Sardinians genetic background explained by runs of homozygosity and genomic regions under positive selection

PLoS One. 2014 Mar 20;9(3):e91237. doi: 10.1371/journal.pone.0091237. eCollection 2014.


The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5)) when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing / genetics
  • Genome, Human / genetics*
  • Geography
  • Homozygote
  • Humans
  • Inbreeding
  • Italy
  • Mediterranean Sea
  • Polymorphism, Single Nucleotide / genetics
  • Principal Component Analysis
  • Selection, Genetic*
  • Software

Grant support

The Human Genetic Foundation (HuGeF) and the Compagnia di San Paolo of Turin (to M.G.) were the main supporter of this project. This study used data from the following grants: HYPERGENES project (funded by the Seventh Framework Programme FP7 - HEALTH-F4-2007-201550) and InterOmics an Italian Flagship project (funded b 1 y Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR) and Consiglio Nazionale delle Ricerche (CNR) Project PB.05 (to C.D.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.