Uniparental Disomy (UPD)

Background and Standard Service Information

UPD is defined as the inheritance of both homologues of a pair of chromosomes from only one parent. The presence of both homologues is termed heterodisomy while the presence of two copies of one homologue is termed isodisomy. A mixture of both types is possible. UPD may arise through the following mechanisms:

UPD does not necessarily involve a whole chromosome; segmental UPD occurs due to somatic recombination between parental chromosomes before one of the events above.

The phenotypic consequences of UPD for several chromosomes are still unknown or poorly understood. UPD for some chromosomes e.g. chromosomes 13, 21, 22, 16, seems to have no effect or no constant effect on phenotype. Placental/foetal mosaicism is usually due to trisomy rescue and can cause severe growth retardation and possible developmental delay. UPD can cause reduction to homozygosity of autosomal recessively inherited mutations e.g. CF in UPD 7. However, most diseases associated with UPD are due to loss of the active homologue of an imprinted gene e.g. Prader Willi and Angelman syndromes, Beckwith Wiedemann syndrome. UPD in many cases is correlated with advanced maternal age (35 years and over), evidence that this is the result of meiotic non-disjunction. Referrals are usually as a result of cytogenetic findings in a patient e.g. chromosomal missegregations including confined placental mosaicism (CPM) and apparently balanced Robertsonian translocations or where unexpected homozygosity for a recessive allele is found. Referrals are usually made by a clinical geneticist.

Essential referral information

In addition to supplying standard patient identification and referral information, the following should be clearly indicated:

  1. Patient’s symptoms.
  2. Any family history, including names / dobs relationship, and genetic test results if available.
  3. Copy of cytogenetic report where relevant

It is the responsibility of the referring clinician to ensure consent has been obtained for testing and storage.

Samples required

Blood (3-5ml) in EDTA from the patient and both parents is required. Blood specimens must be appropriately packaged, and preferably sent by courier to arrive as soon as possible. Do not freeze prior or during postage.

Please note that extracted DNA is stored from patient’s samples at the National Centre for Medical Genetics, and kept indefinitely unless a written request for its disposal is received from the patient or their parent/guardian.

Restrictions on Testing

Testing would not normally be considered for asymptomatic children under age 16. A referral to a clinical geneticist may be suggested prior to testing.

Tests offered

Diagnostic tests are performed for patients where clinical symptoms and / or cytogenetic findings indicate the possibility of UPD. Analysis of polymorphic DNA markers distributed along the length of the chromosome under investigation is performed on DNA extracted from the proband and both parents.

Prenatal testing must be arranged in advance with the laboratory, through a Clinical Genetics department if possible.

Diagnostic sensitivity of tests

The sensitivity of such analysis is dependent on factors which are unique to each family assessed. As each polymorphic marker only tests a single point on the chromosome, it is never possible to exclude the presence of UPD at other points along the chromosome.


Following laboratory analysis, a report is prepared indicating the presence or absence of uniparental disomy and an interpretation of the result. Results are given in the form of a written interpretative report to the referring clinician.

Target reporting times

As reporting times are constantly evolving, please refer to molecular genetics, or contact the molecular genetics laboratory, to receive up-to-date information on anticipated reporting times for your referral.

Current target reporting times for each category of test offered (information correct as of 16/12/09):
Urgent samples (newborns and PNDs): 2 weeks
UPD: 3 months

Further tests

Samples may be sent to an external lab (Karin Buiting, Essen) for further analysis of the 14q32 imprinted region.

The NCMG Molecular Genetics laboratory participates in external QA schemes run by the UK NEQAS for Molecular Genetics, the European Molecular Genetics Quality Network (EMQN), and the Cystic Fibrosis European Network. Results of assessments are available for inspection upon request.

Document Number: DOC573, Revision Number 5