Hemophilia Allele

In humans, the X chromosome is rather large and carries many genes, while the Y chromosome is quite small and has relatively few genes. Therefore, many genes are found on the X chromosome but not on the Y; these are known as X-linked genes. By comparison, only a few genes are known to be Y linked, meaning that they are found on the Y chromosome but not on the X. The term sex linked refers to genes that are found on one sex chromosome but not on the other. Because few genes are found on the Y chromosome, the term sex-linked genes usually refers to X-linked genes.

In mammals, a male cannot be described as being homozygous or heterozygous for an X-linked gene, because these terms describe genes that are present in two copies. Instead, the term hemizygous is used to describe the single copy of an X-linked gene in a male. Many recessive X-linked mutant alleles cause diseases in humans, and these diseases occur more frequently in males than in females. Why?

As an example, consider the X-linked recessive disorder called classical hemophilia (hemophilia A). In individuals with hemophilia, blood does not clot normally and a minor cut can bleed for a long time. Small bumps can lead to large bruises because broken capillaries leak blood profusely into surrounding tissues before the capillaries are repaired. Common accidental injuries pose a threat of severe internal or external bleeding for people with hemophilia. Hemophilia A is caused by a recessive X-linked disease allele that encodes a defective form of a clotting protein. If a mother is a heterozygous carrier of hemophilia A, each of her children has a 50% chance of inheriting the recessive allele. A Punnett square shows a cross between a normal father and a heterozygous mother. Xh ? A is the chromosome that carries the recessive allele for hemophilia A.

Although each child has a 50% chance of inheriting the hemophilia allele from the mother, only sons will exhibit the disorder. Because sons do not inherit an X chromosome from their fathers, a son who inherits the abnormal allele from his mother will have hemophilia. However, a daughter who inherits the hemophilia allele from her mother will also inherit a normal allele from her father. This daughter will have a normal phenotype, but if she passes the abnormal allele to her sons they will have hemophilia.