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Article Dans Une Revue Human Genetics Année : 2011

Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.

Kate M Im (1) , Tomas Kirchhoff (2) , Xianshu Wang (3) , Todd Green (4) , Clement y Chow (5) , Joseph Vijai , Joshua Korn , Mia M Gaudet , Zachary Fredericksen (6) , V. Shane Pankratz , Candace Guiducci , Andrew Crenshaw , Lesley Mcguffog (7) , Christiana Kartsonaki (7) , Jonathan Morrison , Sue Healey (8) , Olga M Sinilnikova (9, 10) , Phuong L Mai , Mark H Greene (11) , Marion Piedmonte (12) , Wendy S Rubinstein , Frans B Hogervorst , Matti A Rookus , J Margriet Collée (13) , Nicoline Hoogerbrugge (14) , Christi J van Asperen , Hanne E J Meijers-Heijboer , Cees E van Roozendaal , Trinidad Caldes (15) , Pedro Perez-Segura , Anna Jakubowska (16) , Jan Lubinski (16) , Tomasz Huzarski (17) , Paweł Blecharz , Heli Nevanlinna (18) , Kristiina Aittomäki (19) , Conxi Lazaro (20) , Ignacio Blanco (21) , Rosa B Barkardottir , Marco Montagna (22) , Emma d'Andrea (23) , Peter Devilee (24) , Olufunmilayo I Olopade , Susan L Neuhausen , Bernard Peissel (25) , Bernardo Bonanni (26) , Paolo Peterlongo (27) , Christian F Singer , Gad Rennert (28) , Flavio Lejbkowicz (28) , Irene L Andrulis , Gord Glendon (29) , Hilmi Ozcelik (30, 31) , Amanda Ewart Toland , Maria Adelaide Caligo (32) , Mary S Beattie , Salina Chan , Susan M Domchek , Katherine L Nathanson (33) , Timothy R Rebbeck , Catherine Phelan , Steven Narod (34) , 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 (35, 36) , Javier Benitez (35, 36) , Mercedes Durán (37) , Jeffrey N Weitzel , Judy Garber , Ute Hamann (38) , Non Renseigné , Susan Peock (7) , Margaret Cook (7) , Clare T Oliver , Debra Frost (7) , Radka Platte (7) , D Gareth Evans (39) , Ros Eeles (40) , Louise Izatt (41) , Joan Paterson (42) , Carole Brewer (43) , Shirley Hodgson (44) , Patrick J Morrison , Mary Porteous (45) , Lisa Walker (46) , Mark T Rogers , Lucy E Side , Andrew K Godwin , Rita K Schmutzler , Barbara Wappenschmidt (47) , Yael Laitman (48) , Alfons Meindl (49) , Helmut Deissler (50) , Raymonda Varon-Mateeva (51) , Sabine Preisler-Adams (52) , Karin Kast (53) , Laurence Venat-Bouvet (54) , Dominique Stoppa-Lyonnet (55, 56) , Georgia Chenevix-Trench (8) , Douglas F Easton (57, 58) , Robert J Klein , Mark J Daly , Eitan Friedman (48, 59) , Michael Dean , Andrew G Clark (60) , David M Altshuler , Antonis C Antoniou , Fergus J Couch , Kenneth Offit (61) , Bert Gold
1 center for cancer research
2 Department of Environmental Medicine
3 Department of Laboratory Medicine and Pathology
4 Department of Genetics [Boston]
5 Cornell University [New York]
6 Department of Medical Genetics
7 Centre for Cancer Genetic Epidemiology
8 Queensland Institute of Medical Research
9 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
10 Centre Léon Bérard [Lyon]
11 Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics
12 Statistical and Data Center
13 Department of Clinical Genetics
14 Human Genetics
15 Molecular Oncology Laboratory
16 Department of Genetics and Pathology
17 Department of Genetics and Pathology
18 Department of Obstetrics and Gynecology
19 Department of Clinical Genetics
20 Molecular Diagnostic Unit
21 Genetic Counselling Unit
22 Immunology and Molecular Oncology Unit
23 Department of Oncology and Surgical Sciences
24 Department of Genetic Epidemiology
25 Unit of Medical Genetics
26 Division of Cancer Prevention and Genetics
27 Unit of Molecular Bases of Genetic Risk and Genetic Testing
28 Department of Community Medicine and Epidemiology
29 Ontario Cancer Genetics Network
30 Departments of Molecular Genetics and Laboratory Medicine and Pathobiology
31 Samuel Lunenfeld Research Institute
32 Section of Genetic Oncology
33 Depts of Medicine and Biostatistics and Epidemology
34 Women's College Research Institute
35 Human Genetics Group
36 Biomedical Research Centre Network for Rare Diseases
37 Institute of Biology and Molecular Genetics
38 Molecular Genetics of Breast Cancer
39 Genetic Medicine
40 Oncogenetics Team
41 Clinical Genetics
42 Department of Clinical Genetics
43 Department of Clinical Genetics
44 Medical Genetics Unit
45 South East of Scotland Regional Genetics Service
46 Oxford Regional Genetics Service
47 Department of Gynaecology and Obstetrics
48 The Susanne Levy Gertner Oncogenetics Unit
49 Department of Gynaecology and Obstetrics
50 Department of Gynaecology and Obstetrics
51 Institute of Human Genetics
52 Institute of Human Genetics
53 Department of Gynaecology and Obstetrics
54 Service d'Oncologie médicale [CHU Limoges]
55 Service de Génétique Oncologique
56 U830 - Unité de génétique et biologie des cancers
57 Cancer Research U.K. Genetic Epidemiology Unit
58 Genetic Epidemiology Unit, Department of Public Health and Primary Care
59 Sackler Faculty of Medicine
60 Departement of Molecular Biology and Genetics [CALS]
61 Clinical Genetics Service
Joseph Vijai
Joshua Korn
  • Fonction : Auteur
Mia M Gaudet
  • Fonction : Auteur
V. Shane Pankratz
  • Fonction : Auteur
Candace Guiducci
  • Fonction : Auteur
Andrew Crenshaw
  • Fonction : Auteur
Jonathan Morrison
  • Fonction : Auteur
Phuong L Mai
  • Fonction : Auteur
Wendy S Rubinstein
  • Fonction : Auteur
Frans B Hogervorst
  • Fonction : Auteur
Matti A Rookus
  • Fonction : Auteur
Christi J van Asperen
  • Fonction : Auteur
Hanne E J Meijers-Heijboer
  • Fonction : Auteur
Cees E van Roozendaal
  • Fonction : Auteur
Pedro Perez-Segura
  • Fonction : Auteur
Anna Jakubowska
Paweł Blecharz
  • Fonction : Auteur
Rosa B Barkardottir
  • Fonction : Auteur
Peter Devilee
Olufunmilayo I Olopade
  • Fonction : Auteur
Susan L Neuhausen
  • Fonction : Auteur
Christian F Singer
  • Fonction : Auteur
Irene L Andrulis
  • Fonction : Auteur
Amanda Ewart Toland
  • Fonction : Auteur
Mary S Beattie
  • Fonction : Auteur
Salina Chan
  • Fonction : Auteur
Susan M Domchek
  • Fonction : Auteur
Timothy R Rebbeck
  • Fonction : Auteur
Catherine Phelan
  • Fonction : Auteur
Esther M John
  • Fonction : Auteur
John L Hopper
  • Fonction : Auteur
Saundra S Buys
  • Fonction : Auteur
Mary B Daly
  • Fonction : Auteur
Melissa C Southey
  • Fonction : Auteur
Mary-Beth Terry
  • Fonction : Auteur
Nadine Tung
  • Fonction : Auteur
Thomas V O Hansen
  • Fonction : Auteur
Jeffrey N Weitzel
  • Fonction : Auteur
Judy Garber
  • Fonction : Auteur
Non Renseigné
  • Fonction : Auteur
Clare T Oliver
  • Fonction : Auteur
D Gareth Evans
  • Fonction : Auteur
Ros Eeles
  • Fonction : Auteur
Louise Izatt
  • Fonction : Auteur
Patrick J Morrison
  • Fonction : Auteur
Mark T Rogers
  • Fonction : Auteur
Lucy E Side
  • Fonction : Auteur
Andrew K Godwin
  • Fonction : Auteur
Rita K Schmutzler
  • Fonction : Auteur
Robert J Klein
  • Fonction : Auteur
Mark J Daly
  • Fonction : Auteur
Michael Dean
  • Fonction : Auteur
David M Altshuler
  • Fonction : Auteur
Antonis C Antoniou
  • Fonction : Auteur
Fergus J Couch
  • Fonction : Auteur
Bert Gold
  • Fonction : Auteur

Résumé

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.

Domaines

Cancer

Dates et versions

hal-00837832 , version 1 (24-06-2013)

Identifiants

Citer

Kate M Im, Tomas Kirchhoff, Xianshu Wang, Todd Green, Clement y Chow, et al.. Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.. Human Genetics, 2011, 130 (5), pp.685-99. ⟨10.1007/s00439-011-1003-z⟩. ⟨hal-00837832⟩
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