An autosomal dominant disorder is a genetic condition that occurs due to a mutation in just one copy of a specific gene. This means that inheriting a single altered gene from one parent is sufficient to cause the condition. The term “autosomal” signifies that the affected gene is located on one of the 22 numbered chromosomes, known as autosomes, rather than on the sex chromosomes (X or Y). These disorders are passed down through families, and a person with such a condition has one parent who also carries the mutated gene.
Understanding Dominant Genetic Inheritance
Our genetic information is organized into chromosomes, with humans having 23 pairs. Twenty-two of these pairs are autosomes, which are the same in both males and females, while the final pair consists of sex chromosomes. Each chromosome contains thousands of genes, which are segments of DNA that provide instructions for making proteins and performing various functions in the body. For each gene, we inherit two copies, or alleles, one from each parent.
The term “dominant” in this context refers to the nature of the mutated gene’s expression. Even with a normal, functioning copy of the gene present from the other parent, the single altered copy overrides it and causes the associated trait or disorder to manifest. This is different from a recessive condition, where a person would need to inherit two copies of the mutated gene, one from each parent, for the disorder to appear.
The inheritance pattern often means the disorder can be seen in multiple generations of a family. If a parent has an autosomal dominant condition, they possess one mutated allele and one normal allele. During reproduction, the parent will pass on only one of these two copies to their child. The specific allele that is passed on is random, creating a predictable probability for inheritance.
It is also possible for an autosomal dominant disorder to appear in an individual without any family history, an event known as a de novo mutation. This means the genetic change occurred for the first time in the sperm or egg cell of a parent, or during the very early stages of embryonic development. In these instances, the affected individual is the first in their family to have the condition and can then pass it on to their own children.
Probability of Passing on the Gene
When one parent has an autosomal dominant disorder, there is a predictable probability of passing the condition to their offspring. For each pregnancy, a child has a 50% chance of inheriting the mutated gene and being affected by the disorder. This also means there is an equal 50% chance the child will inherit the normal gene and not have the disorder.
This probability can be visualized using a Punnett square. If one parent has one copy of the mutated gene (represented as “A”) and one normal copy (“a”), and the other parent has two normal copies (“aa”), the potential combinations for their child are “Aa” or “aa”.
This 50% risk is independent for each pregnancy. The outcome of a previous pregnancy does not influence the outcome of any future pregnancies. For example, if a couple’s first child inherits the disorder, the chance of their second child also inheriting it remains 50%.
Children who do not inherit the mutated gene will not have the disorder and cannot pass it on to their own offspring. They have inherited the normal copy of the gene from the affected parent and a normal copy from the unaffected parent. Therefore, the chain of inheritance for that branch of the family is broken.
Examples of Autosomal Dominant Disorders
Several well-known genetic conditions follow an autosomal dominant inheritance pattern. These disorders can affect various parts of the body and have a wide range of signs and symptoms.
- Huntington’s disease is a neurodegenerative disorder that typically manifests in adulthood. It is caused by a mutation in the HTT gene, which leads to the progressive breakdown of nerve cells in the brain, affecting a person’s movement, cognitive abilities, and psychiatric state.
- Marfan syndrome is another example of an autosomal dominant disorder, affecting the body’s connective tissue. This condition is caused by mutations in the FBN1 gene, and because connective tissue is found throughout the body, Marfan syndrome can affect the heart, blood vessels, bones, joints, and eyes.
- Achondroplasia is the most common form of dwarfism. It is caused by a mutation in the FGFR3 gene, which is involved in converting cartilage to bone. This results in a short stature, particularly in the limbs, while the torso is of average size.
- Neurofibromatosis type 1 (NF1) is a condition that causes tumors to grow on nerve tissue. These can include tumors on the skin, under the skin, and along nerves in the brain and spinal cord. The condition is caused by a mutation in the NF1 gene, which is supposed to produce a protein that acts as a tumor suppressor.