Uniparental disomy

Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. This genetic anomaly can lead to a variety of clinical outcomes, depending on the specific chromosomes involved and the genes located on those chromosomes. UPD can result in normal phenotypes, developmental delays, or congenital disorders, highlighting the importance of genomic imprinting and the parental origin of chromosomes in human development.

Mechanisms

UPD can arise through several mechanisms, including trisomic rescue, monosomic rescue, gamete complementation, and post-fertilization errors. Trisomic rescue, one of the most common mechanisms, occurs when a trisomic embryo (an embryo with three copies of a chromosome) loses one of the extra chromosomes, resulting in a diploid state. If the lost chromosome is from the same parent as the remaining two, UPD results. Monosomic rescue involves the duplication of a single chromosome from one parent to compensate for the absence of that chromosome from the other parent. Gamete complementation involves the fusion of two abnormal gametes, one with an extra chromosome and one missing the same chromosome. Post-fertilization errors, such as mitotic nondisjunction, can also lead to UPD.

Types

There are two main types of UPD: isodisomy and heterodisomy. Isodisomy occurs when the two chromosomes are identical copies of one another, often resulting from a post-zygotic duplication of a single chromosome. Heterodisomy involves the inheritance of two different homologous chromosomes from the same parent, typically arising from a meiotic error.

Clinical Significance

The clinical significance of UPD depends on the specific chromosomes involved and whether the condition disrupts genomic imprinting. Genomic imprinting is a genetic phenomenon in which certain genes are expressed in a parent-of-origin-specific manner. If UPD leads to the disruption of imprinted genes, it can result in various genetic disorders, such as Prader-Willi syndrome (PWS) and Angelman syndrome (AS). PWS and AS are both associated with UPD of chromosome 15, but the outcome depends on whether the UPD involves the maternal or paternal chromosome.

Diagnosis

The diagnosis of UPD is often challenging due to the variable phenotypes associated with the condition. It typically involves a combination of genetic testing methods, including karyotyping, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) array analysis. These tests can identify abnormalities in chromosome number and structure, as well as the parental origin of chromosomes.

Management

Management of UPD focuses on addressing the specific symptoms and complications associated with the condition. This may involve a multidisciplinary approach, including medical management of physical health issues, developmental support, and genetic counseling for the family. Early intervention and supportive therapies can improve the quality of life for individuals with UPD and their families.

Conclusion

Uniparental disomy is a complex genetic condition with significant implications for human health and development. Understanding the mechanisms, types, and clinical significance of UPD is crucial for the accurate diagnosis and management of affected individuals. Ongoing research into the genetic and epigenetic factors involved in UPD will continue to shed light on this fascinating area of genetics.