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

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

, or of part of a chromosome, from one parent and no copy from the other. 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 () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one co ...

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

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 an ...

children of consanguineous 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 cell The egg cell or ovum (: ova) is the female Reproduction, reproductive cell, or gamete, in most anisogamous organisms (organisms that reproduce sexually with a larger, female gamete and a smaller, male one). The term is used when the female game ...

s or sperm cells or may happen in early

fetal A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic stage, the fetal stage of development takes place. Prenatal development is a ...

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

homologous chromosome Homologous chromosomes or homologs are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during meiosis. Homologs have the same genes in the same locus (genetics), loci, where they provide points along e ...

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. Mos ...

) indicates a

error if the gene loci in question did not 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. Mos ...

) indicates either a meiosis II (if the gene loci in question did not 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 phenotypic trait, traits of an organism. The term covers the organism's morphology (biology), morphology (physical form and structure), its Developmental biology, develo ...

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

meiosis Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...

II, the

genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

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

disorders. UPD can 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. Offi ...

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

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

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

and

Angelman syndrome Angelman syndrome (AS) is a genetic disorder that affects approximately 1 in 15,000 individuals. AS impairs the function of the nervous system, producing symptoms, such as severe intellectual disability, developmental disability, limited to no ...

. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of chromosome 15.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 14 is also known to cause particular symptoms such as skeletal abnormalities, intellectual disability, 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 underreported.

All chromosomes

Genome wide UPD, also called uniparental diploidy, is when all chromosomes are inherited from one parent. Only in

mosaic A mosaic () is a pattern or image made of small regular or irregular pieces of colored stone, glass or ceramic, held in place by plaster/Mortar (masonry), mortar, and covering a surface. Mosaics are often used as floor and wall decoration, and ...

form can this phenomenon be compatible with life. As of 2017, there have only been 18 reported cases of genome wide UPD.

History

Eric Engel first proposed the concept of uniparental disomy in 1980 as both homologous chromosomes are inherited from one parent, with no contribution (for that chromosome) from the other parent. Eight years later in 1988, the first clinical case of UPD was reported and involved a girl with

cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...

and 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

s 2, 5–11, 13–16, 21 and 22.

References

External links