Thursday , July 7 2022

Study: How genetics become hyalitarian – (Details)


In cell biology, men and women are unequal: men have a chromosome X, while women have two. How can we get this difference? Genetics from the University of Geneva (UNIGE), Switzerland, turned to historical research dating from the 1960s to follow the skin and blood cells one by one. They observed how the second chromosome X in women becomes inactive gradually to avoid an overdose of genes encoded by the X. They also find that several generators avoid this inactivity, and which varied according to tissue and cell life periods. The UNIGE research explains the inequalities identified between men and women about genetic diseases. You can read everything about the results in the magazine PNAS.

DNA includes genes expressed by RNA then before ultimately translating to proteins. Therefore, RNA is the intermediate product of the proteins that are present in our cells. "Our laboratory has designed an innovative technique, known as a specific RNA sequence on cellular allele, which means that RNA molecules can be cellular follow-up cells for the first time and not through tissue as a whole," Christelle Borel, a researcher in the Department of Genetics and Development, explained in the UNIGE Faculty of Medicine. This detailed analysis can be used to measure what is happening in each cell individually and, it follows, gene by gene.

The team led by Stylianos Antonarakis, a professor of emeritus in the Faculty of Medicine, investigated the random inactivity of one of the two chromosome X in women, discovered in 1960 by Mary F. Lyon. The British researcher was the first person to show that women have two chromosome X, unlike men, and one of them remains silent by a mechanism for correcting the gene dosage, compensating for a presence in women from an additional copy of the gene that is located on the X chromosome. In the 1990s, however, scientists found that some genes in the non-functional X chromosome avoid this inactivity. But how?

Permanent cell-by-cell non-functional

UNIGE researchers followed 935 skin cells and 48 blood cells of five different women so that they could analyze the phenomenon in more detail. "We solved the first cells and found the genes expressed in each cell," said Federico Santoni, former researcher at the UNIGE Department of Genetics and Development Department of Medicine and is now a researcher at the CHUV in Lausanne. "Then we followed the genome and the five daughters and with bioinformatics, we were able to find out what X chromosome was applied in every cell and it was quiet."

Until recently, the experimental techniques did not have the sensitivity needed to measure the gene expression rates that escaped inactive. Now, however, thanks to the experimental and bisexual approach developed by UNIGE, the genetics have identified 55 of these genes, including five that were still unknown. "Our main discovery was that no chromosome X in each cell was analyzed is 100% inactive, the rate ranges from cell to cell," remains Professor Antonarakis. The XIST gene expression initiates the inactivity of the X chromosome. "This gene produces small RNA molecules that surround one of both chromosome X, enforcing the genes on the This chromosome is to remain silent. We have shown that the XIST RNA molecules are more on this non-functional chromosome, the generity of its genes and the opposite. The expression of this gene explains the changing level of anactivation between the cells. "

Therefore, XIST is the key gene for non-active one of both X chromosome in female cells. But that's not the only one. "For the first time, we revealed five other genera that play an important role in the X-chromosome inactive mechanism," said Borel. "This will help us to understand what is happening at molecular level during inactivity. Even even more importantly, it means we can expand our investigations to learn more about the differences between men and Girls across a range of diseases. "

Inactivity X: a new understanding for genetic diseases?

There are many diseases that are caused by genes that have located on the X chromosome, such as hemophilia, intellectual disability syndromes and developmental disorders. "During our research, we also found that X-chromosome inactivity varies according to different cell life stages and by type of cell," added Antonarakis teacher. "This could count on the differences seen in the severity of certain diseases between patients, starting age and why some tissues are targeted by illnesses." Based on these results, researchers will be able to highlight the mechanisms behind genetic disease heterogeneity.


University of Genève. .

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