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Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers

  1. Author:
    Im, K. M.
    Kirchhoff, T.
    Wang, X. S.
    Green, T.
    Chow, C. Y.
    Vijai, J.
    Korn, J.
    Gaudet, M. M.
    Fredericksen, Z.
    Pankratz, V. S.
    Guiducci, C.
    Crenshaw, A.
    McGuffog, L.
    Kartsonaki, C.
    Morrison, J.
    Healey, S.
    Sinilnikova, O. M.
    Mai, P. L.
    Greene, M. H.
    Piedmonte, M.
    Rubinstein, W. S.
    Hogervorst, F. B.
    Rookus, M. A.
    Collee, J. M.
    Hoogerbrugge, N.
    van Asperen, C. J.
    Meijers-Heijboer, H. E. J.
    van Roozendaal, C. E.
    Caldes, T.
    Perez-Segura, P.
    Jakubowska, A.
    Lubinski, J.
    Huzarski, T.
    Blecharz, P.
    Nevanlinna, H.
    Aittomaki, K.
    Lazaro, C.
    Blanco, I.
    Barkardottir, R. B.
    Montagna, M.
    D'Andrea, E.
    Devilee, P.
    Olopade, O. I.
    Neuhausen, S. L.
    Peissel, B.
    Bonanni, B.
    Peterlongo, P.
    Singer, C. F.
    Rennert, G.
    Lejbkowicz, F.
    Andrulis, I. L.
    Glendon, G.
    Ozcelik, H.
    Tol, A. E.
    Caligo, M. A.
    Beattie, M. S.
    Chan, S.
    Domchek, S. M.
    Nathanson, K. L.
    Rebbeck, T. R.
    Phelan, C.
    Narod, S.
    John, E. M.
    Hopper, J. L.
    Buys, S. S.
    Daly, M. B.
    Southey, M. C.
    Terry, M. B.
    Tung, N.
    Hansen, T. V. O.
    Osorio, A.
    Benitez, J.
    Duran, M.
    Weitzel, J. N.
    Garber, J.
    Hamann, U.
    Peock, S.
    Cook, M.
    Oliver, C. T.
    Frost, D.
    Platte, R.
    Evans, D. G.
    Eeles, R.
    Izatt, L.
    Paterson, J.
    Brewer, C.
    Hodgson, S.
    Morrison, P. J.
    Porteous, M.
    Walker, L.
    Rogers, M. T.
    Side, L. E.
    Godwin, A. K.
    Schmutzler, R. K.
    Wappenschmidt, B.
    Laitman, Y.
    Meindl, A.
    Deissler, H.
    Varon-Mateeva, R.
    Preisler-Adams, S.
    Kast, K.
    Venat-Bouvet, L.
    Stoppa-Lyonnet, D.
    Chenevix-Trench, G.
    Easton, D. F.
    Klein, R. J.
    Daly, M. J.
    Friedman, E.
    Dean, M.
    Clark, A. G.
    Altshuler, D. M.
    Antoniou, A. C.
    Couch, F. J.
    Offit, K.
    Gold, B.

  2. Author Address

    [Gold, B] NCI, Frederick, MD 21702 USA. [Im, KM; Dean, M; Gold, B] NCI, Ctr Canc Res, Canc Inflammat Program, Human Genet Sect, Frederick, MD 21701 USA. [Kirchhoff, T; Vijai, J; Klein, RJ; Offit, K] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, Dept Med, Program Canc Prevent & Populat Res,Program Canc P, New York, NY 10021 USA. [Wang, XS; Fredericksen, Z; Pankratz, VS; Couch, FJ] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Green, T; Korn, J; Guiducci, C; Crenshaw, A; Collee, JM; Montagna, M] Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA USA. [Green, T; Korn, J; Guiducci, C; Crenshaw, A; Daly, MJ; Altshuler, DM] Harvard Univ, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02138 USA. [Green, T; Korn, J; Guiducci, C; Crenshaw, A; Daly, MJ; Altshuler, DM] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Human Genet Res, Boston, MA 02114 USA. [Chow, CY; Clark, AG] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA. [Gaudet, MM] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [McGuffog, L; Kartsonaki, C; Morrison, J] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Healey, S; Chenevix-Trench, G; Antoniou, AC] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Sinilnikova, OM] Ctr Hosp Univ Lyon, Unite Mixte Genet Constitut Canc Frequents, Ctr Lyon Berard, Lyon, France. [Sinilnikova, OM] Univ Lyon, Ctr Leon Berard, Lyon, France. [Mai, PL; Greene, MH] NCI, Clin Genet Branch, Rockville, MD USA. [Piedmonte, M] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Rubinstein, WS] NorthShore Univ Hlth Syst, Evanston, IL USA. [Hogervorst, FB] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [Rookus, MA] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, JM] Erasmus Univ, Dept Clin Genet, Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Hoogerbrugge, N] Radboud Univ Nijmegen, Hereditary Canc Clin, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Meijers-Heijboer, HEJ] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Leiden, Netherlands. [van Roozendaal, CE] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Caldes, T; Perez-Segura, P] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Jakubowska, A; Lubinski, J; Huzarski, T] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland. [Blecharz, P] Maria Sklodowska Curie Mem Inst Oncol, Ctr Oncol, Krakow, Poland. [Nevanlinna, H] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Aittomaki, K] Univ Helsinki, Cent Hosp, Dept Clin Genet, FIN-00290 Helsinki, Finland. [Lazaro, C; Blanco, I] Catalan Inst Oncol IDIBELL, Hereditary Canc Program, Barcelona, Spain. [Barkardottir, RB] Landspitali LSH, Dept Pathol, Reykjavik, Iceland. [Barkardottir, RB] Univ Iceland, Fac Med, Reykjavik, Iceland. [Montagna, M; D'Andrea, E] IRCCS, Immunol & Mol Oncol Unit, Ist Oncol Veneto IOV, Padua, Italy. [D'Andrea, E] Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. Peter MacCallum Canc Ctr, Kathleen Cuningham Fdn Consortium Res Familial Br, Melbourne, Vic, Australia. [Devilee, P] Leiden Univ, Dept Human Genet & Pathol, Med Ctr, Leiden, Netherlands. [Olopade, OI] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Dept Med, Chicago, IL 60637 USA. [Neuhausen, SL] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Peissel, B] Fdn IRCCS Ist Nazl Tumori INT, Unit Med Genet, Dept Prevent & Predict Med, Milan, Italy. [Bonanni, B] IEO, Div Canc Prevent & Genet, Milan, Italy. [Peterlongo, P] Fdn IRCCS Ist Nazl Tumori INT, Unit Genet Susceptibil Canc, Dept Expt Oncol & Mol Med, Milan, Italy. [Peterlongo, P] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Singer, CF] Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria. [Singer, CF] Univ Vienna, Comprehens Canc Med Ctr, Vienna, Austria. [Rennert, G; Lejbkowicz, F] Carmel Hosp, CHS Natl Canc Control Ctr, Haifa, Israel. [Andrulis, IL; Ozcelik, H] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Andrulis, IL; Glendon, G; Ozcelik, H] Technion Israel Inst Technol, Fac Med, Haifa, Israel. [Andrulis, IL; Ozcelik, H] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, IL] Univ Toronto, Genet Network, Toronto, ON, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Andrulis, IL] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Toland, AE] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Caligo, MA] Univ Pisa, Sect Genet Oncol, Dept Lab Med, Pisa, Italy. Santa Chiara Univ Hosp, Pisa, Italy. Lund Univ, Dept Oncol, Lund, Sweden. [Beattie, MS] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Chan, S] Univ Calif San Francisco, Canc Risk Program, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. Univ Cambridge, Dept Oncol, Cambridge, England. [Domchek, SM; Nathanson, KL; Rebbeck, TR] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Phelan, C] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Narod, S] Womens Coll Res Inst, Toronto, ON, Canada. [John, EM] Canc Prevent Inst Calif, Fremont, CA USA. [Hopper, JL] Univ Melbourne, Ctr Genet Epidemiol, Melbourne, Vic 3010, Australia. [Buys, SS] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Daly, MB] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Terry, MB] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Tung, N] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Hansen, TVO] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Osorio, A] Copenhagen Univ Hosp, Dept Clin Biochem, Rigshosp, Copenhagen, Denmark. [Osorio, A] Spanish Natl Canc Res Ctr, Human Genet Grp, Canc Genet Programme, Madrid, Spain. [Osorio, A; Benitez, J] Spanish Network Rare Dis CIBERER, Madrid, Spain. [Benitez, J] Spanish Natl Canc Res Ctr, Human Genet Grp & Genotyping Unit, Human Canc Genet Programme, Madrid, Spain. [Duran, M] Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain. [Weitzel, JN] City Hope Canc Ctr, Div Clin Canc Genet, Duarte, CA USA. [Garber, J] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hamann, U] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. [Evans, DG] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, R] Inst Canc Res, Oncogenet Team, Surrey, England. [Izatt, L] Royal Marsden NHS Fdn Trust, Surrey, England. [Paterson, J] Guys & St Thomas NHS Fdn Trust, London, England. [Brewer, C] Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England. [Hodgson, S] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Morrison, PJ] Univ London, Dept Clin Genet, London, England. [Porteous, M] Belfast City Hosp, No Ireland Reg Genet Ctr, Belfast BT9 7AD, Antrim, North Ireland. [Walker, L] Western Gen Hosp, SE Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland. [Rogers, MT] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England. [Side, LE] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF4 4XW, S Glam, Wales. [Godwin, AK] Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London WC1N 3JH, England. [Schmutzler, RK; Wappenschmidt, B] Univ Kansas, Med Ctr, Dept Pathol & Lab, Kansas City, KS 66103 USA. [Venat-Bouvet, L] Univ Hosp Cologne, Cologne, Germany. [Stoppa-Lyonnet, D] Ctr Hosp Univ Dupuytren, Dept Med Oncol, Limoges, France. [Laitman, Y; Friedman, E] Univ Paris 05, INSERM, U509, Serv Genet Oncol,Inst Curie, Paris, France. [Meindl, A] Chaim Sheba Med Ctr, Susan Levy Gertner Oncogenet Unit, Inst Genet, IL-52621 Tel Hashomer, Israel. [Deissler, H] Tech Univ Munich, Munich, Germany. [Varon-Mateeva, R] Univ Hosp Ulm, Ulm, Germany. [Preisler-Adams, S] Charite Campus Virchow Klinikum, Inst Human Genet, Berlin, Germany. [Kast, K] Univ Munster, Inst Human Genet, D-4400 Munster, Germany. [Gold, B] Tech Univ Dresden, Dept Obstet & Gynaecol, Univ Hosp Carl Gustav, Dresden, Germany.;Gold, B (reprint author), NCI, Box B,Boyles St Ft Detrick, Frederick, MD 21702 USA;golda@mail.nih.gov
    1. Year: 2011
    2. Date: Nov
  2. Journal: Human Genetics
    1. 130
    2. 5
    3. Pages: 685-699
  4. Type of Article: Article
  5. ISSN: 0340-6717
  1. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1007/s00439-011-1003-z
  3. View record in Web of Science®
  4. WOS: 000295939900009

Library Notes

  1. Fiscal Year: FY2011-2012
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