During X-inactivation, most genes on one of the X chromosomes of a female are inactivated in a mechanism that provides dosage compensation to equalize the level of gene expression of most X-linked genes in females to that of males who have only one X chromosome. This process, often called Lyonization, results in the formation of a Barr body, the highly compacted, inactive X chromosome. In the photograph, Barr bodies are shown by arrows. The form of DNA in the inactive X-chromosome is called heterochromatin.

In human females, one X chromosome or the other is inactivated in each cell early in development. As a result, some human female cells have one X chromosome active, while the rest of the cells have the other X chromosome active. Typically, X-inactivation is random, or near random, meaning that roughly half of a female's cells express the genes of one X chromosome and the other half of her cells express genes from the other X chromosome. However, in some females, X-inactivation is not random, but skewed. In cases of nonrandom, or skewed X-inactivation, all or most cells of a female express X-linked genes from a single X chromosome. In reality, nonrandom X-inactivation may be less representative of the process of X-inactivation than of reduced survival of cells with a particular X chromosome inactivated, making it appear that X-inactivation was nonrandom.

In some cases, females who carry X-linked genetic diseases can be affected by those diseases, if X-inactivation is not random. For example, if a structural abnormality disrupts the pattern of X-inactivation, then most or all of a female's cells will express genes from a single X chromosome. If there are genes that are disrupted by the structural abnormality, and those genes cause a disorder, the female can show symptoms of the disorder. For many X-linked disorders, females will show mild to moderate symptoms. This milder manifestation of an X-linked disorder in females may be related, in part, to the fact that most females have, in addition to a large number of cells expressing the abnormal gene, a large number of cells expressing the normal gene. Symptoms remain milder than those seen in affected males who carry no normal copy of the gene because they carry only a single X chromosome.

Some genes on the inactive X chromosome escape inactivation and remain active in females. These genes are believed to be responsible for many traits of normal females. The lack of these genes in females missing all or parts of a second X chromosome, as occurs in many cases of Turner syndrome, are thought to be associated with many of the clinical features of the syndrome.

There are two types of genetic heterogeneity: allelic and locus. Allelic heterogeneity occurs when different mutations in a single gene cause a particular disease. One disease that shows allelic heterogeneity is cystic fibrosis (CF). More than 1,000 different mutations have been identified in the gene associated with CF. Understanding allelic heterogeneity is important for interpreting DNA test results and predicting disease severity. Locus heterogeneity occurs when a particular disorder can be caused by mutations in more than one gene. Understanding locus heterogeneity is important for selecting  the proper DNA tests to order for a patient, interpreting DNA test results, predicting disease severity based on DNA test results, and predicting disease risk for family members.

X-inactivation, sometimes called Lyonization, occurs during embryogenesis and is the process by which most genes on one of the X chromosomes of a female are inactivated. This mechanism provides dosage compensation and equates the level of gene expression of most X-linked genes in females to that of males who have only one X chromosome. There are some X-linked genes in females that escape inactivation. X-inactivation usually occurs randomly within the cells of a female such that approximately half of the cells of a female express the genes from one of her X chromosomes and the other half of her cells express the genes from her other X chromosome. However, skewing can occur in X-inactivation. Skewed X-inactivation is observed when one of the X chromosomes of a female is preferentially inactivated in substantially more than half of her cells. In some cases, skewing of X-inactivation is extreme and may be caused by variations in the survival of cells in which a particular X chromosome is inactivated. Skewing of X inactivation can, in rare cases, cause X-linked diseases to be expressed in females.