What is a gene variant and how do variants occur?
A gene variant is a permanent change in the DNA sequence of a gene, which can be inherited from parents or acquired throughout a person’s lifetime.
Overview
A gene variant is a permanent change in the DNA sequence that makes up a gene. While this type of genetic change was previously known as a gene mutation, the term "gene variant" is considered more accurate because changes in DNA do not always cause disease. These variants can affect one or more DNA building blocks, known as nucleotides, within a gene.
How Variants Occur
Gene variants generally fall into two categories based on how they are acquired:
- Inherited (Hereditary) Variants: These are passed from parent to child and are present in virtually every cell of the body throughout a person’s life. Because they are present in the parent’s egg or sperm cells—collectively called germ cells—they are also known as germline variants. When fertilization occurs, the resulting DNA contains variants from both parents.
- Non-inherited (Somatic) Variants: These occur during a person’s lifetime and are present only in specific cells, not every cell in the body. Because they typically occur in somatic cells (cells other than sperm and egg cells), they cannot be passed to the next generation. These may be caused by environmental factors, such as ultraviolet radiation from the sun, or by errors made during DNA replication in cell division.
De Novo Variants
Some genetic changes are described as de novo variants, meaning they are recognized in a child but not in either parent. These can occur in a parent’s egg or sperm cell, or shortly after the egg and sperm unite. As the fertilized egg divides, the variant is incorporated into every cell of the growing embryo. This explains genetic disorders where a child has a variant in every cell despite having no family history of the condition.
Mosaicism
Variants acquired during development can lead to mosaicism, where a set of cells has a different genetic makeup than others. This occurs anytime from embryonic development through adulthood.
- Somatic Mosaicism: Occurs when a proportion of somatic cells contain the variant while others do not. Depending on the variant and the number of cells affected, this may or may not cause health problems.
- Germline Mosaicism: Occurs when a proportion of egg or sperm cells contain a variant. In this situation, an otherwise unaffected parent can pass a genetic condition to their child.
Impact on Health
Most variants do not lead to disease, and those that do are uncommon in the general population. Some variants occur frequently enough to be considered common genetic variation; these are responsible for differences such as eye color, hair color, and blood type. While many of these common variations have no negative health effects, some may influence the risk of developing certain disorders.