Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-05-20

AUTHORS

Kate M. Im, Tomas Kirchhoff, Xianshu Wang, Todd Green, Clement Y. Chow, Joseph Vijai, Joshua Korn, Mia M. Gaudet, Zachary Fredericksen, V. Shane Pankratz, Candace Guiducci, Andrew Crenshaw, Lesley McGuffog, Christiana Kartsonaki, Jonathan Morrison, Sue Healey, Olga M. Sinilnikova, Phuong L. Mai, Mark H. Greene, Marion Piedmonte, Wendy S. Rubinstein, HEBON, Frans B. Hogervorst, Matti A. Rookus, J. Margriet Collée, Nicoline Hoogerbrugge, Christi J. van Asperen, Hanne E. J. Meijers-Heijboer, Cees E. Van Roozendaal, Trinidad Caldes, Pedro Perez-Segura, Anna Jakubowska, Jan Lubinski, Tomasz Huzarski, Paweł Blecharz, Heli Nevanlinna, Kristiina Aittomäki, Conxi Lazaro, Ignacio Blanco, Rosa B. Barkardottir, Marco Montagna, Emma D’Andrea, kConFab, Peter Devilee, Olufunmilayo I. Olopade, Susan L. Neuhausen, Bernard Peissel, Bernardo Bonanni, Paolo Peterlongo, Christian F. Singer, Gad Rennert, Flavio Lejbkowicz, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Ontario Cancer Genetics Network, Amanda Ewart Toland, Maria Adelaide Caligo, SWE-BRCA, Mary S. Beattie, Salina Chan, UKFOCR, Susan M. Domchek, Katherine L. Nathanson, Timothy R. Rebbeck, Catherine Phelan, Steven Narod, Esther M. John, John L. Hopper, Saundra S. Buys, Mary B. Daly, Melissa C. Southey, Mary-Beth Terry, Nadine Tung, Thomas v. O. Hansen, Ana Osorio, Javier Benitez, Mercedes Durán, Jeffrey N. Weitzel, Judy Garber, Ute Hamann, EMBRACE, Susan Peock, Margaret Cook, Clare T. Oliver, Debra Frost, Radka Platte, D. Gareth Evans, Ros Eeles, Louise Izatt, Joan Paterson, Carole Brewer, Shirley Hodgson, Patrick J. Morrison, Mary Porteous, Lisa Walker, Mark T. Rogers, Lucy E. Side, Andrew K. Godwin, Rita K. Schmutzler, Barbara Wappenschmidt, Yael Laitman, Alfons Meindl, Helmut Deissler, Raymonda Varon-Mateeva, Sabine Preisler-Adams, Karin Kast, Laurence Venat-Bouvet, Dominique Stoppa-Lyonnet, Georgia Chenevix-Trench, Douglas F. Easton, Robert J. Klein, Mark J. Daly, Eitan Friedman, Michael Dean, Andrew G. Clark, David M. Altshuler, Antonis C. Antoniou, Fergus J. Couch, Kenneth Offit, Bert Gold

ABSTRACT

Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele frequencies in the surrounding genomic regions reflect adaptive or balancing selection. Such proposals predict long-range linkage disequilibrium (LD) resulting from a selective sweep, although genetic drift in a founder population may also act to create long-distance LD. To date, few studies have used the tools of statistical genomics to examine the likelihood of long-range LD at a deleterious locus in a population that faced a genetic bottleneck. We studied the genotypes of hundreds of women from a large international consortium of BRCA1 and BRCA2 mutation carriers and found that AJ women exhibited long-range haplotypes compared to CNJ women. More than 50% of the AJ chromosomes with the BRCA1 185delAG mutation share an identical 2.1 Mb haplotype and nearly 16% of AJ chromosomes carrying the BRCA2 6174delT mutation share a 1.4 Mb haplotype. Simulations based on the best inference of Ashkenazi population demography indicate that long-range haplotypes are expected in the context of a genome-wide survey. Our results are consistent with the hypothesis that a local bottleneck effect from population size constriction events could by chance have resulted in the large haplotype blocks observed at high frequency in the BRCA1 and BRCA2 regions of Ashkenazi Jews. More... »

PAGES

685-699

Journal

TITLE

Human Genetics

ISSUE

5

VOLUME

130

Author Affiliations

  • Center for Cancer Research, Cancer Inflammation Program, Human Genetics Section, National Cancer Institute, Frederick, MD, USA
  • Clinical Genetics Service, Department of Medicine, Program in Cancer Prevention and Population Research, Program in Cancer Biology and Genetics (RJK), Memorial Sloan-Kettering Cancer Center, New York, NY, USA
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • Department of Molecular Biology, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
  • Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA
  • Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
  • Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • Genetics and Population Health Division, Queensland Institute of Medical Research, Brisbane, Australia
  • Centre Léon Bérard, Université de Lyon, Lyon, France
  • Clinical Genetics Branch, National Cancer Institute, Rockville, MD, USA
  • GOG Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA
  • NorthShore University Health System, Evanston, IL, USA
  • Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, The Netherlands
  • Hereditary Cancer Clinic, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
  • Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
  • Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands
  • Department of Clinical Genetics, University Medical Center, Maastricht, The Netherlands
  • Molecular Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain
  • International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Kraków, Poland
  • Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
  • Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland
  • Hereditary Cancer Program, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain
  • Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  • Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV, IRCCS, Padua, Italy
  • Department of Oncology and Surgical Sciences, University of Padua, Padua, Italy
  • Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia
  • Department of Human Genetics and Pathology, Leiden University Medical Center, Leiden, The Netherlands
  • Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago Medical Center, Chicago, IL, USA
  • Department of Population Sciences, The Beckman Research Institute of the City of Hope, Duarte, CA, USA
  • Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy
  • Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy
  • IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy
  • Comprehensive Cancer Medical Center, University of Vienna, Vienna, Austria
  • CHS National Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel
  • Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
  • Cancer Care Ontario, University of Toronto, Toronto, ON, Canada
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  • Department of Molecular Virology Immunology, and Medical Genetics and Internal Medicine, The Ohio State University, Columbus, OH, USA
  • Section of Genetic Oncology, Department of Laboratory Medicine, University of Pisa and Santa Chiara University Hospital, Pisa, Italy
  • Department of Oncology, Lund University, Lund, Sweden
  • Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
  • Cancer Risk Program, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
  • Department of Oncology, University of Cambridge, Cambridge, UK
  • Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
  • Moffitt Cancer Center, Tampa, FL, USA
  • Women’s College Research Institute, Toronto, ON, Canada
  • Cancer Prevention Institute of California, Fremont, CA, USA
  • Centre for Genetic Epidemiology, University of Melbourne, Victoria, Australia
  • Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
  • Fox Chase Cancer Center, Philadelphia, PA, USA
  • Department of Pathology, The University of Melbourne, 3010, Victoria, Australia
  • Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
  • Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Brookline Avenue, Boston, MA, USA
  • Genomic Medicine, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • Spanish Network on Rare Diseases (CIBERER), Madrid, Spain
  • Human Genetics Group and Genotyping Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, Madrid, Spain
  • Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain
  • Division of Clinical Cancer Genetics, City of Hope Cancer Center, Duarte, CA, USA
  • Dana Farber Cancer Institute, Harvard University, Boston, MA, USA
  • Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
  • Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  • Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK
  • Clinical Genetics, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK
  • Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK
  • Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK
  • Clinical Genetics Department, St Georges Hospital, University of London, London, UK
  • Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, UK
  • South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK
  • Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK
  • All Wales Medical Genetics Services, University Hospital of Wales, Cardiff, UK
  • North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, UK
  • Department of Pathology and Laboratory, University of Kansas Medical Center, Kansas City, KS, USA
  • University Hospital of Cologne, Cologne, Germany
  • The Susan Levy Gertner Oncogenetics unit, Institute of Genetics, Sheba Medical Center, Tel Hashomer, Israel
  • Technical University Munich, Munich, Germany
  • University Hospital Ulm, Ulm, Germany
  • Institute of Human Genetics, Charite Campus Virchow Klinikum, Berlin, Germany
  • Institute of Human Genetics, University of Münster, Münster, Germany
  • Department of Gynaecology and Obstetrics, University Hospital Carl Gustav, Technical University Dresden, Dresden, Germany
  • Department of Medical Oncology, Centre Hospitalier Universitaire Dupuytren, Limoges, France
  • INSERM U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes, Paris, France
  • NCI-Frederick, Boyles Street Fort Detrick, Box B, 21702, Frederick, MD, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00439-011-1003-z

    DOI

    http://dx.doi.org/10.1007/s00439-011-1003-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1023400874

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/21597964


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