Somatic genetic variants: A genomic revolution hiding inside our cells Premium

Scientists have known of somatic variants and their role in diseases for many years now, but there has been an explosion in the amount of data and knowledge only recently. This was due to our ability to sequence the genetic material in individual cells. Specifically, using advanced microfluidics and high-throughput sequencers, we can now sequence tens of thousands of 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.

The human genome has 23 pairs of chromosomes, one inherited from each of our parents. The genome is the blueprint of our genetic makeup. The ovum and the sperm carry these blueprints from our parents. After fertilisation, the combined single cell, with the 23 chromosomes, starts to divide, copying the genetic material over and over to nearly a trillion cells – which make up the human body.

As the cells divide, the DNA is copied with extremely high accuracy thanks to proteins that proofread and correct errors in the DNA. But despite this mechanism, various studies have estimated that there is still an error rate of 0.64-0.78 mutations per billion base pairs per division. But this rate is also minuscule given the large size of the human genome.

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. An error that occurs in the DNA after birth but during development is called a somatic genetic mutation. 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 tumours. So these mutations are called driver mutations.

Given these details, we should think of the human body as a mosaic of cells rather than as a clone of a single cell. In their genomic composition, these cells are similar to each other, but still different enough thanks to a handful of genetic variants. While most of these variants may not have a function, a small number will if they lie in parts of the genome responsible for encoding proteins or regulating them.

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 amount of somatic changes to create diverse proteins. These proteins recognise 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.

Scientists have known of somatic variants and their role in diseases for many years now, but there has been an explosion in the amount of data and knowledge only recently. This was due to our ability to sequence the genetic material in individual cells. Specifically, using advanced microfluidics and high-throughput sequencers, we can now sequence tens of thousands of 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.