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Genetic epidemiology of cystic fibrosis in Saguenay-Lac-St. Jean (Quebec, Canada)

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. Introduction. Descriptive case-control genetic epidemiological study

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Genetic epidemiology of cystic fibrosis in Saguenay-Lac-St. Jean (Quebec, Canada)

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  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 DF508 • 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

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

  6. SLSJ Epidemiological Map

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. References • 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. • 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. • DeBraekeleer M, Daigneault J. Spatial distribution of the DF508 mutation in cystic fibrosis. Human Biology. 1992;64:167-174. • 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.

  14. Cause Celebrè

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