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

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
(No Transcript)
6
(No Transcript)
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

• Daigneault J, Aubin G, Simard F, DeBraekeleer M.
  Genetic epidemiology of cystic fibrosis in
  Saguenay-Lac-St. Jean (Quebec, Canada). Clinical
  Genetics. 199140298-303.
• 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. 199242360-364.
• DeBraekeleer M, Daigneault J. Spatial
  distribution of the DF508 mutation in cystic
  fibrosis. Human Biology. 199264167-174.
• Daigneault J, Aubin G, Simard F, DeBraekeleer M.
  Incidence of cystic fibrosis in Saguenay-Lac-St.
  Jean (Quebec, Canada). Human Biology.
  199264115-119.

16
Cause Celebrè