Mosaicism

Females with a mutated gene on an X chromosome have two populations of cells. One group produces the intact protein, and the other produces a protein that is affected by the mutation. Like tortoiseshell cats, these females The tortoiseshell or calico cat is an example of mosaicism. This is caused by random X chromosome inactivation. A female has two X chromosomes. If she is heterozygous, one will carry the black allele, and one the orange allele. Random inactivation (X_i yields a population of cells with orange fur, and another population of cells with black fur. (The white colored fur seen in calico cats (that distinguishes them from tortoiseshell cats) is not associated with the X chromosome inactivation, rather, it is due to an autosomal gene.) are mosaic. Health sometimes depends on what fraction of the cells in a tissue express the functional gene.

For reasons that are not yet well understood, some females exhibit non-random inactivation patterns. If the chromosome with the normal copy of a gene is inactivated in most of the cells in a female's body, and if the normal protein is vital for some function, the female is likely to develop a disease.

With some X-linked diseases, cells that contain a mutation on the active X chromosome proliferate less during development than cells that carry themutation on the inactive X chromosome. In such cases, the female primarily expresses the normal gene.

Unlike females, males with an X-linked mutation will usually show signs of the disease, because they have no second functional copy. (Females will usually show symptoms if they inherit a mutated copy of the gene from each parent.) Males therefore inherit X-linked diseases, such as Duchenne muscular dystrophy, hemophilia, or colorblindness, much more commonly than females. Some X-linked disorders are almost never found in males, which may seem paradoxical until we consider that the absence of a functional gene can be so harmful that most males who inherit the disease die before being born.

Such is the case with Rett syndrome, an X-linked, dominant neurological disorder. This disorder is due to a mutation in a gene called MECP2. The disorder is primarily found in females, whose mosaicism gives them partial protection from its effects. Only a handful of males with Rett syndrome are known.