The human domain explains the origin of some hereditary diseases

2025/01/14 Galarraga Aiestaran, Ana - Elhuyar Zientzia Iturria: Elhuyar aldizkaria

• Osasuna
• Genetika
• Biokimika

Protein domains are specific areas. They have special folds, allowing them to create stable structures, with their own function, different from the rest of the protein. Researchers have made a total of five hundred domains of human proteins, and substituting each one's amino acids for all the amino acids, they've created a collection of 1 human dominoma. This domain is, therefore, a catalog of mutations that can occur, and that is where researchers have found the causes of some hereditary diseases.

Although human domeninoma 1 represents only 2.5% of known human proteins, it is the largest catalog of this type to date. To see the consequences of mutations, researchers have introduced the mutated domains into yeast cells. Thus, they have identified the failures and instability they produce, and some of them have come to the conclusion that they are at the root of specific diseases.

The results have been published in Nature. Examples include beta-gamma crystalline proteins. They are essential to maintain the transparency of the lens of the human eye and researchers observed that 71% of cataract or cataract related mutations lead to destabilization of these proteins. This facilitates the accumulation and creation of opaque fields in the lens.

Other mutations do not destabilize the protein, but they affect functions at the molecular level. This is the case, for example, of Rett's syndrome. This syndrome causes significant physical and cognitive impairment and originates from mutations in the MECP2 gene. The study found that many MECP2 mutations do not destabilize the protein, but influence how it is associated with DNA, which causes disability.

Researchers have recognized that the research is limited, since they have worked with yeast cells, and other factors may influence organisms. However, the knowledge of the functioning of the domains studied on such a meticulous scale allows the development of better treatments for certain diseases.