Study Shows One DNA Variant Can Overthrow Harmful Mutations, Explaining Varying Disease Severity

Researchers from the University of Lausanne and the Wellcome Sanger Institute have just published a new study in Molecular Systems Biology which uncovered how DNA can overcome genetic changes which are harmful to the body.

The discovery of the ability of DNA to suppress genetic changes which are undesirable could eventually lead to improved understanding of certain conditions. Specifically, it could illuminate why some rare disease patients, cancer patients, and patients with developmental conditions, have a more severe condition than others with the same diagnosis.

What is a Mutation?

Mutations change DNA, which influences the genetic code of organisms. Mutations can occur during cell division or through environmental experiences.

Most gene mutations are not very harmful. However, some can have extreme effects, leading to rare diseases or cancers.

Other mutations are positive. They encourage diversity and in many ways are a natural process of our evolution.

There are 6 billion letters of DNA within the human genome and therefore mutations are difficult to understand. Not only is each mutation complex, but one mutation can affect different individuals differently. Sometimes this is because one individual has another mutation which can counteract the negative change.

The Study

The researchers in this study investigated 1,106 alleles which were temperature-sensitive. These came from 580 genes within 10 wild yeast strains. The aim was to uncover if the yeast would grow when it was exposed to high temperatures.

They found 26% of undesirable gene mutations mutations were able to be suppressed by variants naturally occurring in a wild yeast strain. They examined 10 suppression cases in great detail.  For each mutation, one single additional mutation was able to cancel it out on its own. This mutation was called a “rescue mutation” as the other mutation could have potentially threatened survival.

Next, the yeast that did continue to grow were moved to the Wellcome Sanger Institute to uncover what specific mutation was able to suppress the allele which was temperature-sensitive.

Looking Forward

Considering that this research team only measured a small portion of yeast strains, the actual percentage of types of negative mutations which are able to be suppressed is likely significantly higher.

Further, because one singular mutation was able to rescue the organism, it could have extremely beneficial implications for future research.

The next step is to conduct this investigation within healthy human cells. This work has already gotten started at the Sanger Institute.

If the same finding is uncovered in humans, it could lead to many additional investigations in specific diseases, ultimately informing us regarding the best ways to treat little understood conditions.

You can read more about this investigation and its potential here.

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