Uniparental Disomy

Uniparental disomy refers to the phenomenon whereby an individual receives both pairs of a specific chromosome (or portion of a pair) from one parent and no copy from the other parent.

If the two homologues are identical (replica copies of the same homolog) and from the same parent this is referred to as uniparental isodisomy. Such errors occur during meiosis II or postzygotic duplication.

If the two homologues are different (heterozygous) but from the same parent, this is referred to as uniparental heterodisomy (this indicates an error in meiosis I). Thus far uniparental disomy (UPD) has been documented for more than 18 of the 22 autosomes, both X chromosomes Opens in new window, and the XY pair (Engel and Antonarakis, 2001).

The most common mechanism is through trisomy rescue (the loss of a chromosome from an initial trisomy). This involves the original meiotic error leading to trisomy and then the mitotic error in which the normal diploid state is returned through non-disjunction or anaphase lag. This has mostly been observed in maternally derived isodisomy occurring during oogenesis (Engel and ANtonarakis, 2001).

Engel and Antonarakis (2001) provide a fascinating discussion of uniparental disomy, the diseases identified to date, and the complex genetic discussion of uniparental disomy, the diseases identified to date, and the complex genetic counseling issues.

Several genetic conditions have been described in which UPD has been observed. For example, a new individuals with classic autosomal recessive cystic fibrosis have inherited both chromosomes from the cystic fibrosis mutation from one parent (the other parent has two normal alleles).

Uniparental disomy has been observed in 2–3% of individuals with Angelman syndrome Opens in new window in which the child inherits two critical regions of chromosome 15s from the mother and thus has Prader Willi syndrome Opens in new window.

For some chromosomes, uniparental disomy may produce no effect, and for other chromosomes it may be lethal.

Uniparental disomy can cause morbidity or lethality by altering imprinting processes, mimicking disease deletions or duplications, generating recessive disorders when only one parent is a carrier, or prompting malignant tumor development (Engel, 1995).

Although misattribution of paternity is the most likely explanation if a child with a classic autosomal recessive condition has only one parent identified as a mutation carrier, uniparental disomy should be a consideration.

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