Inheritance patterns

Depending on where a mutation is located, and the kind of mutation it is, influences the likelihood of:

  1. Inheriting the mutation
  2. Being affected by the genetic condition as a result

For this reason, it is very useful for patients to understand the inheritance pattern of their mutation, so as to identify the risk of other family members having inherited the same mutation.

Below are some of the most commonly seen inheritance patterns:

When a mutation in a dominant allele is inherited, the cell will always express the mutated gene, and that individual will show symptoms of that particular genetic condition. We typically refer to this person as an “affected” individual.

So, when gametes are being made, and the chromosome pairs split into separate gametes, 50% of them will have the chromosome with the mutated dominant allele, and 50% will have the other, recessive allele. If an offspring inherits the dominant allele, they will be affected by the genetic condition, and be at risk of passing the mutation on to their own progeny. If they inherit the recessive allele, the individual will be unaffected, and have 0% risk of passing the mutation on.

To learn more about Autosomal Dominant Inheritance, click here to view a video by the Genomics Education Programme (NHS).

 

When a mutation in a recessive allele is inherited, the cell will not express that mutation in the presence of an unmutated allele, as the unmutated allele will be dominant. As such, protein is made from the DNA of the unmutated allele, and the individual shows no symptoms. This person is however what we refer to as a “carrier” – someone who is not affected by the genetic condition themselves, however can still pass the mutated allele on to offspring. As before, 50% of the individual’s gametes will possess the mutant recessive allele.

If both parents are carriers, and their offspring inherits the mutated recessive allele from both parents, then that offspring’s cells will have no option but to express the recessive allele and as such will be affected. In the case of two carrier parents, there is a 25% probability that their offspring will inherit both recessive alleles be affected by the condition. There is also a 25% probability that the offspring will inherit both dominant alleles, and will not carry the gene. The remaining 50% accounts for offspring that have inherited one dominant and one recessive gene from their parents. These offspring will be carriers, akin to their parents.

If only one parent is a carrier, there is 0% risk of their offspring developing genetic disease, however there is a 25% probability that their offspring will inherit the recessive allele from the carrier parent, and become a carrier themselves.

To learn more about Autosomal Recessive Inheritance, click here to view a video by the Genomics Education Programme (NHS).

Earlier we discussed X & Y sex chromosomes. Here we will explore how inheritance of mutations in these chromosomes differs from the other 22 pairs of chromosomes. When a genetic condition is X-linked recessive, that means that the mutation lies on the X chromosome, and primarily affects XY males, due to them possessing only one X chromosome.

If an XY male inherits a mutated X chromosome from their XX mother, they will develop the condition, because the Y chromosome does not possess an allele for that gene, and cannot prevent the cell from expressing the affected X chromosome. In the case of an XX carrier mother, and an unaffected XY father, offspring have a 50% risk of inheriting the affected chromosome. XY sons that inherit the mutated X chromosome will be affected by the genetic condition, while XX daughters will be unaffected carriers.

For XX females to be affected, both of their X chromosomes must have the mutated gene. One must come from an affected XY father and one from an XX carrier mother. However, due to a phenomenon called non-random X chromosome inactivation, female carriers may display some symptoms of the disease.

A small amount of our genome lies outside of chromosomes, in what we call mitochondrial DNA, Mitochondrial inheritance, also referred to as maternal inheritance applies specifically to genes contained within mitochondrial DNA.

Mitochondria are structures found within cells and responsible for producing energy for the cell. Egg cells and not sperm cells contribute mitochondria to a developing embryo and explains why only XX females can pass mitochondrial mutations to their children. These conditions can affect both males and females and can appear in every generation of a family, but XY fathers cannot 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.

This short audio-visual by Children’s national Hospital Rare Disease Institute helps to explain the phenomenon of Mitochondrial inheritance: Mitochondrial Inheritance.

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:

  1. The mutation may be a new event in that person,
  2. Other family members may have the same mutation, but may have not yet been diagnosed with the condition.
  3. Other family members may have a later age of onset, or have milder signs of the disease.

The mutation might also 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.