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Scientists from the EPFL and the University of Geneva have discovered a genetic mechanism that defines the shape of our fingers in which, surprisingly, genes play only a secondary role.
The research published in Cell, online the 23rd of November, shows the mechanism is found in a DNA sequence that was thought, incorrectly, to play no role. This long string has seven enhancers which, when combined, modify the activity of the genes responsible for the formation of the fingers an important fundamental discovery for the field of genetics.
The discovery could help us understand anomalies that are transmitted from generation to generation such as welded fingers, or extra and/or abnormally short fingers (Kantaputra syndrome) even if the genes appear perfectly normal.
Turbos on the genome
"The discovery we have made is that the group of genes involved in finger growth is modulated by seven enhancers, not just one, and they combine through contact," says Thomas Montavon, lead author of the article and researcher at the EPFL.
When the fingers in the embryo begin to take shape, a string of DNA folds and enhancers located on different parts of that string come into contact. This contact stimulates various proteins to activate specific genes, and fingers start to grow.
If one of the seven enhancers is missing, the fingers will be shorter, or abnormally shaped. When two enhancers are missing, the defects are even more pronounced. Without enhancers, the genes work slowly, and generate only the beginnings of fingers.
How the DNA folds in exactly the right way so that the enhancers will work correctly remains largely unknown.
"In other tissues, such as the brain, the string of DNA folds differently," says Denis Duboule, director of the study and researcher at both the EPFL and the University of Geneva. "To our knowledge, it is only in the fingers that it adopts this shape."
An explanation for evolutionary diversity
"Just think of some ungulates, which walk on a single finger, or the ostrich, which has only two, and the human hand, of course" explains Denis Duboule.
Other genetic processes may also function on the basis of a similar principle. This could explain the diversity of the products of evolution, in areas other than the fingers, according to Denis Duboule.
"When a mutation occurs on a gene, for instance in cystic fibrosis, it is often binary. This amounts to an 'all or nothing' situation. With the mechanism we have discovered, it is a 'more or less' situation. If it is combined, it is modulated."
This research is carried out within the National Center of Competence in Research (NCCR) Frontiers in Genetics. The NCCRs are an initiative of the Swiss government to stimulate research and education in key areas. http://www.frontiers-in-genetics.org
Vidéo (interview with Denis Duboule) : http://www.youtube.com/watch?v=jrFG34HPqN8