Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Uniparental Disomy (UPD) [Q99.9]

OMIM numbers: 608149, 176270, 105830

Dr. med. Imma Rost

Scientific Background

Uniparental disomy (UPD) is the term for inheritance of two copies (alleles) of a chromosome, or part of it, from only one parent. If the same parental chromosome is duplicated, this is called isodisomy; or heterodisomy if a pair of non-identical chromosomes is inherited from only one parent. Most chromosomes do not seem to be of pathological significance in this regard. Problems may arise if a mutation is present in a recessive gene on the chromosome which is inherited from one parent and this mutation then becomes homozygous in the child by isodisomy (duplication of this chromosome or gene) thereby causing a disease. Furthermore, if a chromosome or a chromosome region is affected which contains genes that are subject to what is known as genomic imprinting, i.e. the genes are active or inactive depending on parental origin. This, for instance, plays a role in the pathomechanism of the Prader-Willi and the Angelman syndrome. UPD diagnostics are also of practical significance in the context of prenatal diagnostics; for example, if chorionic villus sampling shows a mosaic for a trisomy of one of the chromosomes which is known to cause diseases in association with UPD. In this case, it is necessary to test if UPD is present in the fetus, for example due to trisomic rescue. If the original zygote was trisomic, i.e. contained two identical chromosomes from one parent and one chromosome from the other, a trisomic rescue can cause loss of the single chromosome copy of one parent; the two chromosomes of the other parent, however, remain. This state appears normal but may have pathological consequences.

In the case of Robertsonian translocations, e.g. involving chromosome 14 or 15, UPD has to be ruled out during prenatal diagnostics as well; however, the risk is estimated to be lower than 1%. The literature suggests that not only in association with the chromosomes shown in the table may UPD cause diseases, but also in association with chromosomes 2, 3, 16 and 20. Therefore, UPD should be ruled out during prenatal diagnostic procedures if a trisomy (or trisomy mosaic) is detected.