Central Idea

The human genome, comprising 23 pairs of chromosomes, is the blueprint of our genetic makeup inherited from our parents.
The replication of this genetic information in nearly a trillion cells during development results in a complex mosaic of cellular diversity.
Despite remarkable DNA replication accuracy, mutations still occur.

What are Somatic Genes?

Somatic genetic variants, also known as somatic mutations or somatic alterations, are genetic changes that occur in the cells of an organism’s body (somatic cells) during its lifetime.
These mutations are distinct from germline mutations, which are inherited from parents and are present in every cell of an individual’s body.
Somatic mutations are acquired after conception and are not passed on to future generations.
Somatic mutations can occur due to various factors, such as exposure to environmental mutagens (like radiation or chemicals), errors in DNA replication, and other cellular processes.
These mutations can affect the DNA sequence of specific genes, leading to changes in protein production or function.

Genetic Inheritance: Ovum and sperm carry parental genetic blueprints, which combine after fertilization.
Cell Division: The single fertilized cell, with 23 chromosomes, multiplies to form the human body’s trillions of cells.
DNA Replication Accuracy: Proteins proofread and correct DNA during replication, resulting in an error rate of 0.64-0.78 mutations per billion base pairs per division.

Dependent on Timing: Errors occurring after birth but during development are somatic genetic mutations.
Driver Mutations: Mutations that confer a fitness advantage to cells can lead to tumor formation and are called driver mutations.
Cellular Mosaic: Human body is a mosaic of cells with subtle genomic differences, influenced by somatic genetic variants.
Genetic Variants: Genetic variants within functional genome regions can affect protein encoding and regulation.

Immune Cell Diversity: Immune cells undergo extensive somatic changes to create diverse antibodies recognise pathogens.
Recent Knowledge Explosion: Technological advancements in sequencing individual cells have led to an explosion of data and knowledge on somatic variants.
Cancer’s Role: Somatic genetic variants play a significant role in cancer development, aiding in early detection, diagnosis, and prognosis.

Mutational Signatures: Specific genetic variations and patterns are characteristic of certain cancers, enabling early detection.
Blood-Based Detection: Technologies identify tumour DNA in blood to detect cancer early.
Disease Progress Tracking: Cancer variations can be used to monitor disease progression and therapy response.

Genetic Diseases Origin: Many genetic disorders arise from somatic genetic variants, not inherited from parents.
Disease Severity and Timing: The severity and distribution of genetic diseases depend on the timing of somatic mutations during development.
Immune Disorders: Somatic changes can cause immune disorders and even beneficially reverse some genetic diseases.

Somatic Mosaicism: US has launched the ‘Somatic Mosaicism across Human Tissues’ (SMaHT) Network.
Aims: SMaHT aims to discover somatic variants, develop tools for study, and improve analysis for biological and clinical insights.
Investment and Research: The U.S. government has invested $140 million to study somatic variants in post-mortem samples.

Cellular Complexity: Studying somatic variants reveals the intricate diversity of cells and reshapes evolutionary understanding.
Disease Management: Understanding somatic genetic changes can advance disease understanding and management.
Innovative Approaches: Analyzing genes at the single-cell level paves the way for innovative disease approaches and insights into evolution.