What are the different ways a genetic disease may be inherited?
Autosomal Dominant Inheritance
Autosomal dominant inheritance occurs when just one copy of a gene mutation is enough to cause an individual to be affected by the condition. The mutation can lead to development of the condition even when the second copy of the gene is normal. Each affected person usually has one affected parent, and these disorders tend to occur in every generation of an affected family.
Both males and females can be affected, however some may be affected so mildly that they may not even be aware that they have signs of the disease. In rare cases, someone with a dominant mutation may not show any signs of the condition. In autosomal dominant inheritance, each affected individual has a 50% chance with each pregnancy of having a child affected by the condition.
Autosomal Recessive Inheritance
In autosomal recessive inheritance, on the other hand, a person develops the condition only when both copies of the gene don’t work. That is, the gene from the mother and the gene from the father both have mutations and the affected person inherited one gene mutation from each parent.
Typically, only one generation is affected and both males and females can be affected. In this type of inheritance people with one mutated copy of the gene do not have the condition, but they are called ‘carriers’. When both parents are carriers, there is a 25% chance with each pregnancy that they child will have the condition.
X-linked Recessive Inheritance
In X-linked recessive inheritance, the mutation is on the X chromosome. Males have an X and a Y chromosome and females have two X chromosomes. Because males have only one X chromosome, if they inherit a disease mutation on that chromosome, they will develop the condition. Females with one mutation and one regular copy of the gene typically do not show signs of disease, although due to the phenomenon of non-random X chromosome-inactivation, some female carriers may display symptoms.
In families, multiple generations of affected males are observed, connected through unaffected females. For example, an affected grandfather might have a daughter who is a carrier and she may then have a son who is affected. When a male is affected, all of his daughters will be carriers and none of his sons will be affected. When a female is a carrier, each daughter has a 50% chance of being a carrier and each son has a 50% chance of being affected.
Mitochondrial inheritance, also known as maternal inheritance, applies to genes contained within mitochondrial DNA. Mitochondria are structures within each cell that convert molecules into energy. Because only egg cells and not sperm cells contribute mitochondria to a developing embryo, only females pass on mitochondrial mutations to their children. These conditions can affect both males and females and can appear in every generation of a family, but fathers do not pass down these conditions to their children. The severity of symptoms may vary from one affected individual to another; even within the same family due to a ‘dosage’ effect. This is due to the fact that we have many mitochondria in each cell. In one individual, if only a small proportion of mitochondria in each cell have the mutation, symptoms will be mild. In another individual, if a higher proportion of mitochondria in each cell carry the mutation, symptoms will be more severe.
Very often, a person diagnosed with an inherited condition has no other family members with the disease. There are several possible reasons for only finding one person affected in the family. The mutation may be a new event in that person, or other family members may have the same mutation, but may have not yet been diagnosed with the condition. They may have a later age of onset, or have milder signs of the disease. The mutation might have been in the family for a long time, but by chance, no other family members have been affected. For autosomal recessive disease, carriers may have been present in the mother’s and father’s side of the family for several generations, but a child won’t develop a condition unless both parents are carriers and both pass on a mutation to their child.