Human Genetics

, Volume 89, Issue 1, pp 83–87

The French Canadian Tay-Sachs disease deletion mutation: identification of probable founders

  • M. De Braekeleer
  • P. Hechtman
  • E. Andermann
  • F. Kaplan
Original Investigations

Summary

Tay-Sachs disease (TSD) is an inherited neurodegenerative ganglioside storage disorder caused by deficiency of the hexosaminidase A enzyme. A deletion allele (FCD) at the HEXA locus has attained high frequency in the French Canadian population. The distribution of affected probands shows a likely center of diffusion for this mutation located in the Bas-St.-Laurent and Gaspésie regions of the province of Quebec. We have reconstructed the genealogies of 15 obligate carriers of the FCD allele to an average depth of 12 generations identifying 60 ancestors and 80 European founders common to all of them. The ancestral origins of the European founders show a significantly greater number of individuals born in the French provinces of Normandy and Perche than expected based on information regarding the origins of the 8,500 immigrants who settled the colony of New France during the French regime. We have identified common ancestors among the 10 who were born in Quebec who appear to be likely candidates for the origin of the FCD mutation. One such couple had 11 children, 5 of whom settled in regions of Quebec or New Brunswick that today have elevated heterozygote frequencies for the FCD. The five offspring are ancestors of all known carriers. By contrast, the absence of FCD alleles among TSD probands in France suggests that the mutation did not occur in a European founder.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andermann E, Andermann F, Patry G, Lafontaine R, Geoffroy G, Scriver CR, Wolfe L (1973) Tay-Sachs disease in Quebec: evidence for a geographic aggregate in the French-Canadian population and identification of a new retardation syndrome with possible linkage to the Tay-Sachs gene. Trans Am Neurol Assoc 98:17–21Google Scholar
  2. Andermann E, Scriver CR, Wolfe LS, Dansky L, Andermann F (1977) Genetic variants of Tay-Sachs disease: Tay-Sachs disease and Sandhoff disease in French Canadians, and a Tay-Sachs screening program in the French-Canadian population. Prog Clin Biol Res 18:161–188Google Scholar
  3. Bouchard G, Ruy R, Casgrain B (1985) Reconstruction automatique des familles: le système SOREP. SOREP, ChicoutimiGoogle Scholar
  4. Charbonneau H, Robert H (1987) The French origin of the Canadian population 1608–1795. In: Harris RC, Matthews G (eds) Historical atlas of Canada, vol 1. University of Toronto Press, Toronto, pp 118–119Google Scholar
  5. Charbonneau H, Desjardins B, Guillemette A, Landry Y, Légaré J, Nault F (1987) Naissance d'une population: les Francais établis au Canada au XVIIe siècle. Presses Universitaires de France (INED), Paris; Presses de l'Université de Montréal, MontréalGoogle Scholar
  6. De Braekeleer M (1991) BELGE: un ensemble d'analyse génétique des généalogies. (Technical report III-C-64) SOREP, ChicoutimiGoogle Scholar
  7. De Braekeleer M, Larochelle J (1990) Genetic epidemiology of hereditary tyrosinemia in Saguenay-Lac-St. -Jean and in Quebec. Am J Hum Genet 47:302–307Google Scholar
  8. De Braekeleer M, Morgan K, Jomphe M, Bouchard G, Davignon J, Gradie M, Kessling A, Laberge C, Moorjani S, Roy M, Scriver CR (1988) Familial hypercholesterolemia in French-Canadians: geographical distribution and centre of origin of an LDL-receptor deletion mutation: (Technical report III-C-60) SOREP, ChicoutimiGoogle Scholar
  9. De Braekeleer M, John S, Leggett D, Laframboise R, Laberge C, Rozen R, Scriver CR (1990) A center of diffusion in 17th century France for the M1V allele in French Canadians. Am J Hum Genet 47:A131Google Scholar
  10. De Braekeleer M, Dionne C, Gagné C, Julien P, Brun D, Murthy MRV, Lupien PJ (1991) Founder effect in familial hyperchylomicronemia in French Canadians of Quebec. Hum Hered 41:168–173Google Scholar
  11. Hechtman P, Kaplan F, Bayleran J, Boulay B, Andermann E, De Braekeleer M, Melançon S, Lambert M, Potier M, Gagné R, Kolodny E, Clow C, Capua A, Prevost C, Scriver CR (1990) More than one mutant allele causes infantile Tay-Sachs disease in French-Canadians. Am J Hum Genet 47:814–822Google Scholar
  12. Jetté R (1983) Dictionnaire généalogique des familles du Québec. Presses de l'Université de Montréal, MontréalGoogle Scholar
  13. Jomphe M, Bouchard G, Davignon J, DeBraekeleer M, Gradie M, Kessling A, Laberge C, Moorjani S, Morgan K, Roy M, Scriver CR (1988) Familial hypercholesterolemia in French-Canadians: geographic distribution and center of origin of an LDL-receptor deletion mutation. Am J Hum Genet 43:A216Google Scholar
  14. Kaplan F, Boulay B, Bayleran J, Hechtman P (1991) Allele specific amplification of genomic DNA for detection of deletion mutations: identification of a French-Canadian Tay-Sachs mutation. J Inherited Metab Dis 14:707–714Google Scholar
  15. Myerowitz R, Hogikyan ND (1986) Different mutations in Ashkenazi Jewish and non-Jewish French-Canadians with Tay-Sachs disease. Science 232:1646–1648Google Scholar
  16. Myerowitz R, Hogikyan ND (1987) A deletion involving Alu sequences in the β-hexosaminidase α-chain gene of French-Canadians with Tay-Sachs disease. J Biol Chem 262:15396–15399Google Scholar
  17. Okada S, O'Brien JS (1969) Tay Sachs disease: generalized absence of a β-d-N-hexosaminidase component. Science 166:698–700Google Scholar
  18. Pontbriand B (1978) Mariages du comté de Portneuf (1679–1950). SilleryGoogle Scholar
  19. Roberge C (1976) Répertoire des mariages de la paroisse St-Sauveur de Québec (1867–1971) Société de Généalogie de Québec, QuébecGoogle Scholar
  20. Talbot EG (1948) Recueil de généalogies des comtés de Beauce-Dorchester-Frontenac 1625–1946. Collège du Sacré-Coeur, BeaucevilleGoogle Scholar
  21. Tanguay C (1871) Dictionnaire généalogique des familles canadiennes. Eusèbe-Sénécal, QuébecGoogle Scholar
  22. Vicero RD (1968) Immigration of French-Canadians to New England 1840–1900: a geographical analysis. PhD thesis, University of WisconsinGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • M. De Braekeleer
    • 1
  • P. Hechtman
    • 2
    • 3
    • 4
  • E. Andermann
    • 3
    • 5
  • F. Kaplan
    • 2
    • 3
  1. 1.Research Laboratory in Genetic Epidemiology, Départment des Sciences HumainesUniversité du Québec à ChicoutimiChicoutimiCanada
  2. 2.Department of Biochemical GeneticsMcGill University, Montreal Children's Hospital Research InstituteMontrealCanada
  3. 3.Centre for Human GeneticsMcGill UniversityMontrealCanada
  4. 4.Biology DepartmentMcGill UniversityMontrealCanada
  5. 5.Department of NeurogeneticsMontreal Neurological HospitalMontrealCanada

Personalised recommendations