Human Genetics

, Volume 117, Issue 2–3, pp 119–132 | Cite as

Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families

  • Hélène Vézina
  • Francine DurocherEmail author
  • Martine Dumont
  • Louis Houde
  • Csilla Szabo
  • Martine Tranchant
  • Jocelyne Chiquette
  • Marie Plante
  • Rachel Laframboise
  • Jean Lépine
  • BCLC Haplotype Group
  • Heli Nevanlinna
  • Dominique Stoppa-Lyonnet
  • David Goldgar
  • Peter Bridge
  • Jacques Simard
Original Investigation


The Quebec population contains about six-million French Canadians, descended from the French settlers who colonized “Nouvelle-France” between 1608 and 1765. Although the relative genetic contribution of each of these founders is highly variable, altogether they account for the major part of the contemporary French-Canadian gene pool. This study was designed to analyze the role of this founder effect in the introduction and diffusion of the BRCA1 recurrent R1443X mutant allele. A highly conserved haplotype, observed in 18 French-Canadian families and generated using 17 microsatellite markers surrounding the BRCA1 locus, supports the fact that the R1443X mutation is a founder mutation in the Quebec population. We also performed haplotyping analysis of R1443X carriers on 19 other families from seven different nationalities; although the same alleles are shared for three markers surrounding the BRCA1 gene, distinct haplotypes were obtained in four families, suggesting multiple origins for the R1443X mutation. Ascending genealogies of the 18 French Canadian families and of controls were reconstructed on an average depth of 10 generations. We identified the founder couple with the highest probability of having introduced the mutation in the population. Based on the descending genealogy of this couple, we detected the presence of geographical concentration in the diffusion pattern of the mutation. This study demonstrates how molecular genetics and demogenetic analyses can complement each other to provide findings that could have an impact on public health. Moreover, this approach is certainly not unique to breast cancer genetics and could be used to understand other complex traits.


Founder Mutation Founder Population Ancestral Group Obligate Carrier R1443X Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors are indebted to the participants and their families for providing DNA samples. We would also like to thank Claire Brousseau, Sylvie Délos, Marie-Andrée Lajoie, Pascale Léger, Josée Rhéaume, Gilles Leblanc, Carolle Samson, Hélène Malouin, Nathalie Bolduc, Andrée McMillan and Tina Babineau of the Cancer Genomics Laboratory (Québec) and Jillian Parboosingh and Ross Mc Leod from the Molecular Diagnostic Laboratory (Alberta) for sample management and skillful technical assistance, Michèle Jomphe and France Néron from the BALSAC Project (Chicoutimi) as well as Lise Gobeil from the Interdisciplinary Research Group on Demography and Genetic Epidemiology (Chicoutimi) for genealogical reconstruction and analyses and Laurent Richard and Nicolas Lanouette from the Historical Geography Laboratory at Laval University for cartography work. We also appreciated advice received from the different ethics committees. This work was supported by the Fonds de la Recherche en Santé du Québec (FRSQ)/ Réseau de Médecine Génétique Appliquée (RMGA), the Canadian Breast Cancer Research Alliance and the Canadian Institutes of Health Research (CIHR) for the INHERIT BRCAs research program. F.D. is a recipient of a Research Career Award in the Health Sciences by IRSC/Rx&D HRF, J.S. is Chairholder of the Canada Research Chair in Oncogenetics.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Hélène Vézina
    • 1
  • Francine Durocher
    • 2
    Email author
  • Martine Dumont
    • 2
  • Louis Houde
    • 1
  • Csilla Szabo
    • 3
  • Martine Tranchant
    • 2
  • Jocelyne Chiquette
    • 4
  • Marie Plante
    • 5
  • Rachel Laframboise
    • 6
  • Jean Lépine
    • 7
  • BCLC Haplotype Group
  • Heli Nevanlinna
    • 8
  • Dominique Stoppa-Lyonnet
    • 9
  • David Goldgar
    • 3
  • Peter Bridge
    • 10
  • Jacques Simard
    • 2
    • 11
  1. 1.Interdisciplinary Research Group on Demography and Genetic Epidemiology (GRIG)University of Quebec at ChicoutimiChicoutimiCanada
  2. 2.Cancer Genomics LaboratoryCHUL Research Center, CHUQ, Laval UniversitySainte-FoyCanada
  3. 3.Genetic Epidemiology UnitInternational Agency for Research on CancerLyon, Cedex 08France
  4. 4.Clinique des maladies du sein Deschênes-FabiaHôpital du Saint-SacrementCanada
  5. 5.Service de gynécologieCHUQ, L’Hôtel-Dieu de QuébecCanada
  6. 6.Service de médecine génétiqueCHUQCanada
  7. 7.Center hospitalier régional de RimouskiRimouskiCanada
  8. 8.Department of Obstetrics and GynecologyHelsinki University Central HospitalHelsinkiFinland
  9. 9.Department of GeneticsInstitut CurieParis, Cedex 05France
  10. 10.Molecular Diagnostic LaboratoryAlberta Children’s HospitalCalgaryCanada
  11. 11.Canada Research Chair in Oncogenetics, Faculty of Medicine Laval UniversityCanada

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