X-linked inheritance

Sex chromosomes determine whether you are male or female

An individual’s sex (i.e., whether they are a male or female) is determined by the sex chromosomes. Most people have two sex chromosomes, one that is inherited from their mother and one that is inherited from their father. Typically, females have two X chromosomes (XX) and males have one X chromosome and one Y chromosome (XY). Conditions caused by changes (“mutations”) in genes located on the X chromosome are considered X-linked.

X-linked recessive inheritance

Most X-linked conditions are recessive. This means that in a person with two X chromosomes (most females), both copies of a gene (i.e., one on each X chromosome) must have a change or mutation whereas in a person with one X chromosome (most males), only one copy of a gene must have a mutation. A female with a mutation in one copy of a gene on the X chromosome is said to be a “carrier” for an X-linked condition. A male with a mutation in a gene on the X chromosome is typically affected with the condition. Because females have two copies of the X chromosome and males have only one X chromosome, X-linked recessive diseases are more common among males than females. However, X-linked recessive diseases can occur in both males and females.

For X-linked recessive disorders, an unaffected carrier mother who has a mutation in a gene on the X chromosome can transmit either the X chromosome with this mutation or a “normal” X chromosome to her children. If the father is unaffected, none of her daughters will be affected and all of her daughters will be unaffected—since they will inherit at least one normal X chromosome from their father. However, each daughter will have a 50% chance of being an unaffected carrier like her mother and a 50% chance of both X chromosomes being normal.

For X-linked recessive disorders, an affected father who has a mutation in a gene on the X chromosome can transmit either the X chromosome with this mutation or a Y chromosome to his children. If the mother is not affected or a carrier, none of his sons will be affected since they can only inherit a normal X chromosome from their mother and they inherit a Y chromosome from their father. Each daughter will have a 50% chance of being an unaffected carrier and a 50% chance of both X chromosomes being normal.

Example: Hemophilia A

Hemophilia A is an X-linked recessive disease caused by a lack of a coagulant, or blood clotting agent, called factor VIII (factor 8). This is caused by a mutation in a gene on the X chromosome called F8. If a father is affected, his daughters will be carriers of hemophilia A and his sons will be unaffected. If a mother is an unaffected carrier, each daughter has a 1 in 2 chance (i.e., 50%) of being an unaffected carrier and each son has a 1 in 2 chance (i.e., 50%) of being affected with hemophilia A.

X-linked Dominant Inheritance

For an X-linked dominant condition, only one copy of a gene on the X chromosome whether in a female with two X chromosomes or males with on X chromosome must have a change or mutation for an individual to be affected with the condition. For this reason, X-linked disorders are often seen with similar frequency in males and females. However, since females also have one normal X chromosome as well as an X chromosome with a mutation, the condition is often more “mild.” An example of an X-linked dominant disorder is Goltz Syndrome.