It is research by the CRG, Center for Genomic Regulation of Barcelona, which should allow finding personalized treatments for these diseases.
Diseases such as hereditary cataracts or Rett syndrome are caused by a specific and known genetic mutation. But how it does this was unknown. Research from the Center for Genomic Regulation (CRG) has set out to answer this ambitious question: what is the majority mechanism that triggers a hereditary genetic disease .
They have studied this in yeast cells. They have been used to test how more than 500 human proteins behave , in which half a million mutations have been introduced.
A large-scale study published in the journal Nature has revealed that the main mechanism behind these diseases is protein instability .
Protein instability
In three out of five cases, the mutation of a gene causes the protein it encodes to not fold correctly. "A protein, after all," explains Antoni Beltran Marquès, a postdoctoral researcher at the CRG, "is nothing more than a very long chain of amino acids, which inside the cell must fold and reach its final shape, and when proteins are not folded properly, they cannot carry out their function and are sometimes also degraded by the cell."
Then, they can give rise to hereditary genetic diseases. If we take the two examples from the beginning, in the case of hereditary cataracts, the faulty folding of proteins is the mechanism that explains them. The unstable proteins group together and form opaque areas in the lens .
However, this mechanism is not the majority in Rett syndrome, a very serious and disabling neurological disorder. Many times, here, the mutation causes the protein not to adhere well to the DNA and has a loss of function that could be altering the development and functioning of the brain.
Previous step to find personalized treatments
Knowing exactly what causes a genetic disease - whether it's because a protein folds incorrectly or through some other mechanism - is vital when designing personalized drugs. And this is important, because the vast majority of these diseases currently have no curative treatment .
This CRG research is only a first step towards achieving this, but it is essential. And it is relevant, because most of these genetic diseases are minority , affecting only a few people. Until now, they have been studied one by one, individually, and with little interest from the pharmaceutical industry, which sees little economic return.
On the other hand, "with this type of large-scale study, we can study many different mutations, in many different diseases, in the same experiment," says researcher Antoni Beltran Marquès.
Large database available to science
The result of this research is the largest catalog of genetic mutations and their effect on proteins ever generated . A large database that is now available to the international scientific community for future research.
Despite being the most comprehensive, it only covers 2.5% of human proteins. The work that remains to be done, therefore, is enormous. But patterns have been described that allow us to predict how some proteins that have not yet been described will behave .
This is because proteins can be classified into families, with similar structures. "What we have seen," says Beltran Marquès, "is that by measuring mutations in a small number of the same family, it is possible to predict quite correctly the effects of mutations in other proteins in the same family."
.jpg)
0 Comments