Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.

The island of Sardinia shows a unique high incidence of several autoimmune diseases with multifactorial inheritance, particularly type 1 diabetes and multiple sclerosis. The prior knowledge of the genetic structure of this population is fundamental to establish the optimal design for association stu...

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Main Authors: Daniela Contu, Laura Morelli, Federico Santoni, Jamie W Foster, Paolo Francalacci, Francesco Cucca
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2174525?pdf=render
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spelling doaj-67e271a5b329426aa9f2df46efa967502020-11-25T02:36:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0131e143010.1371/journal.pone.0001430Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.Daniela ContuLaura MorelliFederico SantoniJamie W FosterPaolo FrancalacciFrancesco CuccaThe island of Sardinia shows a unique high incidence of several autoimmune diseases with multifactorial inheritance, particularly type 1 diabetes and multiple sclerosis. The prior knowledge of the genetic structure of this population is fundamental to establish the optimal design for association studies in these diseases. Previous work suggested that the Sardinians are a relatively homogenous population, but some reports were contradictory and data were largely based on variants subject to selection. For an unbiased assessment of genetic structure, we studied a combination of neutral Y-chromosome variants, 21 biallelic and 8 short tandem repeats (STRs) in 930 Sardinian males. We found a high degree of interindividual variation but a homogenous distribution of the detected variability in samples from three separate regions of the island. One haplogroup, I-M26, is rare or absent outside Sardinia and is very common (0.37 frequency) throughout the island, consistent with a founder effect. A Bayesian full likelihood analysis (BATWING) indicated that the time from the most recent common ancestor (TMRCA) of I-M26, was 21.0 (16.0-25.5) thousand years ago (KYA) and that the population began to expand 14.0 (7.8-22.0) KYA. These results suggest a largely pre-Neolithic settlement of the island with little subsequent gene flow from outside populations. Consequently, Sardinia is an especially attractive venue for case-control genome wide association scans in common multifactorial diseases. Concomitantly, the high degree of interindividual variation in the current population facilitates fine mapping efforts to pinpoint the aetiologic polymorphisms.http://europepmc.org/articles/PMC2174525?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Daniela Contu
Laura Morelli
Federico Santoni
Jamie W Foster
Paolo Francalacci
Francesco Cucca
spellingShingle Daniela Contu
Laura Morelli
Federico Santoni
Jamie W Foster
Paolo Francalacci
Francesco Cucca
Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.
PLoS ONE
author_facet Daniela Contu
Laura Morelli
Federico Santoni
Jamie W Foster
Paolo Francalacci
Francesco Cucca
author_sort Daniela Contu
title Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.
title_short Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.
title_full Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.
title_fullStr Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.
title_full_unstemmed Y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse Sardinian population: inference for association scans.
title_sort y-chromosome based evidence for pre-neolithic origin of the genetically homogeneous but diverse sardinian population: inference for association scans.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2008-01-01
description The island of Sardinia shows a unique high incidence of several autoimmune diseases with multifactorial inheritance, particularly type 1 diabetes and multiple sclerosis. The prior knowledge of the genetic structure of this population is fundamental to establish the optimal design for association studies in these diseases. Previous work suggested that the Sardinians are a relatively homogenous population, but some reports were contradictory and data were largely based on variants subject to selection. For an unbiased assessment of genetic structure, we studied a combination of neutral Y-chromosome variants, 21 biallelic and 8 short tandem repeats (STRs) in 930 Sardinian males. We found a high degree of interindividual variation but a homogenous distribution of the detected variability in samples from three separate regions of the island. One haplogroup, I-M26, is rare or absent outside Sardinia and is very common (0.37 frequency) throughout the island, consistent with a founder effect. A Bayesian full likelihood analysis (BATWING) indicated that the time from the most recent common ancestor (TMRCA) of I-M26, was 21.0 (16.0-25.5) thousand years ago (KYA) and that the population began to expand 14.0 (7.8-22.0) KYA. These results suggest a largely pre-Neolithic settlement of the island with little subsequent gene flow from outside populations. Consequently, Sardinia is an especially attractive venue for case-control genome wide association scans in common multifactorial diseases. Concomitantly, the high degree of interindividual variation in the current population facilitates fine mapping efforts to pinpoint the aetiologic polymorphisms.
url http://europepmc.org/articles/PMC2174525?pdf=render
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