Somatic Genetic Variants: A Genomic Revolution Hiding Inside Our Cells

Relevance: GS3 - Science and Technology- developments and their applications and effects in everyday life GS2 - Issues relating to development and management of Social Sector/Services relating to Health

(Source: The Hindu, 08/27/2023)

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Why in the news?

This article discusses somatic mutations in humans and the potential impacts that can result from these mutations, Awareness in the field of biotechnology

How do humans inherit traits?

• The human genome is made up of 23 pairs of chromosomes, one inherited from each parent.
• It acts as the blueprint for the genetic structure of humans which is carried from parent to child via the sperm and ovum.
• After fertilization, the combined single cell begins to divide and copy the genetic material repeatedly to nearly a trillion cells.
• Proteins that proofread and correct errors in the DNA ensure that the copying of DNA during the cell division process is extremely accurate.

‘Copy-paste’ mistakes

• However, studies have discovered that the process can have an error rate of 0.64-0.78 mutations per billion base pairs per division, which is minuscule considering the large size of the human genome.
• The rate and effect of such errors vary based on the stage of development or point of the life cycle.

Somatic Genetic Mutations

• A somatic genetic mutation refers to a mutation that occurs after birth but during development.
  • They are acquired after conception and are not passed on to future generations.
• It is influenced by the repeated copy-pasting of the genome i.e the rate of concurrence of somatic mutations will increase with age and the higher replacement of old cells by new cells i.e. tissue turnover.
• It is also known as a driver mutation as it can sometimes make a cell fitter than others.
• They are distinct from germline mutations, which are inherited from parents and are present in every cell of an individual’s body.
• They occur due to various factors, such as exposure to environmental mutagens like radiation or chemicals, errors in DNA replication, and other cellular processes.
• They can affect the DNA sequence of specific genes, leading to changes in protein production or function.

Mosaic of Cells

• Therefore, the human body can be viewed as a mosaic of cells instead of a clone of a single cell.
• Although these cells are similar in terms of their genomic composition, genetic variants mean there are differences.
• Some of these variants that lie in parts of the genome may be responsible for encoding or regulating proteins while others may not have any specific use.

Knowledge explosion

• Somatic genetic variations are important for a number of physiological processes performed by the body.
• Antibody-producing immune cells in the body undergo a number of somatic changes to produce diverse proteins that recognize and bind to specific pathogens, forming a ‘library’ of cells, each with a specific protein.
• When the body contracts an infection, it chooses cells that can bind best to the pathogen from these libraries to create antibodies.
• Although scientists have known about somatic variations for long, recent advancements in sequencing genetic matter in individual cells have contributed to a better understanding.
• Scientists have been able to study genes and the functional diversity of the human body’s cells using advanced microfluidics and high-throughput sequencers which can sequence tens of thousands of cells from a tissue at the same time.

Applications

• Cancer’s signatures: Some somatic changes can lead to the development of a cancer while in some cases, cancers can accelerate the development of somatic changes.
  • Therefore, somatic variations can aid in the early detection, diagnosis, and prognosis of cancers.
• Mutational signatures, i.e. certain genetic variations and patterns of genetic variations are characteristic of specific cancers.
  • This is used by most techniques for the early detection and diagnosis of cancers as these technologies detect DNA from tumor cells that have ‘escaped’ the cells into blood or fluids.
  • Similarly, certain variations in cancer could be used as a signature of the disease’s progress and/or to track how a tumor has responded to some course of therapy.
• Development of genetic diseases: Somatic genetic variants lead to numerous genetic diseases.
  • These diseases are not genetically inherited but occur due to genetic variations that arise during genetic development with the severity and distribution of the disease depending on how early or late during development the corresponding mutation occurred.
• Somatic genetic variants are an under-recognized cause of many immune disorders such as immunodeficiency disorders that result from mutations in a single gene.
• Beneficial impact: Somatic changes can change a deleterious change to a normal one through the phenomenon of revertant mosaicism.
  • Eg: Around 10% of Wiskott-Aldrich syndrome cases, a rare genetic immunodeficiency, have been found to have revertant mosaicism, which alleviates the severity of the disease in many cases

SMaHT Network

• The U.S. National Institutes of Health launched a programme called the ‘Somatic Mosaicism across Human Tissues’ (SMaHT) Network to understand somatic mosaicism and its biological and clinical significance.
• The SMaHT Network aims to discover somatic variants, develop tools and resources to study them, and improve the ability to analyze, interpret, and organize them.
• It uses a data-centric approach and has received $140 million in funding from the government of the U.S.A. to characterize somatic variants in 10-15 tissues from 150 post-mortem samples obtained from deceased individuals.

Conclusion

Such innovative approaches to understanding and managing the diseases that affect humans and the ability to scrutinize genes at the single-cell level will help reshape the world’s understanding of evolution.

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FAQs

MCQs

Question: At present, scientists can determine the arrangement or relative positions of genes or DNA sequences on a chromosome. How does this knowledge benefit us?

1. It is possible to know the pedigree of livestock
2. It is possible to understand the causes of all human diseases.
3. It is possible to develop disease resistant animal breeds.

Which of the statement(s) given above is/are correct? (UPSC CSE 2011)

(a)1 and 2 only

(b) 2 only

(c) 1 and 3 only

(d) 1, 2 and 3

Question: In the context of the developments in Bioinformatics, the term ‘transcriptome’, sometimes seen in the news, refers to

(a) a range of enzymes used in genome editing

(b) the full range of mRNA molecules expressed by an organism

(c) the description of the mechanism of gene expression

(d) a mechanism of genetic mutation taking place in cells

Question: What is the application of Somatic Cell Nuclear Transfer Technology?

(a) Production of biolarvicides

(b) Manufacture of biodegradable plastics

(c) Reproductive cloning of animals

(d) Production of organisms free of diseases