A bird's-eye view of Italian genomic variation through whole-genome sequencing

Anno:

2019

A bird's-eye view of Italian genomic variation through whole-genome sequencing

Cocca M1, Barbieri C2, Concas MP1, Robino A1, Brumat M3, Gandin I3, Trudu M4, Sala CF2, Vuckovic D5, Girotto G1,3, Matullo G6,7, Polasek O8, Kolčić I8, Gasparini P1,3, Soranzo N5, Toniolo D2, Mezzavilla M9.

Eur J Hum Genet. 2019 Nov 29. doi: 10.1038/s41431-019-0551-x. [Epub ahead of print] PMID: 31784700

Author information

Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
Molecular Genetics of Renal Disorders Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK.
Department of Medical Sciences, University of Turin, Turin, Italy.
Italian Institute for Genomic Medicine (IIGM), Turin, Italy.
Public Health, University of Split, Split, Croatia.
Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. massimo.mezzavilla@burlo.trieste.it.

Abstract

The genomic variation of the Italian peninsula populations is currently under characterised: the only Italian whole-genome reference is represented by the Tuscans from the 1000 Genome Project. To address this issue, we sequenced a total of 947 Italian samples from three different geographical areas. First, we defined a new Italian Genome Reference Panel (IGRP1.0) for imputation, which improved imputation accuracy, especially for rare variants, and we tested it by GWAS analysis on red blood traits. Furthermore, we extended the catalogue of genetic variation investigating the level of population structure, the pattern of natural selection, the distribution of deleterious variants and occurrence of human knockouts (HKOs). Overall the results demonstrate a high level of genomic differentiation between cohorts, different signatures of natural selection and a distinctive distribution of deleterious variants and HKOs, confirming the necessity of distinct genome references for the Italian population.