Introduction:
Uniparental disomy (UPD) is an abnormal condition when a child receives two copies of a chromosome, or a part of a chromosome, from one parent but no copies from the other. It can occur randomly during egg or sperm cell production or early fetal development. UPD has little impact on growth or health. Because most genes are not imprinted, it makes little difference whether a child receives both copies from one parent rather than just one from each. However, in some conditions, whether a gene is transmitted from a person's mother or father makes a difference. UPD patients may not have active copies of essential genes that undergo genomic imprinting. This loss of gene function might result in delayed development, intellectual impairment, or other health issues.
What Is The Example Of Uniparental Disomy?
UPD, or disruption of typical genomic imprinting, can lead to various genetic diseases. For example, disorders like Prader-Willi syndrome (PWS) and Angelman syndrome (AS) can be caused by uniparental disomy. An unusual facial appearance, small stature, significant intellectual incapacity by a lack of speech, stiff arm movements, and a spastic, uncoordinated walk characterize Angelman syndrome (AS). PWS is characterized by intellectual impairment, short stature, small hands and feet, obesity, and uncontrolled eating. Both of these conditions can result from UPD or other imprinting mistakes involving genes on the long arm of chromosome 15.
What Are The Types Of Uniparental Disomy?
There are two types of uniparental disomy, which are as follows:
-
Uniparental Isodisomy - When the homologs are identical, this is known as uniparental isodisomy. "uniparental isodisomy" refers to the similar nature of both chromosomes or chromosomal regions (typically the result of monosomy rescue by duplication).
-
Uniparental Heterodisomy - When inherited homologs differ, this is known as uniparental heterodisomy. The term "uniparental heterodisomy" means that the two chromosomes are separate members of a pair, yet both were inherited from the same parent. It is caused by a trisomy that is later reduced to disomy, resulting in two copies from one parent.
What Is The Phenotypic Result Of Uniparental Disomy?
The phenotypic result of UPD varies depending on the chromosome involved, the parent who provided the chromosomes, and whether it is isodisomy or heterodisomy. In uniparental disomy, three different phenotypic impacts are noticeable that including-
-
Those involving imprinted genes (e.g., the lack of a gene that generally manifests itself when inherited from parents of a particular sex).
-
Those involving the discovery of autosomal recessive diseases.
-
A vestige of aneuploidy causes those involving mosaicism.
Both chromosomes or regions in the pair are identical in uniparental isodisomy. It is essential if the parent carries an autosomal recessive disease. The defective gene will be present in 2 copies, and the phenotype will be that of the autosomal recessive condition if the offspring of a carrier parent has UPD with isodisomy for a chromosome that carries an aberrant gene; the child has an autosomal recessive disorder even though only one parent is a carrier of that recessive illness. Every human carries an estimated 20 defective autosomal recessive genes. Uniparental disomy cases have been associated with some autosomal recessive conditions, including spinal muscular atrophy, cystic fibrosis, cartilage-hair hypoplasia, thalassemia, and Bloom syndrome. A person with more than one recessive condition should explore the potential of uniparental isodisomy since the defective genes for both disorders may be carried on the same isodisomic chromosome.
How Does Uniparental Disomy Occur?
Uniparental disomy results from faulty meiotic segregation or a cell division defect that occurs during the production of eggs and spermatozoa. For example, nondisjunction during meiosis I results in the non-division of homologous chromosomes, resulting in heterodisomy; nondisjunction during meiosis II results in the non-division of sister chromatids, resulting in isodisomy. Here are some factors that result in UPD:
Gametic Complementation - A nullisomic gamete (a gamete with zero chromosomes for that particular autosome pair) matches a disomic gamete (an aberrant gamete with two chromosomes from the same parent). As a result, the embryo will only have one pair of autosomes from one parent.
Trisomy Rescue - A disomic gamete joins a normal gamete (a gamete with one chromosome) during conception. As a result, the zygote (i.e., embryo) will have three copies of that particular chromosome rather than two. The embryo will try to correct the issue by depleting one of the three copies: in two out of three situations, the patient will have a normal zygote, but in one out of three cases, they will get uniparental disomy.
Monosomy Rescue - A nullisomic gamete will contact an aberrant monosomal gamete (a gamete with only one chromosome) during fertilization. In this event, the embryo will try to rectify the condition by duplicating that one chromosome, resulting in isodisomy.
Other less common causes of UPD are as follows -
-
Postzygotic errors (errors that develop after fertilization and embryo formation due to mitotic recombination) generate segmental uniparental disomy.
-
Somatic replacement of a derivative or marker chromosome.
-
Irregularities in the structure of the chromosomes, such as reciprocal translocations, isochromosomes, and Robertsonian translocations.
What Is the Clinical Outcome Of Uniparental Disomy?
Chromosomes 6, 7, 14, 11, 15, and 20 may have phenotypic abnormalities even though uniparental disomy often has minimal clinical effects. It is because the genes on these chromosomes are imprinted or expressed differently depending on the parent from which they came. Therefore, imprinted genes have unique methylation patterns that are parent-specific epigenetic changes. After the first w of pregnancy, the methylation pattern is often finished and is maintained into adulthood. The methylation pattern determines whether the maternal or paternal chromosome copies will be expressed in the cell.
What Conditions Are Associated With Uniparental Disomy?
-
Paternal UPD 15 is associated with Angelman syndrome, but maternal UPD 15 is linked to Prader-Willi syndrome.
-
There is a link between Beckwith-Wiedemann syndrome and paternal UPD 11.
-
Maternal UPD 7 has been observed in some cases of Russell-Silver syndrome.
-
Paternal UPD 6 causes growth retardation (severe) and transitory newborn hyperglycemia.
-
Maternal UPD 16 is related to growth retardation and various congenital abnormalities, but the prognosis is generally favorable.
-
Temple and Kagami-Ogata syndromes, caused by UPD of chromosome 14.
Conclusion:
Most UPD studies lack the chromosomal component since uniparental disomy is diagnosed using molecular genetic techniques, and specialists view chromosomes as, at most, a whim of nature. UPD testing is investigated for patients with prenatally diagnosed mosaicism or Robertsonian translocations for clinically significant chromosomes and those with symptoms associated with uniparental disomy. DNA from the mother, father, and child or fetus should be tested using polymorphic markers.
