At the keyword site CFTR you can learn about geographical variation in common cystic fibrosis mutations in the human population. The high frequency of the disease has been difficult to explain in view of the seriousness of the condition in affected individuals. Supposing that mutant alleles are completely recessive, and that the frequency of homozygous recessives (1/1700) represents an equilibrium between mutation and selection, then the rate of mutation to new alleles would have to be 6 ¥ 10–4 per generation, which is much higher than can easily be explained. Another alternative is that heterozygotes have a selective advantage of some kind, so the mechanism of selection is actually overdominance. Recent data support the hypothesis that heterozygotes are more resistant to typhoid fever. The bacterium Salmonella typhi, the pathogen for typhoid fever, invades the gastrointestinal system through the CFTR membrane channel encoded in the CFTR gene. Cells expressing wildtype CFTR internalize more S. typhi than mutant cells, and transgenic mice that are heterozygous for CFTR mutations internalize 86 percent fewer bacteria than do wildtype homozygotes. The resistance hypothesis is also consistent with the high frequency of particular CFTR mutations that are found in patients.

The occasionally extreme effects of random genetic drift are dramatically illustrated by Pingelap disease, a form of total color blindness combined with extreme nearsightedness and cataract, which affects 4–10 percent of the Pingelapese people of the eastern Caroline Islands in the Pacific, who are blind from infancy. Consult this keyword site to learn the molecular and cellular basis of this condition, and why its frequency is so high in this particular human population.

Back to Keyword Hot Links for all chapters

Back to eLearning for all chapters