Im, Kate M., Kirchhoff, Tomas ORCID: 0000-0002-9055-2364, Wang, Xianshu, Green, Todd, Chow, Clement Y., Vijai, Joseph, Korn, Joshua, Gaudet, Mia M., Fredericksen, Zachary, Pankratz, V. Shane, Guiducci, Candace, Crenshaw, Andrew, McGuffog, Lesley, Kartsonaki, Christiana, Morrison, Jonathan, Healey, Sue, Sinilnikova, Olga M., Mai, Phuong L., Greene, Mark H., Piedmonte, Marion, Rubinstein, Wendy S., Hogervorst, Frans B., Rookus, Matti A., Collee, J. Margriet, Hoogerbrugge, Nicoline ORCID: 0000-0003-2393-8141, van Asperen, Christi J., Meijers-Heijboer, Hanne E. J., van Roozendaal, Cees E., Caldes, Trinidad, Perez-Segura, Pedro, Jakubowska, Anna ORCID: 0000-0002-5650-0501, Lubinski, Jan ORCID: 0000-0003-2931-3003, Huzarski, Tomasz ORCID: 0000-0003-3857-4854, Blecharz, Pawel ORCID: 0000-0001-5310-0054, Nevanlinna, Heli ORCID: 0000-0002-0916-2976, Aittomaki, Kristiina, Lazaro, Conxi, Blanco, Ignacio ORCID: 0000-0002-7414-7481, Barkardottir, Rosa B., Montagna, Marco, D'Andrea, Emma, Devilee, Peter, Olopade, Olufunmilayo I., Neuhausen, Susan L., Peissel, Bernard ORCID: 0000-0001-9233-3571, Bonanni, Bernardo, Peterlongo, Paolo ORCID: 0000-0001-6951-6855, Singer, Christian F., Rennert, Gad, Lejbkowicz, Flavio, Andrulis, Irene L., Glendon, Gord, Ozcelik, Hilmi, Toland, Amanda Ewart, Caligo, Maria Adelaide, Beattie, Mary S., Chan, Salina, Domchek, Susan M., Nathanson, Katherine L., Rebbeck, Timothy R., Phelan, Catherine, Narod, Steven, John, Esther M., Hopper, John L., Buys, Saundra S., Daly, Mary B., Southey, Melissa C., Terry, Mary-Beth, Tung, Nadine, Hansen, Thomas V. O., Osorio, Ana ORCID: 0000-0001-8124-3984, Benitez, Javier, Duran, Mercedes, Weitzel, Jeffrey N., Garber, Judy, Hamann, Ute, Peock, Susan, Cook, Margaret, Oliver, Clare T., Frost, Debra, Platte, Radka, Evans, D. Gareth, Eeles, Ros, Izatt, Louise, Paterson, Joan, Brewer, Carole, Hodgson, Shirley, Morrison, Patrick J., Porteous, Mary, Walker, Lisa, Rogers, Mark T., Side, Lucy E., Godwin, Andrew K., Schmutzler, Rita K., Wappenschmidt, Barbara, Laitman, Yael, Meindl, Alfons, Deissler, Helmut, Varon-Mateeva, Raymonda, Preisler-Adams, Sabine, Kast, Karin, Venat-Bouvet, Laurence, Stoppa-Lyonnet, Dominique, Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Easton, Douglas F., Klein, Robert J., Daly, Mark J., Friedman, Eitan, Dean, Michael, Clark, Andrew G., Altshuler, David M., Antoniou, Antonis C., Couch, Fergus J., Offit, Kenneth and Gold, Bert (2011). Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers. Hum. Genet., 130 (5). S. 685 - 700. NEW YORK: SPRINGER. ISSN 1432-1203

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Im, Kate M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirchhoff, TomasUNSPECIFIEDorcid.org/0000-0002-9055-2364UNSPECIFIED
Wang, XianshuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Green, ToddUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chow, Clement Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vijai, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korn, JoshuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaudet, Mia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fredericksen, ZacharyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pankratz, V. ShaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guiducci, CandaceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Crenshaw, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGuffog, LesleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kartsonaki, ChristianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morrison, JonathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Healey, SueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sinilnikova, Olga M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mai, Phuong L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greene, Mark H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piedmonte, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubinstein, Wendy S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hogervorst, Frans B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rookus, Matti A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collee, J. MargrietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoogerbrugge, NicolineUNSPECIFIEDorcid.org/0000-0003-2393-8141UNSPECIFIED
van Asperen, Christi J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meijers-Heijboer, Hanne E. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Roozendaal, Cees E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caldes, TrinidadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez-Segura, PedroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakubowska, AnnaUNSPECIFIEDorcid.org/0000-0002-5650-0501UNSPECIFIED
Lubinski, JanUNSPECIFIEDorcid.org/0000-0003-2931-3003UNSPECIFIED
Huzarski, TomaszUNSPECIFIEDorcid.org/0000-0003-3857-4854UNSPECIFIED
Blecharz, PawelUNSPECIFIEDorcid.org/0000-0001-5310-0054UNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDorcid.org/0000-0002-0916-2976UNSPECIFIED
Aittomaki, KristiinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lazaro, ConxiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanco, IgnacioUNSPECIFIEDorcid.org/0000-0002-7414-7481UNSPECIFIED
Barkardottir, Rosa B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montagna, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
D'Andrea, EmmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devilee, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olopade, Olufunmilayo I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhausen, Susan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peissel, BernardUNSPECIFIEDorcid.org/0000-0001-9233-3571UNSPECIFIED
Bonanni, BernardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peterlongo, PaoloUNSPECIFIEDorcid.org/0000-0001-6951-6855UNSPECIFIED
Singer, Christian F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rennert, GadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lejbkowicz, FlavioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glendon, GordUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ozcelik, HilmiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toland, Amanda EwartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caligo, Maria AdelaideUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beattie, Mary S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chan, SalinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domchek, Susan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nathanson, Katherine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rebbeck, Timothy R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phelan, CatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Narod, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
John, Esther M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hopper, John L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buys, Saundra S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, Mary B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Southey, Melissa C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Terry, Mary-BethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tung, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, Thomas V. O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osorio, AnaUNSPECIFIEDorcid.org/0000-0001-8124-3984UNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duran, MercedesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weitzel, Jeffrey N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garber, JudyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamann, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peock, SusanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cook, MargaretUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliver, Clare T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frost, DebraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Platte, RadkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, D. GarethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eeles, RosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izatt, LouiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paterson, JoanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brewer, CaroleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hodgson, ShirleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morrison, Patrick J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Porteous, MaryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walker, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rogers, Mark T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Side, Lucy E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Godwin, Andrew K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wappenschmidt, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laitman, YaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meindl, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deissler, HelmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Varon-Mateeva, RaymondaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preisler-Adams, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kast, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Venat-Bouvet, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoppa-Lyonnet, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, Robert J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, Mark J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedman, EitanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dean, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clark, Andrew G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altshuler, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antoniou, Antonis C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Offit, KennethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gold, BertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-486623
DOI: 10.1007/s00439-011-1003-z
Journal or Publication Title: Hum. Genet.
Volume: 130
Number: 5
Page Range: S. 685 - 700
Date: 2011
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-1203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TAY-SACHS DISEASE; BREAST-CANCER; POSITIVE SELECTION; GENOME; FREQUENCY; SIGNATURES; HISTORY; RISK; JEWSMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48662

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