Cystic Fibrosis

Question

Why is cystic fibrosis more common in light-skinned than in dark-skinned people?

Answer

Hello,

The incidence of a monogenic disease depends on the mutation rate of the affected gene on the one hand and the selection of the mutated allele on the other.

The most common CFTR mutation worldwide, F508del, is estimated to have originated more than 40.000 years ago in Northwestern Europe and was later spread across Europe and further to the other continents during the Migration Period (Mateu E et al. 2002). The fact that this mutation is so common means that it has never been sorted out since its occurrence and could be passed down through generations. One hypothesis that might explain this phenomenon is that during the times of the cholera and typhus epidemics, heterozygous carriers of a CF mutation had an advantage compared to people with two intact CFTR genes because, thanks to the more viscous secretions, they dehydrated less quickly and therefore survived more easily.

In conclusion, one can say that cystic fibrosis is more common in the light-skinned population because its geographic source lies in a region from which the light-skinned population originates and because, due to a so-called heterozygous advantage, the oldest CF mutation could spread very widely within this population group before eventually being distributed across the world as a result of migration.

I hope this answers your question – kind regards,
Prof. Sabina Gallati

22.10.2013