DNA mutations & # 39; undesirable & # 39; highly significant in autism and stroke

Non-coding DNA, unwanted DNA, dark genetic material – these are the names of the 98% of DNA that does not code directly for proteins, but plays a crucial role in the regulation of protein synthesis. It is now the subject of a new major study published in the journal Genetic nature.

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Genes are expressed as a function of the microenvironment of the cell and the body environment as a whole. This is achieved by multiple regulatory factors, affecting both the quantity and the quality of the proteins. Much of this modulation occurs via the production of RNA. Thus, an aberration of RNA regulation could seriously affect the expression of genes. For example, RNA regulation affects the brain's response to stroke and may also play a role in the cause of Autism Spectrum Disorder (ASD).

DNA is a large molecule found only inside the nucleus of the cell. On the other hand, RNA is a smaller and much more mobile molecule. One type of RNA is messenger RNA (mRNA). In the brain, mRNAs are at the level of synapses, or neuronal connections, and are the basis of protein production from the code of DNA. These proteins are involved in cerebral signaling. However, this production process, called translation, is also affected by microRNAs, another clbad of RNA, that can cause rapid or negative regulation of gene expression in response to changing conditions. in the brain.

A recent study by Robert Darnell, published in the newspaper Cell reports, involved monitoring microRNA activity in a mouse brain after a simulated stroke. They used cross-linking immunoprecipitation (CLIP) to monitor the activity of microRNAs and found that a type called miR-29 exhibited a sharp drop during a stroke. . Since miR-29 inhibits two proteins, namely GLT-1 and aquaporin, these proteins are found at higher levels in these subjects.

GLT-1 helps to eliminate excess glutamate from the brain during a stroke to limit brain damage. Therefore, higher concentrations help to speed up the recovery of stroke. Aquaporin concentrations, however, are directly related to swelling of the brain and its increase could therefore worsen the brain damage sustained during a stroke. It is therefore necessary to continue research to understand the dual role of a decrease in miR-29 in this situation and to develop better treatments for these processes.

Darnell said, "This research suggests potential targets for drugs to treat stroke. By artificially inducing more GLT-1 mRNA with a drug, for example, you can regulate the amount of glutamate aspirated and reduce brain damage. "

Another study looked at mutations of DNA in noncoding regions of the genome. The reason is that mutations in the coding genes, which cause the production of dysfunctional proteins, represent only a small fraction of the conditions. Thus, looking for a genetic basis for complex disorders such as ASD and seizures is often unpleasant and confusing. For example, many coding mutations are badociated with these diseases, but they contribute only about one-third of these cases. Thus, the response may be related to the regulatory mutant genes rather than the coding of DNA modifications. This could help explain why these disorders seem to have such unconventional patterns of transmission.

Darnell commented, "Some diseases have a genetic component, but they are not accompanied by simple family trees where it is possible to predict the risk that a child will contract a disease based on the genetic makeup of their parents. A different approach is needed to determine which types of mutations underlie the disease. "

To do this, Darnell's team examined the family tree of nearly 1,800 microfamilies, each consisting of one father and one mother and two children, one with and one without ASD. The DNA of each family was badyzed. A special in-depth learning algorithm was then developed to look for genetic differences between affected children and other family members. This allowed to discover how different genetic variants produce specific regulatory effects and negative consequences. In other words, de novo-occurring mutations in noncoding DNA in affected children, at the transcriptional and post-transcriptional level, had a much greater impact on normal function than mutations existing in other members of the family. These seem to be involved in the transmission of nerve impulses and in the development of neurons. Thus, coding and non-coding mutations contribute to ASDs.

The study indicates the possibility that a study of noncoding mutations will help to more clearly understand such complex disorders. Darnell said, "This dark genetic material can complement our understanding of the diseases that coding mutations can not explain."