Harvard Medical School - Partners Healthcare Center for Genetics and Genomics
Inheritance
If something is said to be "inherited," it means it is passed on from one or both
parents to the child. Eye color, for example, is a trait that we inherit from our
parents. Mutations causing conditions like Noonan syndrome, hearing loss and
hypertrophic cardiomyopathy (HCM) also can be inherited.
How do mutations get passed on (inherited)?
There are four major ways that mutations can be passed on:
Autosomal refers to the fact that the mutation is located on one of the numbered
chromosomes (e.g. chromosome 5). When a mutation is passed in a dominant way, it
means that only one mutation is enough to cause the condition such as in HCM.
Therefore, if a person has one dominant mutation, they will have HCM. That also
means that every child of that person will have a 50% (or 1 in 2) chance of getting
the mutation and having HCM. The diagram below shows this relationship.
Facts about dominant conditions:
One mutation is enough to cause disease.
The disease is seen in every generation (e.g. grandparent, parent, child).
When one parent has a dominant mutation, every child has a 50% chance of having the disease (due to one mutation).
Autosomal still refers to the fact that the mutation is located on one of the numbered
chromosomes (e.g. chromosome 5). However, unlike a dominant mutation, a
recessive mutation is not enough to cause disease such as in cystic fibrosis (CF).
When an individual has just one recessive mutation, they are called a carrier.
A person who is a carrier 'carries' the mutation, but does not have CF.
For a person to have hearing loss from a recessive mutation, two mutations are
needed. This means that both parents must be carriers for a child to have two
mutations. The diagram below shows how CF is passed on.
Facts about recessive conditions:
Two recessive mutations are required to cause disease.
The disease may appear to skip generations.
If each parent has one recessive mutation (i.e. both parents are carriers), every child has a 25% chance of having CF and a 50% chance of being a carrier.
There are some mutations that occur in mitochondrial genes. These genes are found
inside organs called mitochondria, found within the cell.
Cell
Unlike nuclear genes, which are passed on by each parent, mitochondria are only
passed on by the mother. This means that if the mother has a hearing loss mutation in
her mitochondrial genes, all her children may have conditions like hearing loss. If
the father has a hearing loss mutation in his mitochondrial gene, his children will not
be affected. The diagram below demonstrates this inheritance.
Facts about mitochondrial hearing loss:
If the mother has a mitochondrial mutation, all of her children could develop the condition.
If the father has a mitochondrial mutation, he will not pass it onto any of his children.
Sometimes a mutation can occur only on a certain type of chromosome, called a sex
(or gender) chromosome. Sex chromosomes are just one pair of the 23 pairs of
chromosomes that we have.
sex chromosomes
This pair, however it is different in men and women. There are two types of sex
chromosomes, X and Y. Women have two X chromosomes, while men, have one X
and one Y chromosome.
These chromosomes look something like this:
If a mutation is said to be X-linked, it means it occurs only on the X chromosome.
Since women have two X chromosomes, if one X chromosome has a mutation, the
second chromosome can provide a normal copy of the gene, and disorders like
Danon disease will not develop. In men, the Y chromosome cannot make up for the
X-chromosome mutation in this way, so they will have Danon disease.
The diagram below shows how an X-linked mutation is passed on.
Facts about X-linked conditions:
Disease resulting from X-linked mutations are usually only seen in males.
If the mother has a mutation on one side of her X-chromosomes, each
female child has a 50% chance of being a carrier (but will not have the
condition) and each male child will have a 50% chance of having the
condition.
