Ooc

Figure 2. Karyotype of a normal human male. Each of the first twenty-two chromosomes has two copies. The last set is the sex chromosomes, and consists of one X and one Y chromosome.

Dominant X-linked mutations, in which female carriers with just one mutated copy of the gene are affected, are rare. One example of such a disease is vitamin D-resistant rickets, in which people develop skeletal deformities. Generally, the disease is less severe in females than in males, because of X inactivation (see below). A famous X-linked disorder with inheritance that cannot be classified as either recessive or dominant is fragile X mental retardation. The fragile X chromosome bears its name because it displays a site susceptible to chromosome breakage. The mutated gene at the site contains a triplet repeat expansion, in which a series of three consecutive bases are copied multiple times. This causes the gene to be turned off by secondary changes in its structure. Affected males have severe mental retardation and female carriers can also be affected.

X Inactivation

X inactivation consists of the silencing of genes on one of the X chromosomes in the female fetus. This silencing, which results in the absence of protein products from the inactivated genes, restores equal X-linked gene expression between the sexes. So, in the end, females have only one active X chromosome, like males (Figure 1). In the case of individuals with an abnormal number of X chromosomes, such as three X chromosomes, only one X will remain active.

One may wonder then why females do not express deleterious recessive X-linked mutations like males. This is because X inactivation is random, and a female is a mosaic of cells with either her paternal X active or her maternal X active (Figure 1). Thanks to this randomness, female carriers usually deleterious harmful

0 0

Post a comment