History of Cystic Fibrosis

Question

Hello,
I would like to know if cystic fibrosis has always existed since the appearance of human beings on earth or, if not, about which century this disease appeared.
What evolutionary process has led to a genetic error on the CFTR gene?
Thank you very much.

Answer

Hello,

No, cystic fibrosis has not always existed: the mutations that cause it are natural, random mutations. It seems that the mutation F508del, the most frequent CFTR mutations, appeared in humans tens of thousands of years ago, without more precision.

A mutation is a rare, natural, accidental or induced modification of genetic information (DNA or RNA sequence) in the genome. Natural mutations are random, but their frequency of occurrence can be increased by mutagens, sometimes referred to as agents or mutagenic factors. These agents can be physical (ionizing radiation) or chemical (alkylating agents, reactive oxygen derivatives, etc.). Our cells have DNA repair systems to prevent the spread of these unwanted events, but sometimes point mutations escape this monitoring.

Depending on the part of the affected genome, the consequences of a mutation may vary. Somatic mutations do not affect cells intended for reproduction, so they are never hereditary. The germinal mutations, or de novo mutations, relate to the DNA of the stem cells of a gamete (ovum or spermatozoon). In this case, the embryo will carry the mutation while none of its parents possessed it in its genetic heritage. These germinal mutations are hereditary, transmitted to the next generation. The occurrence of de novo mutations is very rare but, as it is transmitted to succeeding generations, its frequency in the general population may become significant (as in cystic fibrosis: one in every 33 is carrying a mutation of the CFTR gene in The French population). Moreover, the greater probability of mutation due to the length of the CFTR gene explains the large number of CFTR mutations identified to date (about 2000).

Genetic mutations are one of the elements of biodiversity and one of the many factors in the evolution of species.

You will find more complete information on the Wikipedia site with the keyword "Genetic mutation".

Hope this answer can help.
Best wishes
Gilles RAULT, MD, Roscoff CF Center

14.02.2017