Uniparental disomy (UPD) occurs when a person receives two copies of a

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

, 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 (an earlier stage

meiosis I Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately res ...

error) or isodisomy, in which a single chromosome from one parent is duplicated (a later stage

meiosis II Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately res ...

error). 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 Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. ...

, which may lead to the uncovering of

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genes, a similar phenomenon seen in

inbred Inbreeding is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically. By analogy, the term is used in human reproduction, but more commonly refers to the genetic disorders and o ...

children of

consanguineous Consanguinity ("blood relation", from Latin '' consanguinitas'') is the characteristic of having a kinship with another person (being descended from a common ancestor). Many jurisdictions have laws prohibiting people who are related by blood fro ...

partners. UPD has been found to occur in about 1 in 2,000 births.

Pathophysiology

UPD can occur as a random event during the formation of egg cells or

sperm cells A spermatozoon (; also spelled spermatozoön; ; ) is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote. (A zygote is a single cell, with a complete set of chromosomes, ...

or may happen in early

fetal A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...

development. It can also occur during trisomic rescue. *When the child receives two (different) ''

homologous chromosome A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same loci where they provide points alon ...

s'' (inherited from both grandparents) from one parent, this is called heterodisomic UPD. Heterodisomy (

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

) indicates a

error if the gene loci in question didn't cross over. *When the child receives two (identical) replica copies of a single ''homologue'' of a

, this is called an isodisomic UPD. Isodisomy (

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

) indicates either a

(if the gene loci in question didn't cross over) or postzygotic

chromosomal duplication Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene ...

. *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 In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological prop ...

anomalies. However, if the UPD-causing event happened during

meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately r ...

II, the genotype may include identical copies of the uniparental chromosome (isodisomy), leading to the manifestation of rare

disorders. UPD should be suspected in an individual manifesting a recessive disorder where only one parent is a carrier. Uniparental

inheritance Inheritance is the practice of receiving private property, titles, debts, entitlements, privileges, rights, and obligations upon the death of an individual. The rules of inheritance differ among societies and have changed over time. Officia ...

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, intellectual disability, or other medical problems. *The most well-known conditions include

Prader–Willi syndrome Prader–Willi syndrome (PWS) is a genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, those affected become ...

and Angelman syndrome. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of

chromosome 15 Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 102 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DN ...

.Angelman Syndrome, Online Mendelian Inheritance in Man
/ref> *Other conditions, such as Beckwith–Wiedemann syndrome, are associated with abnormalities of imprinted genes on the short arm of

chromosome 11 Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

. *

Chromosome 14 Chromosome 14 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 14 spans about 107 million base pairs (the building material of DNA) and represents between 3 and 3.5% of the total DNA ...

is also known to cause particular symptoms such as skeletal abnormalities,

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...

, and joint contractures, among others. 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

Genome wide UPD, also called uniparental diploidy, is when all chromosomes are inherited from one parent. Only in mosaic form can this phenomenon be compatible with life. As of 2017, there have only been 18 reported cases of genome wide UPD.

History

The first clinical case of UPD was reported in 1988 and involved a girl with cystic fibrosis and short stature who carried two copies of maternal

chromosome 7 Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 159 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total D ...

. Since 1991, out of the 47 possible disomies, 29 have been identified among individuals ascertained for medical reasons. This includes

s 2, 5–11, 13–16, 21 and 22.

References

External links