What are genomic imprinting and uniparental disomy?

Genomic imprinting and uniparental disomy are factors that influence how some genetic conditions are inherited.

Genomic Imprinting

People usually inherit two copies of each gene—one from the egg cell and one from the sperm cell. Both copies of each gene are usually active, or “turned on,” in cells. In some cases, however, only one of the two copies is turned on. Which copy is active depends on their origin: some genes are normally active only when they are derived from the sperm cell; others are active only when they are derived from the egg cell. This phenomenon is known as genomic imprinting.

In genes that undergo genomic imprinting, their origin is often marked on the gene during the formation of egg and sperm cells. This process, called methylation, is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. These molecules identify which copy of a gene was inherited from the egg cell and which was inherited from the sperm cell. The addition and removal of methyl groups can be used to control the activity of genes.

Only a small percentage of all human genes undergo genomic imprinting. Imprinted genes tend to cluster together in the same regions of chromosomes. Two major clusters of imprinted genes have been identified in humans: one on the short (p) arm of chromosome 11 (at position 11p15) and another on the long (q) arm of chromosome 15 (in the region 15q11 to 15q13).

Uniparental Disomy

Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells, or it may happen during early fetal development.

When UPD occurs, it often has no effect on health or development. Because most genes are not imprinted, it doesn’t matter if a person inherits both copies from one parent instead of one copy from each parent. In some cases, however, it does make a difference. A person with UPD may lack any active copies of essential genes that undergo genomic imprinting. This loss of gene function can lead to delayed development, intellectual disabilities, or other health problems.

UPD or a disruption of normal genomic imprinting can cause several genetic disorders. Prader-Willi syndrome and Angelman syndrome are two well-known examples of these conditions. Prader-Willi syndrome is characterized by behavioral problems and uncontrolled eating, and Angelman syndrome causes intellectual disabilities and impaired speech. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the q arm of chromosome 15. Other conditions, such as Beckwith-Wiedemann syndrome (a disorder characterized by accelerated growth and an increased risk of cancerous tumors), are associated with abnormalities of imprinted genes on the p arm of chromosome 11.