Imprinting and Uniparental Disomy Practice

For an imprinting problem, track both which chromosome region is involved and which parent supplied the relevant contribution. A normal copy number does not establish a normal parent-of-origin pattern.

Separate copy number from parent of origin

Genomic imprinting involves parent-dependent gene activity. Uniparental disomy (UPD) means both copies of a chromosome or relevant region come from one parent. These concepts are related, but neither is a synonym for a deletion.

• In heterodisomy, the contribution includes two different homologues from one parent.
• In isodisomy, a contribution includes two copies of the same parental homologue or segment.

Actual results can be more complex or mixed. Isodisomy can also matter when it makes a recessive variant homozygous, even outside a recognized imprinted region.

Practice case: Can normal copy number exclude an imprinting disorder

A child has Prader-Willi syndrome. Testing shows two copies of chromosome 15, both inherited from the mother. Which mechanism best explains the condition despite the normal copy number?

1. Loss of the usual expression of paternally expressed genes in the Prader-Willi critical region.
2. Loss of maternal UBE3A expression in neurons, as in Angelman syndrome.
3. Biallelic pathogenic sequence variants in a recessive gene in the region.
4. Increased chromosome 15 dosage, as in trisomy 15.

Answer: A. Maternal uniparental disomy leaves the child without the usual paternal contribution at the imprinted Prader-Willi region. Two chromosome copies do not guarantee the expected parent-specific gene expression. B describes a different imprinting disorder; C is a different disease mechanism; D would involve an extra chromosome copy rather than the two copies specified here.

Prader-Willi syndrome GeneReviews

Follow the mechanism through to testing

Ask whether the assay assesses dosage, methylation, parental origin, or sequence. A methylation result may establish an abnormal imprinting pattern without fully identifying whether the cause is a deletion, uniparental disomy, or an imprinting defect. That distinction can affect recurrence counseling.

Avoid memorizing one recurrence number for every person with the same syndrome label. Establishing the molecular mechanism is part of answering the family-risk question. Use the test-selection guide to compare assays.

EveryGene Academy offers application practice, and 101 Must-Know Genetic Conditions flashcards can support condition review. The free Pedigree Workbook offers additional family-risk practice.

Sources: Prader-Willi syndrome GeneReviews; MedlinePlus on imprinting and inheritance. A methylation result may not identify the underlying cause.

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