1. Genetic epidemiology of cystic fibrosis in Saguenay-Lac-St. Jean (Quebec, Canada) Daigneault J, Aubin G, Simard F, DeBraekeleer M Clinical Genetics April 1991 Presented by Soodtida Tangpraphaphorn

2. Introduction Descriptive case-control genetic epidemiological study –Quantifies incidence, prevalence, carrier rates –Some E  O associations, no causality established Makes etiological hypotheses, suggests associations and causal relationships for future study Study population shows elevated prevalence of CF compared to overall population at risk. Inbreeding slightly higher in CF group compared to controls due to remote consanguinity. Endogamy not higher in CF group than controls.

3. Clinical Cystic Fibrosis Genetic respiratory illness with pleiotropy –Most commonly affects populations of NW European descent –Causes airway mucus to thicken, resulting in chronic respiratory obstruction and infections –Impairs pancreatic exocrine function –Complications can decrease lifespan –Diagnosed by sweat test

4. Cellular Cystic Fibrosis Caused by mutation in CFTR gene –Most commonly  F508 Mutation results in defective protein product –Protein is a cell membrane ion channel Defective protein affects chloride anion transport in/out of cell –Ion channel fails to export to cell membrane –Ion channel is in cell membrane, but cannot function

7. Saguenay-Lac-St.Jean 200km NE of Quebec City Inlet of St. Lawrence Seaway Very geographically remote Southernmost fjord in the world

8. SLSJ Epidemiological Map

9. Study Population Pop. 285,100 (1986); 98% French-speaking Catholics Isolation –Settled in 1840s, migrated from Charlevoix –Founder effects Mutation frequencies different from urban Canadian population Particularly interesting to geneticists –Elevated carrier rates and prevalence of many different genetic disorders

10. Study Population 127 CF cases in SLSJ –125 patients from CF clinic at Chicoutimi, 2 from Quebec City 3 groups population-based controls –Not described in this study Requires readers to refer to investigators’ other studies

11. Methods Study time-frame (1975-1988) Extract demographic information from database of CF cases in SLSJ Migration histories from subjects and their families Calculate prevalence & incidence from birth statistics and case data Estimate carrier rate via Hardy-Weinberg equation

12. Results Number of CF live births = 78 Total live births = 70351 CF incidence (#cases/#at risk) = 1 per 902 –Incidence for all Canadian whites = 1 per 2500 –Secular trends show stable annual IR Hardy-Weinberg carrier rate = 1 per 15 Stronger kinship and more inbreeding in CF group

13. Discussion SLSJ population not isolated for long periods of time –High prevalence may be attributable to mutations before migration from Charlevoix –Migration of large founder group brought many alleles into population Different frequency of mutations Good descriptive epidemiology –Study stands alone well, better when taken in context

14. Prevention Recommendations Primary – increase genetic diversity by mating outside of population Secondary – screen locals for genetic mutations and offer genetic counseling with family planning, incl. PGD Tertiary – early detection in infants, more social-medical services, close medical supervision

15. References 1.Daigneault J, Aubin G, Simard F, DeBraekeleer M. Genetic epidemiology of cystic fibrosis in Saguenay-Lac- St. Jean (Quebec, Canada). Clinical Genetics. 1991;40:298-303. 2.Rozen R, DeBraekeleer M, Daigneault J, Ferreira-Rajabi L, Gerdes M, Lamoureaux L, Aubin G, Simard F, Fujiwara TM, Morgan K. Cystic fibrosis mutations in French Canadians: three CFTR mutations are relatively frequent in a Quebec population with an elevated incidence of cystic fibrosis. American Journal of Medical Genetics. 1992;42:360-364. 3.DeBraekeleer M, Daigneault J. Spatial distribution of the DF508 mutation in cystic fibrosis. Human Biology. 1992;64:167-174. 4.Daigneault J, Aubin G, Simard F, DeBraekeleer M. Incidence of cystic fibrosis in Saguenay-Lac-St. Jean (Quebec, Canada). Human Biology. 1992;64:115-119.

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