Uniparental disomy occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other parent. UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes are inherited from one parent or isodisomy, in which a single chromosome from one parent is duplicated. Uniparental disomy may have clinical relevance for several reasons. For example, either isodisomy or heterodisomy can disrupt parent-specific genomic imprinting, resulting in imprinting disorders. Additionally, isodisomy leads to large blocks of homozygosity, which may lead to the uncovering of recessive genes, a similar phenomenon seen in inbred children of consanguineous partners. UPD has been found to occur in about 1 in 2,000 births.
When the child receives two homologous chromosomes from one parent, this is called a heterodisomic UPD. Heterodisomy indicates a meiosis I error if the gene loci in question didn't cross over.
When the child receives two replica copies of a single homologue of a chromosome, this is called an isodisomic UPD. Isodisomy indicates either a meiosis II or postzygotic chromosomal duplication.
A meiosis I error can result in isodisomic UPD if the gene loci in question crossed over, for example, a distal isodisomy would be due to duplicated gene loci from the maternal grandmother that crossed over and due to an error during Meiosis I, ended up in the same gamete.
A meiosis II error can result in heterodisomy UPD if the gene loci crossed over in a similar fashion.
Phenotype
Most occurrences of UPD result in no phenotypical anomalies. However, if the UPD-causing event happened during meiosis II, the genotype may include identical copies of the uniparental chromosome, leading to the manifestation of rare recessive disorders. UPD should be suspected in an individual manifesting a recessive disorder where only one parent is a carrier. Uniparental inheritance of imprinted genes can also result in phenotypical anomalies. Although few imprinted genes have been identified, uniparental inheritance of an imprinted gene can result in the loss of gene function, which can lead to delayed development, mental retardation, or other medical problems.
UPD has rarely been studied prospectively, with most reports focusing on either known conditions or incidental findings. It has been proposed that the incidence may not be as low as believed, rather it may be under-reported.
All chromosomes
Occasionally, all chromosomes will be inherited from one parent. As a result, recessive traits can be expressed.
History
The first clinical case of UPD was reported in 1988 and involved a girl with cystic fibrosis and unusually short stature who carried two copies of maternal chromosome 7. Since 1991, out of the 47 possible disomies, 29 have been identified among individuals ascertained for medical reasons. This includes chromosomes 2, 5–11, 13–16, 21 and 22.
