- Uniparental disomy (UPD) is a rare genetic condition where an individual inherits both copies of a chromosome or chromosomal region from one parent, rather than receiving one copy from each parent. This phenomenon can occur for any chromosome and may involve the entire chromosome or specific segments, leading to various clinical consequences depending on the chromosome involved and the parent of origin.
- There are two main types of UPD: isodisomy, where both copies of the chromosome are identical because they are derived from the same parental chromosome, and heterodisomy, where both copies come from the same parent but are different because they are derived from that parent’s two different chromosomes. These types can occur separately or as a mixture within the same chromosome.
- The formation of UPD can occur through several mechanisms. One common pathway is trisomy rescue, where a fertilized egg with three copies of a chromosome loses one copy to return to the normal diploid state. Another mechanism is monosomy rescue, where a fertilized egg with only one copy of a chromosome duplicates that chromosome to achieve the normal complement. Gamete complementation and post-fertilization error are other possible mechanisms.
- The clinical significance of UPD varies greatly depending on which chromosome is involved and whether the chromosomes come from the mother (maternal UPD) or father (paternal UPD). This variation in effects is largely due to genomic imprinting, where certain genes are expressed differently depending on their parental origin.
- Several well-characterized disorders are associated with specific UPD patterns. For example, paternal UPD of chromosome 15 causes Prader-Willi syndrome, while maternal UPD of the same chromosome can cause symptoms of Angelman syndrome. Other examples include Beckwith-Wiedemann syndrome (paternal UPD 11) and Temple syndrome (maternal UPD 14).
- The diagnosis of UPD typically requires molecular genetic testing. Methods may include microsatellite analysis, single nucleotide polymorphism (SNP) arrays, or methylation-specific testing, depending on the specific chromosome and region of interest. These tests can distinguish between isodisomy and heterodisomy and determine the parent of origin.
- Risk factors for UPD include advanced maternal age, which increases the risk of chromosomal nondisjunction during meiosis. Additionally, the presence of chromosomal rearrangements in parents can predispose to UPD formation in offspring. However, most cases occur sporadically with no identifiable risk factors.
- The reproductive implications of UPD vary depending on the underlying mechanism. In most cases, particularly those arising from trisomy rescue, the risk of recurrence in future pregnancies is low. However, if UPD resulted from an inherited chromosomal rearrangement, the recurrence risk might be higher.
- Treatment and management approaches for UPD-related disorders are typically focused on addressing specific symptoms and complications associated with the particular condition. This often requires a multidisciplinary approach tailored to the individual’s specific needs and the affected chromosome.
- Research continues to expand our understanding of UPD and its consequences. New technologies, particularly in genomic analysis, are revealing previously unrecognized cases and patterns of UPD, leading to better understanding of its frequency and clinical impact.
- Genetic counseling is crucial for families affected by UPD. This includes discussing the mechanism of occurrence, recurrence risks, and implications for family planning. The complexity of UPD and its various mechanisms makes professional genetic counseling particularly important.
- The impact of UPD on gene expression can be complex, particularly when it involves imprinted regions. The presence of isodisomy can also unmask recessive mutations, leading to unexpected manifestations of recessive disorders even when only one parent is a carrier.
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