi, C., Cavo, M., Testoni, N., Ottaviani, E., Pellicci, P. G., Sazzini, M., Ferrarini, A., Delledonne, M., Remondini, D., and Martinelli, G.
22. MAPPING WHOLE-EXOME SEQUENCING DATA INTO KEGG PATHWAYS GIVES INSIGHTS FOR RISK STRATIFICATION OF ACUTE MYELOID LEUKEMIA PATIENTS
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Padella, A., Simonetti, G., Dovalle, I., Ferrari, A., Iacobucci, I., Zago, E., Griggio, F., Garonzi, M., Manfrini, M., Guadagnuolo, V., CRISTINA PAPAYANNIDIS, Abbenante, M. C., Marconi, G., Melloni, G., Riva, L., Bruno, S., Testoni, N., Ottaviani, E., Pelicci, P. G., Sazzini, M., Ferrarini, A., Delledonne, M., Remondini, D., and Martinelli, G.
23. WHOLE EXOME SEQUENCING IDENTIFIES MUTATIONS OF ALDH2, IMPDH2, RETSAT, HSPG2, CHPF AND OTHER METABOLIC GENES AS A NOVEL FUNCTIONAL CATEGORY OF GENOMIC ALTERATIONS IN ACUTE MYELOID LEUKEMIA
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Simonetti, G., Padella, A., Iacobucci, I., Dovalle, I., Fontanarosa, G., Zago, E., Griggio, F., Garonzi, M., Bernardi, S., CRISTINA PAPAYANNIDIS, Abbenante, M. C., Marconi, G., Melloni, G., Riva, L., Guadagnuolo, V., Fontana, M. C., Bruno, S., Ferrari, A., Zuffa, E., Franchini, E., Astolfi, A., Baldazzi, C., Dan, E., Sinigaglia, B., Cavo, M., Testoni, N., Ottaviani, E., Pelicci, P. G., Sazzini, M., Ferrarini, A., Delledonne, M., Remondini, D., and Martinelli, G.
24. EUROPEAN NETWORK NGS-PTL PRELIMINARY DATA: WHOLE EXOME SEQUENCING IDENTIFIES MUTATIONS OF ALDH2, RETSAT, HSPG2, CHPF, AND OTHER METABOLIC GENES AS A NOVEL FUNCTIONAL CATEGORY IN ACUTE MYELOID LEUKEMIA
- Author
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Simonetti, G., Padella, A., Iacobucci, I., Dovalle, I., Fontanarosa, G., Zago, E., Griggio, F., Garonzi, M., Bernardi, S., CRISTINA PAPAYANNIDIS, Abbenante, M. C., Marconi, G., Melloni, G., Riva, L., Guadagnuolo, V., Fontana, M., Bruno, S., Zuffa, E., Franchini, E., Astolfi, A., Baldazzi, C., Dan, E., Sinigaglia, B., Cavo, M., Testoni, N., Ottaviani, E., Pelicci, P. G., Sazzini, M., Ferrarini, A., Delledonne, M., Remondini, D., and Martinelli, G.
25. An Exploratory Picture of the Iranian nntDNA Landscape.
- Author
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Farjadian, S., Sazzini, M., Tofanelli, S., Castri, L., Taglioli, L., Pettener, D., Ghaderi, A., Romeo, G., and Luiselli, D.
- Subjects
- *
MITOCHONDRIAL DNA , *IRANIANS , *POPULATION genetics , *ETHNIC groups , *INDO-Europeans - Abstract
The article presents the study which examined the mitochondrial DNA (mtDNA) of the Iranian population as of January 2012. Among the possible ancestors of majority of Iranians are the Aryans and Indo-European nomadic tribes. In the study, the various Iranian ethnic groups that were studied include Balochis, Mazandaranis, and Qashqaees.
- Published
- 2012
- Full Text
- View/download PDF
26. Between Europe and the Mediterranean: High Resolution V-Chromosonne Structure of Italy - Prelinninary Results.
- Author
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Sarno, S., Boattini, A., Yao, D. Yang, De Fanti, S., Sazzini, M., Ciani, G., Useli, A., Martinez-Cruz, B., Bertranpetit, J., Comas, D., Luiselli, D., and Pettener, D.
- Subjects
ITALIANS ,POPULATION genetics ,BIOMARKERS ,PRINCIPAL components analysis ,Y chromosome - Abstract
The article presents the study which examined the genetic history of the Italian population as of January 2012. In the study, the resolution power of Y-chromosome uniparental molecular markers is analyzed. Among the methods used in the study are the preliminary surname-based analysis, the TaMan Assays, and the Principal Component Analysis.
- Published
- 2012
- Full Text
- View/download PDF
27. Altitude-Induced Sleep Apnea Is Highly Dependent on Ethnic Background (Sherpa Vs. Tamang)
- Author
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Grégory Heiniger, Simon Walbaum, Claudio Sartori, Alban Lovis, Marco Sazzini, Andrew Wellman, Raphael Heinzer, Heiniger G., Walbaum S., Sartori C., Lovis A., Sazzini M., Wellman A., and Heinzer R.
- Subjects
Adult ,Male ,Physiology ,Public Health, Environmental and Occupational Health ,loop gain ,General Medicine ,Altitude Sickness ,Carbon Dioxide ,Sleep Apnea, Central ,genetic ancestry ,periodic breathing ,central sleep apnea ,Oxygen ,Young Adult ,Sleep Apnea Syndromes ,Ethnicity ,Humans ,altitude - Abstract
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/m(2) vs. 25.21 [20.6-27.6] kg/m(2)). 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.
- Published
- 2022
28. Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans
- Author
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Sebastiano Collino, Alberto Ferrarini, Armand Valsesia, Daniela Monti, Beatrice Arosio, Davide Pettener, Paolo Garagnani, Frederic Raymond, Jérôme Carayol, Julien Marquis, Stefania Sarno, Patrizia D'Aquila, Claudio Franceschi, Donata Luiselli, Sara De Fanti, Daniela Mari, Paolo Abondio, Matteo Ragno, Guido Alberto Gnecchi-Ruscone, Massimo Delledonne, Cristina Giuliani, Patrick Descombes, Marco Sazzini, Luciano Xumerle, Giuseppe Passarino, Chiara Pirazzini, Gastone Castellani, Alessio Boattini, Elena Marasco, Claudia Ojeda-Granados, Sazzini M., Abondio P., Sarno S., Gnecchi-Ruscone G.A., Ragno M., Giuliani C., De Fanti S., Ojeda-Granados C., Boattini A., Marquis J., Valsesia A., Carayol J., Raymond F., Pirazzini C., Marasco E., Ferrarini A., Xumerle L., Collino S., Mari D., Arosio B., Monti D., Passarino G., D'Aquila P., Pettener D., Luiselli D., Castellani G., Delledonne M., Descombes P., Franceschi C., and Garagnani P.
- Subjects
Physiology ,Plant Science ,Human genetic variation ,Demographic inference ,Evolutionary medicine ,Italian population ,Polygenic adaptation ,Whole-genome sequences ,Gene flow ,0302 clinical medicine ,Structural Biology ,lcsh:QH301-705.5 ,0303 health sciences ,education.field_of_study ,Genome ,Cline (biology) ,Archaeology ,Italy ,Gene pool ,General Agricultural and Biological Sciences ,Research Article ,Human ,Biotechnology ,Evolution ,European Continental Ancestry Group ,Population ,Biology ,White People ,General Biochemistry, Genetics and Molecular Biology ,Ancient ,Evolution, Molecular ,03 medical and health sciences ,Genetic variation ,Humans ,DNA, Ancient ,education ,Evolutionary dynamics ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Genome, Human ,Genetic Variation ,Molecular ,DNA ,Cell Biology ,lcsh:Biology (General) ,Evolutionary biology ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
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.
- Published
- 2020
29. Application of the whole-transcriptome shotgun sequencing approach to the study of Philadelphia-positive acute lymphoblastic leukemia
- Author
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Cristina Papayannidis, Simona Soverini, Marco Sazzini, Paolo Garagnani, Antonella Vitale, Fabrizio Pane, Donata Luiselli, E. Giacomelli, Giovanni Martinelli, Alberto Ferrarini, Luciano Xumerle, Anna Maria Ferrari, Alessio Boattini, Ilaria Iacobucci, Giovanni Malerba, Michele Baccarani, Annalisa Lonetti, Massimo Delledonne, Iacobucci, I, Ferrarini, A, Sazzini, M, Giacomelli, E, Lonetti, A, Xumerle, L, Ferrari, A, Papayannidis, C, Malerba, G, Luiselli, D, Boattini, A, Garagnani, P, Vitale, A, Soverini, S, Pane, Fabrizio, Baccarani, M, Delledonne, M, Martinelli, G., Iacobucci I., Ferrarini A., Sazzini M., Giacomelli E., Lonetti A., Xumerle L., Ferrari A., Papayannidis C., Malerba G., Luiselli D., Boattini A., Garagnani P., Vitale A., Soverini S., Pane F., Baccarani M., Delledonne M., and Martinelli G.
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Genetics ,ABL ,Shotgun sequencing ,Alternative splicing ,RNA-Seq ,Hematology ,acute lymphoblastic leukemia ,sequencing ,Biology ,BCR-ABL1 ,RNA-seq ,Philadelphia-positive ,Transcriptome ,Oncology ,Fusion transcript ,hemic and lymphatic diseases ,Original Article ,ALL ,Gene ,Reference genome - Abstract
Although the pathogenesis of BCR-ABL1-positive acute lymphoblastic leukemia (ALL) is mainly related to the expression of the BCR-ABL1 fusion transcript, additional cooperating genetic lesions are supposed to be involved in its development and progression. Therefore, in an attempt to investigate the complex landscape of mutations, changes in expression profiles and alternative splicing (AS) events that can be observed in such disease, the leukemia transcriptome of a BCR-ABL1-positive ALL patient at diagnosis and at relapse was sequenced using a whole-transcriptome shotgun sequencing (RNA-Seq) approach. A total of 13.9 and 15.8 million sequence reads was generated from de novo and relapsed samples, respectively, and aligned to the human genome reference sequence. This led to the identification of five validated missense mutations in genes involved in metabolic processes (DPEP1, TMEM46), transport (MVP), cell cycle regulation (ABL1) and catalytic activity (CTSZ), two of which resulted in acquired relapse variants. In all, 6390 and 4671 putative AS events were also detected, as well as expression levels for 18 315 and 18 795 genes, 28% of which were differentially expressed in the two disease phases. These data demonstrate that RNA-Seq is a suitable approach for identifying a wide spectrum of genetic alterations potentially involved in ALL.
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- 2012
30. Investigating Mitonuclear Genetic Interactions Through Machine Learning: A Case Study on Cold Adaptation Genes in Human Populations From Different European Climate Regions
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Alena Kalyakulina, Vincenzo Iannuzzi, Marco Sazzini, Paolo Garagnani, Sarika Jalan, Claudio Franceschi, Mikhail Ivanchenko, Cristina Giuliani, Kalyakulina A., Iannuzzi V., Sazzini M., Garagnani P., Jalan S., Franceschi C., Ivanchenko M., and Giuliani C.
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0301 basic medicine ,Mitochondrial DNA ,Nuclear gene ,Physiology ,Population ,mitonuclear interactions ,Biology ,Machine learning ,computer.software_genre ,lcsh:Physiology ,03 medical and health sciences ,human evolution ,0302 clinical medicine ,human ecology ,Physiology (medical) ,Evolutionary dynamics ,education ,Original Research ,Local adaptation ,education.field_of_study ,lcsh:QP1-981 ,human populations ,business.industry ,human population ,machine learning ,030104 developmental biology ,Human evolution ,cold adaptation ,Genetic structure ,Biological dispersal ,Artificial intelligence ,business ,computer ,030217 neurology & neurosurgery - Abstract
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” FTO 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.
- Published
- 2020
31. Genomic adaptations to cereal-based diets contribute to mitigate metabolic risk in some human populations of East Asian ancestry
- Author
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Giovanni Romeo, Guido Alberto Gnecchi-Ruscone, Davide Gentilini, Thanh Tin Nguyen, Stefania Sarno, Marco Sazzini, Shaobo Yu, Sara De Fanti, Donata Luiselli, Cecilia Prata, Eugenio Bortolini, Anna Maria Di Blasio, Davide Pettener, Arianna Landini, Claudia Ojeda-Granados, Paolo Abondio, Hanjun Jin, Landini A., Yu S., Gnecchi-Ruscone G.A., Abondio P., Ojeda-Granados C., Sarno S., De Fanti S., Gentilini D., Di Blasio A.M., Jin H., Nguyen T.T., Romeo G., Prata C., Bortolini E., Luiselli D., Pettener D., and Sazzini M.
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0106 biological sciences ,0301 basic medicine ,lcsh:Evolution ,Zoology ,Type 2 diabetes ,Biology ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,Insulin resistance ,lcsh:QH359-425 ,dietary selective pressure ,Genetics ,medicine ,Glucose homeostasis ,East Asia ,Domestication ,Ecology, Evolution, Behavior and Systematics ,2. Zero hunger ,dietary selective pressures ,genomic adaptation ,food and beverages ,Staple food ,Original Articles ,medicine.disease ,Obesity ,030104 developmental biology ,Glycemic index ,metabolic risk ,evolutionary medicine ,human Asian populations ,Original Article ,human Asian population ,General Agricultural and Biological Sciences - Abstract
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 glycaemic 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. 1 Introduction 2 Methods 2.1 Samples collection and genotyping 2.2 Data curation and assembly of a Pan-Asian dataset 2.3 Population structure analyses 2.4 Selection scans on the identified population clusters 2.5 Shortlisting of the most informative candidate adaptive genes 2.6 Gene network analyses aimed at testing for polygenic adaptation 3 Results 3.1 Exploring population structure in the assembled Pan-Asian dataset 3.2 Identification of genetically homogeneous population clusters 3.3 Detection of genomic regions enriched for selective sweeps in each population cluster 3.4 Fine mapping of the most informative candidate adaptive genes 3.5 Investigation of polygenic adaptive events in the Han-Tujia and Japanese clusters 4 Discussion 4.1 Population clusters within the South Asianand East Asian genomic landscapes 4.2 Distinctive patterns of adaptive evolution in candidate and control population clusters
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- 2019
32. The Genetic Variability of APOE in Different Human Populations and Its Implications for Longevity
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Cristina Giuliani, Donata Luiselli, Paolo Garagnani, Paolo Abondio, Daniela Monti, Alessio Boattini, Marco Sazzini, Claudio Franceschi, Abondio P., Sazzini M., Garagnani P., Boattini A., Monti D., Franceschi C., Luiselli D., and Giuliani C.
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0301 basic medicine ,Apolipoprotein E ,Multifactorial Inheritance ,lcsh:QH426-470 ,media_common.quotation_subject ,Population genetics ,Genomics ,Genome-wide association study ,Review ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Apolipoproteins E ,longevity ,Genetics ,genomics ,Humans ,Genetic variability ,Allele ,Evolutionary dynamics ,Genetics (clinical) ,media_common ,apolipoprotein E ,Longevity ,Genetic Variation ,populations ,lcsh:Genetics ,030104 developmental biology ,Genetics, Population ,Haplotypes ,Evolutionary biology ,Genomic ,030217 neurology & neurosurgery ,APOE ,Populations - Abstract
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.
- Published
- 2019
33. Testing novel candidate loci for adaptive introgression due to gene flow between Denisovans and the ancestors of modern East Asian populations
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Castellani N., Shahpari A., Abondio P., Gnecchi-Ruscone G. A., Samo S., Sherpa P. T., Marinelli G., Cocco P., Natali L., Di Marcello, M. Peluzzi, D. Pettener, D. Luiselli, D. Sazzini, and Castellani, N., Shahpari, A., Abondio, P., Gnecchi-Ruscone, G.A., Samo, S., Sherpa, P.T., Marinelli, G., Cocco, P., Natali, L., Di Marcello, M., Peluzzi, D., Pettener, D., Luiselli, D., Sazzini, M.
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Archaic adaptive introgression, Denisovans, East Asian populations - Published
- 2019
34. Gut microbiota composition in Himalayan and Andean populations and its relationship with diet, lifestyle and adaptation to the high-altitude environment
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Andrea, Quagliariello, Monica, Di Paola, Sara, De Fanti, Guido Alberto, Gnecchi-Ruscone, Lucia, Martinez-Priego, David, Pérez-Villaroya, Mingma G, Sherpa, Phurba T, Sherpa, Giorgio, Marinelli, Luca, Natali, Marco, Di Marcello, Davide, Peluzzi, Patrizia, Di Cosimo, Giuseppe, D'Auria, Davide, Pettener, Marco, Sazzini, Donata, Luiselli, Carlotta, De Filippo, Quagliariello A., Di Paola M., De Fanti S., Gnecchi-Ruscone G.A., Martinez-Priego L., Perez-Villaroya D., Sherpa M.G., Sherpa P.T., Marinelli G., Natali L., Di Marcello M., Peluzzi D., Di Cosimo P., D'auria G., Pettener D., Sazzini M., Luiselli D., and De Filippo C.
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Adult ,Male ,Bolivia ,Host-microbe coevolution ,Dietary habits ,Physiological ,Altitude ,Gut microbiota ,Dietary habit ,Adaptation, Physiological ,Biological Evolution ,Diet ,Gastrointestinal Microbiome ,Mountaineering ,Young Adult ,Nepal ,Human adaptive evolution ,Humans ,Female ,High-altitude adaptation ,Adaptation ,Life Style - Abstract
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.
- Published
- 2019
35. Ancient and recent admixture layers in Sicily and Southern Italy trace multiple migration routes along the Mediterranean
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Alessio Boattini, Luca Pagani, Stefania Sarno, Luca Sineo, Guido Alberto Gnecchi Ruscone, Donata Luiselli, Marco Sazzini, Rosalba Petrilli, Ilia Mikerezi, Miguel G. Vilar, Chiara Barbieri, Eugenio Bortolini, Davide Pettener, Graziella Ciani, Elisabetta Cilli, Etienne Guichard, Spencer Wells, Sara De Fanti, Andrea Quagliariello, Sarno, S, Boattini, A, Pagani, L, Sazzini, M, De Fanti, S, Quagliariello, A, Gnecchi Ruscone, GA, Guichard, E, Ciani, G, Bortolini, E, Barbieri, C, Cilli, E, Petrilli, R, Mikerezi, I, Sineo, L, Vilar, M, Wells, S, Luiselli, D, Pettener, D, Sarno, Stefania, Boattini, Alessio, Pagani, Luca, Sazzini, Marco, De Fanti, Sara, Quagliariello, Andrea, Gnecchi Ruscone, Guido Alberto, Guichard, Etienne, Ciani, Graziella, Bortolini, Eugenio, Barbieri, Chiara, Cilli, Elisabetta, Petrilli, Rosalba, Mikerezi, Ilia, Sineo, Luca, Vilar, Miguel, Wells, Spencer, Luiselli, Donata, and Pettener, Davide
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0301 basic medicine ,Mediterranean climate ,Multidisciplinary ,Cultural history ,Southern Italy, Sicily, genomic ancestry, admxiture, Mediterranean populations ,Science ,Biological anthropology ,Settore BIO/08 - Antropologia ,Archaeology ,Article ,03 medical and health sciences ,030104 developmental biology ,Geography ,DNA, Sicily, Southern Italy, Migration routes, Genotyping ,Medicine ,Population diversity ,Genetic variation - Abstract
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., This study was supported by the Genographic Project 2.0 (Geno 2.0) Scientific Research Grant 4–13 and by the European Research Council ERC-2011-AdG 295733 grant (Langelin).
- Published
- 2017
36. A Clinical Phenotype Mimicking Essential Hypertension in a Newly Discovered Family With Liddle's Syndrome
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Giuseppe Regolisti, Donata Luiselli, Enrico Farnetti, Rosaria Santi, Vincenzo Mazzeo, Marco Sazzini, Aurelio Negro, Davide Nicoli, Franco Perazzoli, Ermanno Rossi, Chiara Grasselli, Bruno Casali, Franco Mantero, Rossi E., Farnetti E., Nicoli D., Sazzini M., Perazzoli F., Regolisti G., Grasselli C., Santi R., Negro A., Mazzeo V., Mantero F., Luiselli D., and Casali B.
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Adult ,Male ,Proband ,medicine.medical_specialty ,Adolescent ,LIDDLE'S SYNDROME ,Hypokalemia ,Essential hypertension ,Left ventricular hypertrophy ,Amiloride ,Liddle Syndrome ,MTDNA ,Internal medicine ,Renin ,Internal Medicine ,Humans ,Medicine ,Liddle's syndrome ,Epithelial Sodium Channels ,Y CHROMOSOME ,Aldosterone ,Aged ,Genetics ,business.industry ,ENAC ,Middle Aged ,medicine.disease ,Pedigree ,Endocrinology ,Hypertension ,Mutation (genetic algorithm) ,Female ,medicine.symptom ,business ,Polymorphism, Restriction Fragment Length ,Founder effect - Abstract
BACKGROUND: Liddle's syndrome (LS) is a monogenic form of hypertension simulating a mineralocorticoid excess, and is currently suspected in young hypokalemic hypertensives. The aims of the study were: (i) to evaluate the clinical phenotype of LS in a newly identified Italian family of Sicilian origin carrying a gain-of-function mutation of the β subunit of the epithelial sodium channel (ENaC) (P617L) previously reported by our group in an apparently unrelated Sicilian patient presenting the typical phenotype of LS including hypokalemia; (ii) to determine whether an unknown biological relationship exists between the newly identified family and the family of the proband previously reported. METHODS: Genetic analysis was performed in the present family, in the individual in which the βP617L mutation was first observed, and in his relatives. RESULTS: βP617L mutation was identified in the proband and in three maternal relatives. None of them showed hypokalemia. Mild to severe early onset hypertension and left ventricular hypertrophy were present in all of them. Analysis of mitochondrial DNA (mtDNA) and Y chromosome profiles in the present family and in the proband's family previously reported showed the absence of a relationship between them. The availability of only one carrier of the mutation in one of the two families meant that a genetic analysis able to assess a founder effect was not feasible. CONCLUSIONS: LS should be considered in all cases of early onset hypertension, independently of the plasma potassium concentration. The incidence of LS may be greater than is currently thought, because hypokalemia is not invariably present.
- Published
- 2011
37. A polymorphism in the chromosome 9p21 ANRIL locus is associated to Philadelphia positive acute lymphoblastic leukemia
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Marco Sazzini, Alessio Boattini, Annalisa Lonetti, Paolo Garagnani, Anna Maria Ferrari, Emanuela Ottaviani, Michele Baccarani, Simona Soverini, Cristina Papayannidis, Ilaria Iacobucci, Vilma Mantovani, Giovanni Martinelli, Elena Marasco, Domenico Girelli, Donata Luiselli, Marco Vignetti, IACOBUCCI I., SAZZINI M., GARAGNANI P., FERRARI A., BOATTINI A., LONETTI A., PAPAYANNIDIS C., MANTOVANI V., MARASCO E., OTTAVIANI E., SOVERINI S., GIRELLI D., LUISELLI D., VIGNETTI M., BACCARANI M., and MARTINELLI G.
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Adult ,Male ,Cancer Research ,RNA, Untranslated ,Adolescent ,Single-nucleotide polymorphism ,Locus (genetics) ,CDKN2A/B and CDKN2BAS genes ,Biology ,Polymorphism, Single Nucleotide ,Cohort Studies ,Young Adult ,CDKN2A/B and CDKN2BAS genes, Single nucleotide polymorphisms, Ph+ ALL susceptibility ,cdkn2a/b and cdkn2bas genes ,ph + all susceptibility ,single nucleotide polymorphisms ,CDKN2A ,hemic and lymphatic diseases ,medicine ,Humans ,Ph+ ALL susceptibility ,Gene ,Genotyping ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Cyclin-Dependent Kinase Inhibitor p15 ,Genetics ,CDKN2BAS ,Myeloid leukemia ,Single nucleotide polymorphisms ,DNA, Neoplasm ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Molecular biology ,Leukemia, Myeloid, Acute ,Leukemia ,Oncology ,Case-Control Studies ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Female ,Chromosomes, Human, Pair 9 ,Follow-Up Studies - 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.
- Published
- 2011
38. Discordant Patterns of mtDNA and Ethno-Linguistic Variation in 14 Iranian Ethnic Groups
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Giovanni Romeo, Donata Luiselli, Loredana Castrì, Davide Pettener, Shirin Farjadian, Luca Taglioli, Marco Sazzini, Sergio Tofanelli, Abbas Ghaderi, Farjadian S., Sazzini M., Tofanelli S., Castrì L., Taglioli L., Pettener D., Ghaderi A., Romeo G., and Luiselli D.
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Gene Flow ,Mitochondrial DNA ,Ethnic group ,LANGUAGE ,Biology ,DNA, Mitochondrial ,Prehistory ,MTDNA ,Human population genetics ,Ethnicity ,Genetics ,Humans ,Phylogeny ,Genetics (clinical) ,Retrospective Studies ,Genome, Human ,Computational Biology ,Genetic Variation ,Sequence Analysis, DNA ,IRAN ,Phylogeography ,Genetics, Population ,Variation (linguistics) ,Haplotypes ,Human genome ,Algorithms - Abstract
Background/Aims: Present-day Iran has long represented a natural hub for the expansion of human genes and cultures. That being so, the overlapping of prehistoric and more recent demographic events interacting at different time scales with geographical and cultural barriers has yielded a tangled patchwork of anthropological types within this narrow area. This study aims to comprehensively evaluate this ethnic mosaic by depicting a fine-grained picture of the Iranian mitochondrial landscape. Methods: mtDNA variability at both HVS-I and coding regions was surveyed in 718 unrelated individuals belonging to 14 Iranian ethnic groups characterized by different languages, religions and patterns of subsistence. Results: A discordant pattern of high ethno-linguistic and low mtDNA heterogeneity was observed for the whole examined Iranian sample. Geographical factors and cultural/linguistic differences actually represented barriers to matrilineal gene flow only for the Baloch, Lur from Yasouj, Zoroastrian and Jewish groups, for which unusual reduced levels of mtDNA variability and high inter-population distances were found. Conclusion: Deep rooting genealogies and endogamy in a few of the examined ethnic groups might have preserved ancestral lineages that can be representative of Proto-Indo-Iranian or prehistoric mitochondrial profiles which survived relatively recent external contributions to the Iranian gene pool.
- Published
- 2011
39. IDH2 somatic mutations in chronic myeloid leukemia patients in blast crisis
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Andreas Hochhaus, Sabrina Colarossi, Massimo Delledonne, Nicholas C.P. Cross, Angela Poerio, Fausto Castagnetti, Annalisa Lonetti, Alberto Ferrarini, Ilaria Iacobucci, Simona Soverini, Michele Baccarani, Marco Sazzini, Giovanni Martinelli, Alberto Ferrari, Giovanni Rosti, Alessandra Gnani, Donata Luiselli, Francisco Cervantes, Joannah Score, Soverini S., Score J., Iacobucci I., Poerio A., Lonetti A., Gnani A., Colarossi S., Ferrari A., Castagnetti F., Rosti G., Cervantes F., Hochhaus A., Delledonne M., Ferrarini A., Sazzini M., Luiselli D., Baccarani M., Cross NC., and Martinelli G.
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CHRONIC MYELOID LEUKEMIA ,Cancer Research ,IDH1 ,Myelodysplastic syndromes ,Myeloid leukemia ,Hematology ,Biology ,medicine.disease ,IDH2 ,deep sequencing ,Myelogenous ,Leukemia ,Isocitrate dehydrogenase ,Oncology ,hemic and lymphatic diseases ,Immunology ,medicine ,Cancer research ,chronic myeloid leukemia ,mutation ,Chronic myelogenous leukemia - Abstract
We read with interest a series of manuscripts,1, 2, 3, 4, 5, 6 reporting somatic mutations of the isocitrate dehydrogenase 1 and 2 enzyme isoforms (IDH1, IDH2) in patients with de novo acute myeloid leukemia (AML), in patients with chronic and blast phase Philadelphia chromosome-negative (Ph–) myeloproliferative neoplasms (MPNs) and in patients with early and accelerated phase myelodysplastic syndromes (MDSs).We have recently screened, by massively parallel sequencing, the transcriptome of a Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) patient
- Published
- 2010
40. Inferring the genetic history of lactase persistence along the Italian peninsula from a large genomic interval surrounding the LCT gene
- Author
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Sara, De Fanti, Marco, Sazzini, Cristina, Giuliani, Federica, Frazzoni, Stefania, Sarno, Alessio, Boattini, Elena, Marasco, Vilma, Mantovani, Claudio, Franceschi, Pedro, Moral, Paolo, Garagnani, Donata, Luiselli, De Fanti, S, Sazzini, M, Giuliani, C, Frazzoni, F, Sarno, S, Boattini, A, Marasco, E, Mantovani, V, Franceschi, C, Moral, P, Garagnani, P, and Luiselli, D.
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Mediterranean human population ,Human Migration ,natural selection ,anthropological genetic ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,White People ,lactose tolerance ,Lactose Intolerance ,Gene Frequency ,Haplotypes ,Italy ,Humans ,Selection, Genetic ,Lactase - Abstract
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
- Published
- 2015
41. The epigenetic side of human adaptation: hypotheses, evidences and theories
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Maria Giulia Bacalini, Claudio Franceschi, Cristina Giuliani, Donata Luiselli, Marco Sazzini, Paolo Garagnani, Chiara Pirazzini, Giuliani C, Bacalini MG, Sazzini M, Pirazzini C, Franceschi C, Garagnani P, and Luiselli D
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Aging ,Physiology ,Epidemiology ,Biology ,Environment ,HUMAN EVOLUTION ,Epigenesis, Genetic ,chemistry.chemical_compound ,Genetics ,Humans ,Epigenetics ,Genetic variability ,ADAPTATION ,Public Health, Environmental and Occupational Health ,Inheritance (genetic algorithm) ,Genetic Variation ,DNA ,DNA Methylation ,Adaptation, Physiological ,Diet ,chemistry ,Human evolution ,Evolutionary biology ,DNA methylation ,Adaptation - Abstract
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.
- Published
- 2014
42. The Mediterranean human population: an Anthropological Genetics perspective
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Donata Luiselli, Marco Sazzini, Stefania Sarno, Goffredo S and Dubinsky Z, Goffredo S. and Dubinsky Z., Sazzini M., Sarno S., and Luiselli D.
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Mediterranean climate ,Genetics ,education.field_of_study ,Human migration ,business.industry ,Population ,Population genetics ,Mediterranean Basin ,Genealogy ,Politics ,Mediterranean sea ,Geography ,Genetic structure ,Anthropological Genetics ,business ,education - Abstract
The Mediterranean Sea has long been one of the most important and crowded natural hubs for the expansion of human genes and cultures, representing a tri-continental crossroads for human migrations since the first dispersals of anatomically modern humans out of Africa. Both its ancient and modern history, with its amazing chronicle of biological and cultural transitions, has substantially influenced the current patchwork of anthropological types existing within this area. For a deep dissection of this patchwork, Anthropological Genetics combines information related to the population dynamics able to shape the genetic structure of human populations (i.e. geographical constraints, language, cultural, social and political barriers) to those provided by the powerful tools of molecular biology and population genetics. This comprehensive approach allows to trace genetic profiles of Mediterranean populations into the past to discover and reconstruct their origins and demographic histories, as well as their evolutionary relationships. Nevertheless, the genetic landscape of Mediterranean populations is far from being exhaustively drawn. Several Anthropological Genetics projects, basing on an even deeper genetic characterization of dense and accurately selected geographic samples, have been just launched and promise to shed new light on the pivotal role of the Mediterranean basin as a genetic barrier and/or a bridge between human groups characterized by different African, Near Eastern or European cultural backgrounds.
- Published
- 2014
43. Investigating the link between past adaptations and modern diseases: a nutrition-related perspective
- Author
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SAZZINI, MARCO, QUAGLIARIELLO, ANDREA, CHERUBINI, ANNA, DE FANTI, SARA, SPISNI, ENZO, LUISELLI, DONATA, Alyson Reid, Sazzini M., Quagliariello A., Cherubini A., De Fanti S., Spisni E., and Luiselli D.
- Abstract
A string of biological and cultural changes strongly related to the occupation of new environmental contexts has characterized the evolution of the human lineage, especially during the widespread colonization of non-African continents by anatomically modern humans. Therefore, geographically and temporally defined variation of selective pressures acting on the genomes of both H. sapiens ancestors and modern populations triggered genetic adaptations in response to local environments. In particular, necessity to cope with unprecedented nutritional landscapes prompted a number of biological shifts in many human groups, mainly related to the introduction of considerable modifications of their diets and of new challenges to their metabolism [1,2], contributing to influence a variety of traits, among which differential disease susceptibility of human populations due to possible maladaptive processes [3]. In fact, the rate of dietary changes dramatically increased in the very recent evolutionary history of our species, as a consequence of introduction of agricultural and pastoralist practices, of consumption of industrial refined foods and of ever-increasing globalization [4], thus potentially converting some adaptive traits into maladaptive ones. In accordance to this view, increasing discordance between our anciently determined biology and contemporary nutritional or cultural patterns is supposed to have contributed to the spread of several complex diseases, which may represent by-products of past adaptive events due to loci that have become detrimental in modern societies [5]. To test this hypothesis, we have investigated the genetic legacy of natural selection on a panel of about one hundred genes representative of the main players driving functional pathways associated to food digestion and energy balance, or which turned out to be altered in metabolic and nutrition-related diseases. Sequence data for human populations living in different biomes were collected from public databases and used, in combination with unpublished data on individuals affected by certain nutrition-related diseases, to explore patterns of variation at more than 100,000 single nucleotide variants and/or indels. Population differentiation analyses based on the calculation of pairwise Fst indices among genetically homogeneous clusters of populations and on their comparison with genome-wide Fst distributions pointed out a few genes unusually differentiated with respect to average genomic patterns. Haplotype structure and potential deviations from a neutral model of evolution were then investigated at these candidate regions by applying several neutrality tests and by performing calibrated coalescent simulations, to disentangle the interplay between natural selection, demographic events and local mutation/recombination rates in shaping the observed patterns of variation. This enabled to elucidate implications of loci responsible for past adaptive events in the examined diseases, contributing to explain their underlying mechanisms and present-day epidemiological patterns, as well as some of the evolutionary processes that made our genome prone to the side effects of modern environmental stimuli.
- Published
- 2014
44. Optimization of whole mitochondrial genome sequencing with Ion Personal Genome Machine (PGM) System
- Author
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DE FANTI, SARA, GIULIANI, CRISTINA, SAZZINI, MARCO, SEVINI, FEDERICA, VIANELLO, DARIO, FRANCESCHI, CLAUDIO, LUISELLI, DONATA, Iaquilano N., De Fanti S., Giuliani C., Sazzini M., Sevini F., Iaquilano N., Vianello D., Franceschi C., and Luiselli D.
- Abstract
The human mitochondrial DNA (mtDNA) phylogeny is an almost perfect molecular prototype for a non-recombining locus and knowledge on its variation has been extensively used in molecular anthropology and population genetics studies. Furthermore, its mode of inheritance, high mutation rate and high cellular copy number make this locus a primary choice also in the field of ancient DNA analysis, as well as in different contest such as biomedical research and diagnostic of mitochondrial disorders or human identification for forensic purposes. In the very last years, the study of mtDNA control region sequence and coding region single nucleotide polymorphisms have been gradually substituted by the investigation of variation at the whole mitochondrial genome, allowing analyses at a much higher resolution level and a deeper discrimination between haplogroups. In fact, high-throughput sequencing of whole mitochondrial genomes is now possible with lower costs with respect to those related to the traditional Sanger method thanks to Next Generation Sequencing (NGS) technologies. Among them, the Ion Personal Genome Machine (PGM, Life Technologies) is a new platform that uses an innovative method of sequencing. In fact, it does not use fluorescence or chemiluminescence, but measures the proton (H+) ions released during base incorporation. This new sequencing method allows to reduce times and costs of sequencing. The workflow, like other NGS, consists of four major steps: library construction, template preparation, sequencing and analysis. We develop a workflow for processing multiple samples in parallel through the preparation of barcoded libraries obtained by physical fragmentation of two long range PCR products with Bioruptor sonication system (Diagenode) at 200 base pairs reads. After equalization of single barcoded libraries in a pool the samples are subjected to an emulsion PCR reaction step. In this step, the library are attached to beads and amplified. During a step of enrichment only the beads that bind amplified template fragments are retrieved and these will be the template for the sequencing reaction. The sequencing technology is what really differentiates Ion Torrent platform; since optics are not required, the sequencing reaction is relatively fast and inexpensive. The obtained sequences are processed and aligned to the reference genome by means of the Ion Torrent suite and a dedicated bioinformatics tool was used to call single nucleotide and small insertion/deletion variants. We compared our results with those obtained by processing raw data via an ad hoc developed pipeline, as well as with those resulting from Sanger sequencing of the same samples to assess the reliability of the adopted protocol and sequencing technology.
- Published
- 2013
45. mtDNA variation in East Africa unravels the history of Afro-Asiatic groups
- Author
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Sara De Fanti, Stefania Sarno, Antonella Useli, Davide Pettener, Marco Sazzini, Manuela Cioffi, Alessio Boattini, Paolo Garagnani, Loredana Castrì, Donata Luiselli, Boattini A, Castrì L, Sarno S, Useli A, Cioffi M, Sazzini M, Garagnani P, De Fanti S, Pettener D, and Luiselli D
- Subjects
Population ,Pastoralism ,Black People ,Bantu languages ,Biology ,DNA, Mitochondrial ,Anthropology, Physical ,Evolution, Molecular ,Semitic ,genetic structure ,Cluster Analysis ,Humans ,Genetic variability ,education ,Omotic ,Phylogeny ,Language ,education.field_of_study ,Analysis of Variance ,Principal Component Analysis ,Ecology ,Phylum ,Genetic Variation ,Africa, Eastern ,Human evolution ,Haplotypes ,Cushitic ,Anthropology ,Afroasiatic languages ,Horn of Africa ,Genetic structure ,Anatomy - Abstract
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.
- Published
- 2013
46. Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine and Idarubicin
- Author
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Erica Simeone, Federica Cattina, Cristina Papayannidis, Maria Chiara Abbenante, Annalisa Astolfi, Ilaria Iacobucci, Marco Sazzini, Michele Baccarani, Emanuela Ottaviani, Michele Malagola, Filippo Gherlinzoni, Sarah Parisi, Serena Formica, Daniela Damiani, R Fanin, Domenico Russo, Michele Gottardi, Alberto Ferrari, Anna Candoni, Angela Michelutti, Annalisa Lonetti, Giovanni Martinelli, Iacobucci I., Lonetti A., Candoni A., Sazzini M., Papayannidis C., Formica S., Ottaviani E., Ferrari A., Michelutti A., Simeone E., Astolfi A., Abbenante M.C., Parisi S., Cattina F., Malagola M., Russo D., Damiani D., Gherlinzoni F., Gottardi M., Baccarani M., Fanin R., and Martinelli G.
- Subjects
Male ,Genotype ,Gemtuzumab ozogamicin ,CD33 ,Sialic Acid Binding Ig-like Lectin 3 ,Pharmacology ,Biology ,Antibodies, Monoclonal, Humanized ,NO ,Genetic Heterogeneity ,AML ,hemic and lymphatic diseases ,Genetics ,medicine ,Idarubicin ,Humans ,GO-FLAI ,DMET ,SNPs ,Cytarabine ,Myeloid leukemia ,Transporter ,Gemtuzumab ,Fludarabine ,Enzymes ,Drug metabolizing enzymes ,Leukemia, Myeloid, Acute ,Aminoglycosides ,Treatment Outcome ,Inactivation, Metabolic ,Molecular Medicine ,Female ,Neoplasm Recurrence, Local ,Vidarabine ,medicine.drug - Abstract
Genetic heterogeneity in drug-metabolizing enzyme/transporter (DMET) genes affects specific drug-related cancer phenotypes. To investigate the relationships between genetic variation and response to treatment in acute myeloid leukemia (AML), we genotyped 1931 variants on DMET genes in 94 CD33-positive AML patients enrolled in a phase III multicenter clinical trial combining Gemtuzumab-Ozogamicin (GO) with Fludarabine-Cytarabine-Idarubicin (FLAI) regimen, with the DMET Plus platform. Two ADH1A variants showed statistically significant differences (odds ratio (OR)=5.68, P=0.0006; OR=5.35, P=0.0009) in allele frequencies between patients in complete/partial remission and patients without response, two substitutions on CYP2E1 (OR=0.13, P=0.001; OR=0.09, P=0.003) and one on SLCO1B1 (OR=4.68, P=0.002) were found to differently influence liver toxicity, and two nucleotide changes on SULTB1 and SLC22A12 genes correlated with response to GO (OR=0.24, P=0.0009; OR=2.75, P=0.0029). Genetic variants were thus found for the first time to be potentially associated with differential response and toxicity in AML patients treated with a combination of GO-FLAI regimen.
- Published
- 2013
47. Variation patterns at nutrition-related genes: insight into human adaptations to dietary changes
- Author
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SAZZINI, MARCO, QUAGLIARIELLO, ANDREA, PAGANI, LUCA, DE FANTI, SARA, PETTENER, DAVIDE, LUISELLI, DONATA, Sazzini M., Quagliariello A., Pagani L., De Fanti S., Pettener D., and Luiselli D
- Abstract
Several dietary shifts have occurred in the human lineage accompanying transitions to high-quality diets, the adoption of meat eating, food processing and cooking, and facilitating the evolution of energetically expensive brains. Adaptations to new nutritional resources have thus strongly contributed to shape the genome of human ancestors and of H. sapiens, influencing a variety of traits, being often related to crucial biological/cultural innovations, and introducing novel challenges to human metabolism. The relatively recent human occupation of a vast range of environments, in which populations encountered ever new and demanding nutritional landscapes, further boosted the rate of these dietary changes, producing dramatic and still on-going modifications in human diets. Selective forces associated to food availability have thus varied over a geographical scale, driving adaptations in response to local environmental/cultural pressures, the latter having played a key role in the evolution of human diets, mainly through plants and animals domestication. Accordingly, adaptive genetic variants have been plausibly selected in human groups exposed to novel dietary environments during the last 60,000 years, even though cultural/dietary changes are ever-accelerating since the Neolithic Transition, leading to possible maladaptation in contemporary populations. Exploring the genetic bases of nutrition-related adaptations will thus enable to shed light not only on some of the main mechanisms that have shaped the human genome, but also on those contributing to common metabolic diseases affecting present-day societies. To detect signatures of these adaptations, genetic variation at more than 40 nutrition-related genes selected according to their major role in functional pathways associated to processing and digestion of food, or associated with metabolic diseases, was investigated in 14 populations from the phase I of the 1000 Genomes project. For this purpose, information about several thousands of SNPs was retrieved from sequence data and used to assess derived allele frequency, differentiation among the examined groups and genetic structure at the investigated loci. Different neutrality tests were used to shortlist the best candidate genes potentially responsible for moderate to strong patterns of dietary adaptation in the studied populations. Further understanding of the mechanisms of action of these genes promises to give new insight into the recent history of human adaptation and its implication on the epidemiology of metabolic diseases.
- Published
- 2013
48. Genome-culture interactions in the evolution of human taste
- Author
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RISSO, DAVIDE, DE FANTI, SARA, QUAGLIARIELLO, ANDREA, GIULIANI, CRISTINA, SAZZINI, MARCO, PETTENER, DAVIDE, Tofanelli S., Morini G., Risso D., De Fanti S., Quagliariello A., Giuliani C., Sazzini M., Tofanelli S., Morini G., and Pettener D
- Published
- 2013
49. Genetic variability of genes involved in Nutrition and Thermoregulation processes
- Author
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QUAGLIARIELLO, ANDREA, DE FANTI, SARA, GIULIANI, CRISTINA, SAZZINI, MARCO, LUISELLI, DONATA, Quagliariello A., De Fanti S., Giuliani C., Sazzini M., and Luiselli D.
- Abstract
Environmental changes, as well as evolution in cultural habits, are able to substantially affect populations’ allele frequencies: the well know case of selection on lactase persistence (LP) provides a good example for this assumption. Indeed, the process of dairy animal domestication seems to have positively selected different polymorphisms around the LCT gene, which are associated to LP[Enattah et al. 2002]. Several changes in dietary habits took place over human history since the introduction of meat consumption, the Neolithic transition, and the recent shift to an high caloric diet which led to a reversal of our dietary habits [Lindeberg 2012]. These new cultural habits have been established in such a recent time that it didn’t allow genomic adaptation to the new nutritional conditions. The mismatch between how our genome has adapted and the new dietary conditions is potentially at the basis of various common chronic diseases such as obesity, cardiovascular diseases, diabetes and cancer [Konner and Eaton 2010]. The interaction between the genome and the nutritional environment is obviously regulated not only by nutrition-related genes, but even by genes which modulate the perception of taste and thermoregulation, which rebalances the relation between temperature and the needed energy resources. According to these evidences, the aim of this study is to analyze, taking advantage from the 1000Genomes project phase I dataset, patterns of genetic variation at a set of genes, which have been selected for their involvement in nutritional processes, taste perception and thermogenesis, and to detect possible signs of selection at the investigated genomic regions. This in silico approach was used to detect the most interesting variants on the basis of their highest heterozygosity values among the examined European sub-populations. These results will subsequently drive experimental analyses of the most polymorphic genes on a Central-Southern Italian sample, collected according to a sampling strategy that takes into account the complex geographical and historical Italian background, as scheduled within the research activities of the EPIC project (PRIN2012).
- Published
- 2013
50. IL-23A, IL-23R, IL-17A and IL-17R polymorphisms in different psoriatic arthritis clinical manifestations in the northern Italian population
- Author
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Pierluigi Macchioni, Carlo Salvarani, Luigi Boiardi, Davide Nicoli, Marco Sazzini, Bruno Casali, Enrico Farnetti, Ilaria Chiarolanza, Paolo Garagnani, Maria Grazia Catanoso, Sara De Fanti, Donata Luiselli, Catanoso M.G., Boiardi L., Macchioni P., Garagnani P., Sazzini M., De Fanti S., Farnetti E., Casali B., Chiarolanza I., Nicoli D., Luiselli D., and Salvarani C.
- Subjects
Adult ,Male ,medicine.medical_specialty ,GENETIC VARIABILITY ,Spondyloarthropathy ,Immunology ,Arthritis ,Single-nucleotide polymorphism ,Gastroenterology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Psoriatic arthritis ,Rheumatology ,Gene Frequency ,Risk Factors ,Internal medicine ,medicine ,IL-17A ,Odds Ratio ,Immunology and Allergy ,Humans ,Genetic Predisposition to Disease ,Aged ,Arthritis, Psoriatic ,Case-Control Studies ,Chi-Square Distribution ,Female ,Haplotypes ,Interleukin-17 ,Interleukin-23 Subunit p19 ,Italy ,Logistic Models ,Middle Aged ,Phenotype ,Receptors, Interleukin ,Receptors, Interleukin-17 ,business.industry ,Psoriatic arthriti ,IL-23A and IL-23R genes ,Case-control study ,Enthesitis ,Odds ratio ,medicine.disease ,medicine.symptom ,business ,IL17-RA - Abstract
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 corr = 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.
- Published
- 2012
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