European Journal of Human Genetics (2013) 21, 659–665; doi:10.1038/ejhg.2012.229; published online 19 December 2012

Genetic characterization of northeastern Italian population isolates in the context of broader European genetic diversity

Tõnu Esko1,2,3,28, Massimo Mezzavilla4,28, Mari Nelis1,3, Christelle Borel5, Tadeusz Debniak6, Eveliina Jakkula7, Antonio Julia8, Sena Karachanak9, Andrey Khrunin10, Peter Kisfali11, Veronika Krulisova12, Zita Aušrelé Kučinskiené13, Karola Rehnström14, Michela Traglia15, Liene Nikitina-Zake16, Fritz Zimprich17, Stylianos E Antonarakis5, Xavier Estivill18, Damjan Glavač19, Ivo Gut20, Janis Klovins16, Michael Krawczak21, Vaidutis Kučinskas13, Mark Lathrop22,23, Milan Macek12, Sara Marsal8, Thomas Meitinger24,25, Béla Melegh11, Svetlana Limborska10, Jan Lubinski6, Aarno Paolotie7,14, Stefan Schreiber21, Draga Toncheva9, Daniela Toniolo15, H-Erich Wichmann26,27, Alexander Zimprich17, Mait Metspalu2,3, Paolo Gasparini4,28, Andres Metspalu1,2,3,28 and Pio D'Adamo4,28

  1. 1Estonian Genome Center, University of Tartu, Tartu, Estonia
  2. 2Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
  3. 3Estonian Biocentre, Tartu, Estonia
  4. 4Medical Genetics, Department of Reproductive Sciences and Development, IRCCS-Burlo Garofolo, University of Trieste, Trieste, Italy
  5. 5Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
  6. 6International Hereditary Cancer Center and Department of Genetics, Pomeranian Medical University, Szczecin, Poland
  7. 7Institute for Molecular Medicine Finland (FIMM) and National Institute for Health and Welfare, Helsinki, Finland
  8. 8Unit of Investigation of Rheumatology, Vall d’Hebron Hospital, Barcelona, Spain
  9. 9Department of Medical Genetics, Medical University of Sofia, Sofia, Bulgaria
  10. 10Department of Molecular Bases of Human Genetics, Institute of Molecular Genetics, Russian Academy of Science, Moscow, Russia
  11. 11Department of Medical Genetics, University of Pécs, Pécs, Hungary
  12. 12Department of Biology and Medical Genetics, University Hospital Motol and Faculty of Medicine, Charles University Prague, Prague, Czech Republic
  13. 13Department of Human and Medical Genetics, Vilnius University, Vilnius, Lithuania
  14. 14Wellcome Trust Sanger Institute, Hinxton, UK
  15. 15Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy
  16. 16Latvian Biomedical Research and Study Center, Riga, Latvia
  17. 17Department of Clinical Neurology, Medical University of Vienna, Vienna, Austria
  18. 18Center for Genomic Regulation (CRG-UPF) and CIBERESP, Barcelona, Spain
  19. 19Department of Molecular Genetics, University of Ljubljana, Ljubljana, Slovenia
  20. 20Centre Nacional d’Anàlisis Genòmica, Barcelona, Spain
  21. 21PopGen Biobank, University Hospital Schleswig-Holstein, Campus Kiel, Germany
  22. 22Commissariat à l′Energie Atomique, Institut Genomique, Centre National de Génotypage, Evry, France
  23. 23McGill University and Genome Quebec Innovation Center, Montreal, Canada
  24. 24Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  25. 25Institute of Human Genetics, Technische Universität München, Klinikum rechts der Isar, Munich, Germany
  26. 26Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
  27. 27Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

Correspondence: Professor A Metspalu, Estonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia. Tel: +372 737 5066; Fax: +372 742 0286; E-mail:

28These authors contributed equally to this work.

Received 16 March 2012; Revised 21 August 2012; Accepted 4 September 2012
Advance online publication 19 December 2012



Population genetic studies on European populations have highlighted Italy as one of genetically most diverse regions. This is possibly due to the country’s complex demographic history and large variability in terrain throughout the territory. This is the reason why Italy is enriched for population isolates, Sardinia being the best-known example. As the population isolates have a great potential in disease-causing genetic variants identification, we aimed to genetically characterize a region from northeastern Italy, which is known for isolated communities. Total of 1310 samples, collected from six geographically isolated villages, were genotyped at >145000 single-nucleotide polymorphism positions. Newly genotyped data were analyzed jointly with the available genome-wide data sets of individuals of European descent, including several population isolates. Despite the linguistic differences and geographical isolation the village populations still show the greatest genetic similarity to other Italian samples. The genetic isolation and small effective population size of the village populations is manifested by higher levels of genomic homozygosity and elevated linkage disequilibrium. These estimates become even more striking when the detected substructure is taken into account. The observed level of genetic isolation in Friuli-Venezia Giulia region is more extreme according to several measures of isolation compared with Sardinians, French Basques and northern Finns, thus proving the status of an isolate.


population genetics; isolated population; genetic distance