title: Complex interplay between neutral and adaptive evolution shaped differential genomic background and disease susceptibility along the Italian peninsula.
abstract: 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.
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Marco
authors: M
authors: Sazzini
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Guido Alberto
authors: GA
authors: Gnecchi Ruscone
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Cristina
authors: C
authors: Giuliani
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Stefania
authors: S
authors: Sarno
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Andrea
authors: A
authors: Quagliariello
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Sara
authors: S
authors: De Fanti
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Alessio
authors: A
authors: Boattini
authors: Centre for Biomedical Research and Technologies, Italian Auxologic Institute, IRCCS, Milano, Italy.
authors: Davide
authors: D
authors: Gentilini
authors: Department of Medical Sciences, University of Torino and Human Genetics Foundation, Torino, Italy.
authors: Giovanni
authors: G
authors: Fiorito
authors: Rheumatology Unit, Arcispedale Santa Maria Nuova Hospital, IRCCS, Reggio Emilia, Italy.
authors: Mariagrazia
authors: M
authors: Catanoso
authors: Rheumatology Unit, Arcispedale Santa Maria Nuova Hospital, IRCCS, Reggio Emilia, Italy.
authors: Luigi
authors: L
authors: Boiardi
authors: Allergy and Advanced Biotechnologies Unit, Arcispedale Santa Maria Nuova Hospital, IRCCS, Reggio Emilia, Italy.
authors: Stefania
authors: S
authors: Croci
authors: Rheumatology Unit, Arcispedale Santa Maria Nuova Hospital, IRCCS, Reggio Emilia, Italy.
authors: Pierluigi
authors: P
authors: Macchioni
authors: Center for Applied Biomedical Research, S. Orsola-Malpighi University Hospital, Bologna, Italy.
authors: Vilma
authors: V
authors: Mantovani
authors: Centre for Biomedical Research and Technologies, Italian Auxologic Institute, IRCCS, Milano, Italy.
authors: Anna Maria
authors: AM
authors: Di Blasio
authors: Department of Medical Sciences, University of Torino and Human Genetics Foundation, Torino, Italy.
authors: Giuseppe
authors: G
authors: Matullo
authors: Rheumatology Unit, Arcispedale Santa Maria Nuova Hospital, IRCCS, Reggio Emilia, Italy.
authors: Carlo
authors: C
authors: Salvarani
authors: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors: Claudio
authors: C
authors: Franceschi
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Davide
authors: D
authors: Pettener
authors: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors: Paolo
authors: P
authors: Garagnani
authors: Laboratory of Molecular Anthropology and Centre for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.
authors: Donata
authors: D
authors: Luiselli
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D001327:Autoimmune Diseases / Q000208:ethnology / Q000235:genetics*; D005075:Biological Evolution; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D004198:Disease Susceptibility; D051456:Gene Flow; D014644:Genetic Variation; D005828:Genetics, Population / Q000706:statistics & numerical data*; D015894:Genome, Human; D006239:Haplotypes; D063426:Human Migration; D006801:Humans; D007558:Italy; D010802:Phylogeny; D012641:Selection, Genetic; D044465:White People