What is a Gene Mutation?

A gene mutation or variant is a permanent change in the DNA sequence that a gene is made of, making the sequence different from what is found in most people. Variants can be small enough to affect a single DNA base pair, or large enough to affect a wide segment of a chromosome that includes multiple genes. These changes can be harmful, beneficial, or have no effect.¹

Most disease-causing gene variants are uncommon in the general population, although other genetic changes occur more frequently. Genetic alterations that occur in more than 1% of the population are called polymorphisms, and are common enough to be considered a normal variation in the DNA. Polymorphisms are responsible for many of the normal differences between people including eye color, hair color, and blood type. While many polymorphisms have no negative effects on a person’s health, some of these variants may increase a person’s risk of developing certain disorders.²

There are two major types of gene variants¹:

• Hereditary, also known as germline mutations or variants, are those that are inherited from one or both parents and are present in virtually every cell in the body throughout a person’s life.
  • These variants were present in the parent’s egg or sperm cells, which are also called germ cells.
  • In human reproduction, when a sperm cell combines with an egg cell, the resulting fertilized egg cell receives DNA from both parents.
  • If there is a variant in the DNA, that variant will be present in each of the cells of the child that grows from the fertilized egg.
• Acquired (or somatic) mutations arise at some time during a person’s life and are typically present only in certain cells, not in every cell in the body.¹
  • These changes can result from environmental stressors such as ultraviolet radiation from the sun, or from an error in DNA replication during cell division.
  • Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed to the next generation.

Some genetic changes are classified as de novo (new) variants, which can be either hereditary or somatic.¹

• In some cases, a de novo variant may arise in a person’s egg or sperm cell but is not present in any of the person’s other cells.
• In other cases, a de novo change may take place in the sperm, or in the fertilized egg shortly after the egg and sperm cells combine, though it is often impossible to pinpoint exactly when a de novo change occurred.
• As the fertilized egg divides, the variant may be present in each resulting cell in the growing embryo.
• When a child with a genetic condition has a variant in every cell in the body but the parents do not, and there is no family history of the condition, the condition may be due to a de novo change.