Your DNA is organized into 23 pairs of chromosomes. One chromosome in each pair is inherited from your mother and the other from your father, and in most cases, the two chromosomes in each pair are very similar. The exception to this rule is the sex chromosomes, called X and Y. Females inherit one X chromosome from their mother and one X chromosome from their father, just like the other chromosomes. But males only have one X chromosome, which they inherit from their mother. Instead of a second X chromosome, males inherit a Y chromosome from their father.
X-linked recessive inheritance is an inheritance pattern that's specific for certain genetic variants found on the X chromosome. Since the number of X chromosomes a person has depends on his or her genetic sex, disease-causing variants found in genes on the X chromosome have different implications for males and females. For males (who only have one X chromosome), a single genetic variant is sufficient to cause an X-linked recessive condition. For females (who have two X chromosomes), a variant typically needs to be present on both copies of the X chromosome to cause the condition. Because it's less likely that females will have a variant on both X chromosomes, X-linked recessive conditions tend to occur more frequently in males than in females.
We'll use an X-linked recessive condition called G6PD deficiency as an example. G6PD deficiency is a common genetic condition characterized by episodes of anemia. It's caused by genetic variants in the G6PD gene, which is located on the X chromosome.
- Females typically have two X chromosomes, one from their mother and one from their father. If a female inherits just one disease-causing variant in the G6PD gene (from her mother or her father), she still has a "normal" version of the G6PD gene on her other X chromosome. In most cases, that normal version of the gene can compensate for having a disease-causing variant on the other chromosome. This means that most females with just one variant are not expected to develop symptoms of G6PD deficiency. In order to develop symptoms, most females need to inherit two variants (or two copies of a variant): one from their mother and one from their father.
- Males typically have only one X chromosome, which they inherit from their mother. (As mentioned above, males inherit a Y chromosome from their father.) If a male inherits a disease-causing variant in the G6PD gene from his mother, he doesn't have a normal version of the G6PD gene as a backup. This means that males with just one variant in the G6PD gene are at risk for developing symptoms of G6PD deficiency.
X-linked recessive inheritance also has implications for people who are considering having children. We'll continue using G6PD deficiency as an example.
- Females with a variant in the G6PD gene have a 50% chance of passing this variant on to each of their children. This is because females have two X chromosomes and pass a copy of one of those chromosomes on to each child. If a male child inherits this variant, he is at risk for developing symptoms of G6PD deficiency, regardless of whether his father has a variant. In most cases, female children who inherit this variant are not expected to develop symptoms of G6PD deficiency unless they also inherit a variant from their father.
- Males with a variant in the G6PD gene will pass this variant on to their female children but will not pass this variant on to their male children. (They pass a Y chromosome on to their male children.) Each of these female children will inherit a variant from their father. However, in most cases, they are not expected to develop symptoms of G6PD deficiency unless they also inherit a variant from their mother.
To summarize, males typically only have one X chromosome, so a single genetic variant is sufficient to cause an X-linked recessive condition. Females typically have two X chromosomes, so in most cases, a variant needs to be present on both copies of the X chromosome to cause the condition.