In cell biology, males and females differ: men have X chromosomes, so women have two. How can we cause the difference? Geneticists at the University of Geneva (UNIGE), in Switzerland, a 1960s historical research, suddenly sealed the skin and blood cells. Second X chromosomes have been gradually deactivating in women to prevent overloaded X-encoded genes. Several genes also passed this deactivation, which changed according to the tissue and the cell of life. The UNIGE study explains the differences between men and women with genetic diseases. You can read everything about the journal's results PNAS.
DNA is made up of genes that represent the RNA until they become proteins. RNA is therefore the product of proteins in our cells. "Our laboratory has designed a pioneering technique that calls single-cell allele as a sequence of specific RNAs, which means RNA molecules can be sequenced from the cellular cell for the first time and not in their entirety," explains Christelle Borel, Department Researcher in Genesis and Development UNIGE's Faculty of Medicine. This exact analysis can be used according to what happens in each cell, and the gene continues through the gene.
Stylianos Antonarakis, Emeritus Professor at the Faculty of Medicine, explores the possibility of deactivating two women X chromosomes, discovered by Mary F. Lyon in 1960. British researchers show that there are two X chromosomes, unlike men, and one of them is silent through a mechanism of gene correction, compensating for the presence of women with an extra copy of the X chromosome. In the 1990s, however, some scientists were deactivating the X chromosome by preventing this deactivation. But how?
Gradual cellular deactivation
The UNIGE researchers included 935 skin cells and 48 blood samples from 48 different females to analyze the phenomenon. "We analyzed cells individually and examined the genes expressed in each cell," says Federico Santoni, former researcher at the Department of Genetics and Development at the Faculty of Medicine of the UNIGE and currently a researcher at CHUV in Lausanne. "Then we sequenced five women and the bioinformatic genome, the X chromosome of each cell was activated and it was silent."
Until recently, experimental techniques were not measured by the expression rates of genes that escaped sensitivity. Nowadays, however, thanks to an experimental and bioinformatic approach developed by UNIGE, the geneticist has identified 55 of these genes, including five yet unknown ones. "Our main finding is that the X chromosomes that were not studied in cells are not 100% inactive, the rate varies from one cell to the other," says Antonarakis. X chromosome deactivation begins with the expression of the XIST gene. "This gene produces small RNA molecules that surround the X-R chromosomes, which means that the genes are silent in this chromosome. We have shown that the XIST RNA molecules further deactivate this chromosome, silent genes and vice versa, which explains a variable cell deactivation between cells."
XIST is the key gene to deactivate two X chromosomes in female cells. But it's not the only one. "For the first time we found five genes that play a key role in the X chromosome deactivation mechanism," says Borel. "This will help us with what happens when the level of the molecule is turned off. More importantly, we can increase our research to discover the differences between men and women in diseases."
X deactivation: a new understanding of genetic diseases?
There are many illnesses caused by genes X chromosome, such as hemophilia, intellectual disability syndromes and developmental disorders. "During our research, we have seen that the X chromosome deactivation also changed the different stages of life of a cell and the cell type," says Professor Antonarakis. "This may have differences in occurrence in the severity of some illnesses of patients and the age of occurrence and why the tissues are directed by certain diseases." According to these results, the researchers can highlight the mechanisms behind heterogeneity. genetic diseases
University of Genève. .