Bio Agents

Title of Research: Heterozygote Advantage in Cystic Fibrosis

 

Hypothesis: The prevalence of cystic fibrosis among people of European ancestry is the result of heterozygote advantage.

 

Research proposal:

Cystic Fibrosis was a lethal genetic disease until a few decades ago. Despite the lethality of cystic fibrosis, it is prevalent among people of European ancestry. One of the possible causes for the prevalence of a genetic disease among a group of people is heterozygote advantage, in which an individual who has 1 disease gene and 1 normal gene, called a heterozygote, actually survives better than someone with 2 copies of the normal gene. Heterozygote advantage has been well documented in some people in Africa, in which the heterozygotes survive malaria better than people with 2 normal genes. We hypothesized that heterozygote advantage caused the prevalence of cystic fibrosis in Europe. The question is, Which infectious disease did the heterozygotes survive better than people with 2 normal genes in Europe? This infectious disease must be one that has afflicted Europe for a long time, and the cystic fibrosis heterozygotes, or carriers, survived it better than people with 2 normal genes.

 

4 infectious diseases have been proposed so far to explain the prevalence of cystic fibrosis: cholera, typhoid fever, traveler’s diarrhea, and tuberculosis. Among the 4, tuberculosis is the most likely candidate, because it has been prevalent in Europe for hundreds of years. Mycobacterium tuberculosis, the bacterium for tuberculosis, incorporates sulfate into its cell walls. CF carriers, however, have a reduced activity of arylsulfatase B activity, which is used by the bacteria to incorporate sulfate. The inability of M. tuberculosis to utilize sulfate in the synthesis of its cell walls reduces its virulence and provides protection to the CF carrier. 

 

In the following questionnaire, the questions are arranged in 3 clusters and are designed to accomplish these 3 goals: 1) Show that cystic fibrosis carriers are unique from people with 2 normal genes, however subtle the differences; 2) Show that cystic fibrosis carriers are less likely to suffer from certain infectious diseases or medical conditions; 3) Show that cystic fibrosis carriers have reduced arylsulfatase B activity through subjective symptoms.

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Reference:

Cystic Fibrosis: Understanding the Causes and Effects of Cystic Fibrosis and the Alternative Treatment Measures and Management, by Jordan Baines