Somatic Genetic Variants

General Science (UPPCS) Health and Diseases

Context: Scientists have known of somatic variants for many years, but recently there has been an explosion in the amount of data.

While DNA replication during cell division is generally accurate, errors occur at an estimated rate of 0.64-0.78 mutations per billion base pairs per division.
These mutations are more common during development and are referred to as somatic genetic mutations.
These errors, often arising from the repeated copying of the genome, increase with age and tissue turnover. Some of these mutations can confer advantages to cells, leading to the development of tumours known as driver mutations.

An error that occurs in the DNA after birth but during development is called a somatic genetic mutation.
The number and effect of these errors vary significantly, depending on the stage of development or the point in the life-cycle at which they occur.
Their occurrence is driven by the repeated ‘copy-pasting’ of the genome, which means there will be more somatic genetic mutations, the older an individual is and the higher the turnover of the tissue.
Turnover is the replacement of old cells with new ones.
Sometimes, a somatic genetic mutation can render a cell fitter than others, which lead to the formation of tumors.
So, these mutations are called driver mutations.

Somatic genetic variants are important for a number of normal physiological processes.
For example, the immune cells in our body, which produce antibodies, undergo an enormous somatic changes to create diverse proteins.
These proteins recognize and bind to specific pathogens, forming a ‘library’ of cells, each with a specific protein.
During an infection, the body selects cells from this library, depending on which can bind to a pathogen better, and uses them to make antibodies.

There has been rise in the amount of data and knowledge on somatic genetic variants due to our ability to sequence the genetic material in individual cells.
Using advanced microfluidics and high-throughput sequencers, scientists can now sequence many cells from a tissue at the same time, opening big windows into the genes in and the functional diversity of cells in the human body.

Somatic genetic variants play an important role in the development of cancers.
Somatic changes can cause a cancer to develop and that cancers can accelerate the development of somatic changes.
So, they can help with early detection, diagnosis, and prognosis.
Early detection and diagnosis of cancers rely on the fact that certain genetic variations and patterns, called mutational signatures, of genetic variations are characteristic of specific cancers.
There are technologies to detect DNA from tumor cells that has ‘escaped’ the cells into blood or fluids, to spot a cancer early.
Certain variations in a cancer could be used as a signature of the disease’s progress and to track how a tumor has responded to some course of therapy.

The other major application for somatic changes is in the development of genetic diseases.
Many genetic conditions arise from somatic genetic variants.
These conditions are not inherited from either parent but are due to new genetic variations that have arisen during development.
The severity and distribution of the disease depends on how early or late during development the corresponding mutation occurred.
Somatic genetic variants are an under-recognized cause of many immune disorders that are the result of mutations in a single gene, including primary immunodeficiency disorders.

Somatic changes can be beneficial in a genetic disease by changing a harmful mutation to a normal one, a phenomenon known as revertant mosaicism.
Around 10% of cases of Wiskott-Aldrich syndrome, a rare genetic immunodeficiency, have revertant mosaicism, thus alleviating the severity of the disease in many individuals.

Launched in the U.S. to understand the somatic mosaicism, discover somatic variants and the biological and clinical significance of such somatic events in humans.
It will help develop tools and resources to study them, and improve ability to analyse, interpret, and organise them in different biological and clinical contexts.