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 error) or

isodisomy Isodisomy is a form of uniparental disomy in which both copies of a chromosome, or parts of it, are inherited from the same parent. It differs from heterodisomy in that instead of a complete pair of homologous chromosomes, the fertilized ovum cont ...

, 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 t ...

genes, a similar phenomenon seen in inbred 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 (plural ova), is the female 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 gamete is ...

s or sperm cells or may happen in early fetal development. It can also occur during

trisomic rescue Trisomic rescue (also known as trisomy rescue or trisomy zygote rescue) is a genetic phenomenon in which a fertilized ovum containing three copies of a chromosome loses one of these chromosomes (anaphase lag) to form a diploid chromosome complement. ...

. *When the child receives two (different) '' homologous chromosomes'' (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 meiosis I 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 Isodisomy is a form of uniparental disomy in which both copies of a chromosome, or parts of it, are inherited from the same parent. It differs from heterodisomy in that instead of a complete pair of homologous chromosomes, the fertilized ovum cont ...

(

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 meiosis II (if the gene loci in question didn't cross over) 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 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 resu ...

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 should be suspected in an individual manifesting a recessive disorder where only one parent is a

carrier Carrier may refer to: Entertainment * ''Carrier'' (album), a 2013 album by The Dodos * ''Carrier'' (board game), a South Pacific World War II board game * ''Carrier'' (TV series), a ten-part documentary miniseries that aired on PBS in April 20 ...

. Uniparental

inheritance Inheritance is the practice of receiving private property, Title (property), titles, debts, entitlements, Privilege (law), privileges, rights, and Law of obligations, obligations upon the death of an individual. The rules of inheritance differ ...

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 c ...

and

Angelman syndrome Angelman syndrome or Angelman's syndrome (AS) is a genetic disorder that mainly affects the nervous system. Symptoms include a small head and a specific facial appearance, severe intellectual disability, developmental disability, limited to no f ...

. 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 DNA ...

.Angelman Syndrome, Online Mendelian Inheritance in Man
/ref> *Other conditions, such as

Beckwith–Wiedemann syndrome Beckwith–Wiedemann syndrome (; abbreviated BWS) is an overgrowth disorder usually present at birth, characterized by an increased risk of childhood cancer and certain congenital features. A minority (97th centile) * Macroglossia * Hemihyperplas ...

, 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 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 Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

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 DN ...

. 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