A gene variant is a permanent change in the DNA sequence that makes up a gene. This type of genetic change used to be known as a gene mutation, but because changes in DNA do not always cause disease, it is thought that gene variant is a more accurate term. Variants can affect one or more DNA building blocks (nucleotides) in a gene.
Gene variants can be inherited from a parent or occur during a person’s lifetime:
- Inherited (or hereditary) variants are passed from parent to child and are present throughout a person’s life in virtually every cell in the body. These variants are also called germline variants because they are present in the parent’s egg or sperm cells, which are also called germ cells. When an egg and a sperm cell unite, the resulting fertilized egg cell contains DNA from both parents. Any variants that are present in that DNA will be present in the cells of the child that grows from the fertilized egg.
- Non-inherited variants occur at some time during a person’s life and are present only in certain cells, not in every cell in the body. Because non-inherited variants typically occur in somatic cells (cells other than sperm and egg cells), they are often referred to as somatic variants. These variants cannot be passed to the next generation. Non-inherited variants can be caused by environmental factors such as ultraviolet radiation from the sun or can occur if an error is made as DNA copies itself during cell division.
Some genetic changes are described as new (de novo) variants; these variants are recognized in a child but not in either parent. In some cases, the variant occurs in a parent’s egg or sperm cell but is not present in any of their other cells. In other cases, the variant occurs in the fertilized egg shortly after the egg and sperm cells unite. (It is often impossible to tell exactly when a de novo variant happened.) As the fertilized egg divides, each resulting cell in the growing embryo will have the variant. De novo variants are one explanation for genetic disorders in which an affected child has a variant in every cell in the body, but the parents do not, and there is no family history of the disorder.
Variants acquired during development can lead to a situation called mosaicism, in which a set of cells in the body has a different genetic makeup than others. In mosaicism, the genetic change is not present in a parent’s egg or sperm cells, or in the fertilized egg, but happens later, anytime from embryonic development through adulthood. As cells grow and divide, cells that arise from the cell with the altered gene will have the variant, while other cells will not. When a proportion of somatic cells have a gene variant and others do not, it is called somatic mosaicism. Depending on the variant and how many cells are affected, somatic mosaicism may or may not cause health problems. When a proportion of egg or sperm cells have a variant and others do not, it is called germline mosaicism. In this situation, an unaffected parent can pass a genetic condition to their child.
Most variants do not lead to development of disease, and those that do are uncommon in the general population. Some variants occur often enough in the population to be considered common genetic variation. Several such variants are responsible for differences between people such as eye color, hair color, and blood type. Although many of these common variations in the DNA have no negative effects on a person’s health, some may influence the risk of developing certain disorders.