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Biology 103
2002 First Paper
On Serendip
Cystic Fibrosis is the
most common, lethal disease among Caucasian people. In the
Cystic Fibrosis is an
autosomal recessive disease. For one to
have Cystic Fibrosis both of his or her parents must have the mutant gene
(ignoring the minute chance of spontaneous mutation). He or she has inherited two mutant genes, one
from each parent (he or she has no normal CFTR genes. When two carriers have a baby there is a 25%
chance their baby will not carry a mutant CFTR gene (homozygote dominant), a
25% chance their baby will have cystic fibrosis, carrying two mutant CFTR genes
(homozygote recessive), and a 50% chance
their baby will be a carrier of a mutant CFTR gene (heterozygote), as
illustrated in the diagram below.
|
MOTHER normal
(N) mutant (n) |
|
F A N T H E R n |
non-carrier NN |
carrier Nn |
carrier Nn |
Cystic
Fibrosis nn |
Cystic Fibrosis
affects the respiratory and digestive systems.
The CFTR protein normally forms channels in cell membranes, though these
channels flow chloride ions. In the
lungs this washes away bacteria, mucus and other debris. In the intestines it washes away pathogens and
brings digestive enzymes in contact with food.
In sweat glands these channels recycle salt out of the glands and back
into the skin before it is lost to the outside world2. In a person with Cystic Fibrosis thick mucus
blocks these channels. Their body cannot
perform these functions. This leads to
mucus buildup in the lungs, a prime breeding ground for bacteria. In the small intestine the enzymes that break
down fat cannot get to the food and digestive problems arise. On a hot day a person with Cystic Fibrosis is
at risk to dehydration10.
For years scientists
have been studying the possible benefits of the mutant CFTR gene. In 1967 A.G. Knudsen, L. Wayne, and W.Y. Hallett published an article in the American Journal of
Human Genetics. They collected data of
the numbers of live offspring of the Grandparents of CF children. They found that the mean number of offspring
for grandparents of CF children was higher (4.34) than the grandparents of a
control group (3.43) with only 0.30 standard error, concluding that CF
heterozygotes was associated with successful childbirth, and selectively
beneficial.
In more recent years
scientist identified the advantages of mutant CFTR carriers surviving
cholera. The lethal strain of Cholera, Vibrio cholerae,
produces a toxin that binds to the cells of the small intestine opening all of
the transmembrance regulating ducts pumping out considerable amounts of
chloride ions and water — about five gallons a day1. If the salt and water are not quickly
replaced the infected person dies of dehydration. Sherif Gabriel, a
cell physiologist of UNC Chapel Hill, experimented with mice that carried the
CF mutation and cholera. Not
surprisingly, the intestines of mice with cystic fibrosis infected with cholera
secreted no fluid. They lacked chloride
channels. The amazing discovery he found
was that mice that carried one mutant CFTR gene secreted only half the liquid
than the non-carrying mice. Gabriel
concluded that when cholera infected humans that carried a mutant CFTR, half as
much fluid secretion may have been enough to flush the intestines of the toxin
without succumbing to diarrhea, dehydration and death2. This
selective advantage to the many European outbreaks of cholera may explain the high
frequency of the gene mutation in Caucasian people of European decent. This argument, however, has been challenged
recently on the basis of time.
Not enough time has
past since Cholera reached
The reason the
frequency of CFTR heterozygotes4 in the
Caucasian Populations is so much higher at 1 in 25 than those of Hispanics
(1/46), Blacks (1/60), and Asians (1/150) has to do with a comparative
disadvantage that out ways advantages in the indigenous areas of these people. Physiologist Paul Quinton of the
It seems that one way
or another, dehydration is the variant in the frequency of cystic
fibrosis. In the cooler climate of
Northern Europe the mutant CFTR gene protected people from many fatal diseases
that cause diarrhea and dehydration (cholera, typhoid, E. coli), but in the
warm climates of the Americas, Southern
Europe, Africa and Asia this advantage was out weighed by the threat of heat
related dehydration. It is interesting
to see the advantages of diversity even in something as small as a gene.
Internet Sources
1How Cholera Became a
Killer, the one deadly strain of Vibrio
Cholerae
2Hidden Benefits,
the 52,000 year survival of the mutant gene that causes CF
3Cystic Fibrosis and
Typhoid Fever, rejection of the cholera hypothesis
4US Population
Frequency, statistics of the frequency of CF affected and carriers
5Selective Advantage
of CF Heterozygotes, 1960's study of live births among CF carriers
6Canadian Cystic
Fibrosis Foundation, tons of basic facts with search option
7WebMD—Cystic Fibrosis,
symptoms, cause, treatment, references
8Cystic
Fibrosis Research Directions, more sophisticated fact sheet
9United
Kingdom Cystic Fibrosis
10Scientific American CF
article, genetic defects underlying the disease