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Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations.
Xue, Yali; Mezzavilla, Massimo; Haber, Marc; McCarthy, Shane; Chen, Yuan; Narasimhan, Vagheesh; Gilly, Arthur; Ayub, Qasim; Colonna, Vincenza; Southam, Lorraine; Finan, Christopher; Massaia, Andrea; Chheda, Himanshu; Palta, Priit; Ritchie, Graham; Asimit, Jennifer; Dedoussis, George; Gasparini, Paolo; Palotie, Aarno; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Wilson, James F; Durbin, Richard; Tyler-Smith, Chris; Zeggini, Eleftheria.
Afiliação
  • Xue Y; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Mezzavilla M; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Haber M; Institute for Maternal and Child Health, IRCCS Burlo Garofolo, University of Trieste, 34137 Trieste, Italy.
  • McCarthy S; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Chen Y; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Narasimhan V; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Gilly A; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Ayub Q; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Colonna V; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Southam L; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Finan C; Consiglio Nazionale delle Ricerche, Istituto di Genetica e Biofisica 'Adriano Buzzati-Traverso', via Pietro Castellino 111, 80131 Napoli, Italy.
  • Massaia A; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Chheda H; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Palta P; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Ritchie G; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Asimit J; National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
  • Dedoussis G; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, 00290 Helsinki, Finland.
  • Gasparini P; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, 00290 Helsinki, Finland.
  • Palotie A; Estonian Genome Center, University of Tartu, 23B Riia Street, 51010 Tartu, Estonia.
  • Ripatti S; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Soranzo N; European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
  • Toniolo D; MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
  • Wilson JF; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Durbin R; Department of Nutrition and Dietetics, Harokopio University Athens, Athens, Eleftheriou Venizelou 70, Kallithea 176 76, Greece.
  • Tyler-Smith C; Medical Genetics, DSM, University of Trieste and IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Burlo Garofolo Children Hospital, Via dell'Istria, 65, 34137 Trieste, Italy.
  • Zeggini E; The Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
Nat Commun ; 8: 15927, 2017 06 23.
Article em En | MEDLINE | ID: mdl-28643794
The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-genome sequences from eight European isolates and two matched general populations, together with published data from the 1000 Genomes Project and UK10K. Sequencing data give deeper and richer insights into population demography and genetic characteristics than genotype-chip data, distinguishing related populations more effectively and allowing their functional variants to be studied more fully. We demonstrate relaxation of purifying selection in the isolates, leading to enrichment of rare and low-frequency functional variants, using novel statistics, DVxy and SVxy. We also develop an isolation-index (Isx) that predicts the overall level of such key genetic characteristics and can thus help guide population choice in future complex-trait association studies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Humano / População Branca Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Humano / População Branca Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article