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
– 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.
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
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
Saguenay-Lac-St.Jean
• 200km NE of
Quebec City
• Inlet of St. Lawrence
Seaway
• Very geographically
remote
• Southernmost fjord
in the world
SLSJ Epidemiological Map
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
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
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
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
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
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
References
1.
2.
3.
4.
Daigneault J, Aubin G, Simard F, DeBraekeleer M.
Genetic epidemiology of cystic fibrosis in Saguenay-LacSt. 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.
Cause Celebrè