# Uniparental Disomy > Uniparental disomy for MBBS Pathology: both chromosomes from one parent, trisomy rescue, Prader-Willi, Angelman, Beckwith-Wiedemann and isodisomy. - Canonical URL: https://prepelephant.com/topics/mbbs/pathology/uniparental-disomy - Exam / course: MBBS · Subject: Pathology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Uniparental Disomy", PrepElephant, https://prepelephant.com/topics/mbbs/pathology/uniparental-disomy ## Direct answer Two copies of chromosome 15, both inherited from the mother, with no deletion anywhere — this is uniparental disomy (UPD), the situation in which both members of a chromosome pair descend from a single parent, and it produces Prader-Willi syndrome because the paternally expressed genes on 15q are silenced on maternal copies. UPD matters through two distinct mechanisms: it disturbs imprinting (the same chromosome, wrong parental origin — Prader-Willi, Angelman, Beckwith-Wiedemann, Russell-Silver syndromes) and, when isodisomic, it renders the carrier homozygous for recessive alleles carried by one parent alone. The commonest route is trisomy rescue — a trisomic conception losing one chromosome to survive, and occasionally losing the only correctly inherited copy — which links UPD directly to the biology of miscarriage, chorionic villus mosaicism and apparently "unexplained" syndromes. ## What you must remember - **Two forms:** heterodisomy — both homologues from one parent (meiosis I nondisjunction, two different grandparental chromosomes); isodisomy — two copies of the same homologue (meiosis II error or post-zygotic duplication), which creates long stretches of homozygosity. - **Three routes of origin:** trisomy rescue (commonest), monosomy rescue (duplication of the lone chromosome), and gamete complementation (a disomic gamete meets a nullisomic gamete for the same chromosome). - **Imprinting disorders caused by UPD:** Prader-Willi from maternal UPD15 (about a quarter of Prader-Willi cases, the rest mostly deletions); Angelman from paternal UPD15 (a small fraction); Beckwith-Wiedemann from paternal UPD of 11p15 (roughly a fifth of cases); Russell-Silver from maternal UPD7 or 11p15. - **The isodisomy trap for recessive disease:** a child with cystic fibrosis, congenital adrenal hyperplasia or spinal muscular atrophy born to a family where only one parent is a carrier can have inherited two identical mutant copies through isodisomy; UPD thus mimics autosomal recessive inheritance with a single carrier parent. - **Robertsonian translocation link:** UPD of chromosomes 13, 14 and 15 can follow trisomy rescue in Robertsonian translocation carriers — a counselling connection between the two topics. - **Detection:** methylation-specific studies (MS-MLPA) reveal the parent-of-origin pattern; single nucleotide polymorphism microarrays show long contiguous stretches of absence of heterozygosity flagging isodisomy; standard karyotype is normal — a point examiners emphasise. - **Recurrence risk:** nearly always low when UPD arises sporadically after trisomy rescue, but parental translocation or mosaic UPD mandates individualised counselling. ## Trisomy rescue, step by step Walk the mechanism because every UPD fact hangs on it. Step one: maternal meiosis I nondisjunction produces an ovum with two maternal chromosome 15s; fertilisation adds the paternal copy — a trisomic conception that would miscarry. Step two: an early mitotic division ejects one of the three chromosomes at random; the embryo survives as a disomy. Step three: the gamble — one third of the time the cell discards the paternal copy, leaving two maternal copies, maternal UPD15; with imprinted, paternally expressed genes (the SNRPN cluster) silent on both copies, the baby has Prader-Willi syndrome despite a normal chromosome count. The same rescue explains laboratory phenomena: a chorionic villus sample showing trisomy 15 mosaic in the placenta with a euploid fetus implies rescue occurred, and the fetus must then be checked for UPD. This chain — nondisjunction, trisomic conception, rescue, UPD — is the examinable sequence, and it converts imprinting from a memorised word into a mechanism. ## Where the exam sets its traps The deletion-negative Prader-Willi case is the classic trap: fluorescence in situ hybridisation for the 15q deletion is normal, and candidates stop; the answer is that maternal UPD and imprinting defects account for the deletion-negative majority, so methylation analysis — not repeated FISH — is the next test. Second, candidates forget that UPD requires the parent-of-origin to be wrong, not the gene sequence: the chromosomes may be entirely normal in sequence and dosage. Third, the isodisomy mechanism for recessive disease is under-quoted: a "one-carrier-parent" child with an autosomal recessive phenotype should prompt microarray analysis for homozygosity — elegant reasoning that distinguishes a postgraduate answer. Finally, do not promise recurrence risk of zero; trisomy rescue is sporadic, but maternal age and translocation contexts modify the counselling. ## Frequently asked questions ### What is the difference between heterodisomy and isodisomy? Heterodisomy inherits both different homologues from one parent (meiosis I error), while isodisomy duplicates a single homologue, making the carrier homozygous across that region. ### How does trisomy rescue generate uniparental disomy? A trisomic conception loses one chromosome to survive; if the sole copy from the other parent is the one discarded, the remaining pair is uniparental. ### Which syndrome results from maternal UPD of chromosome 15? Prader-Willi syndrome, because the paternally expressed genes are silenced on both maternal copies — it is the commonest cause of deletion-negative Prader-Willi. ### How can a child show autosomal recessive disease with only one carrier parent? Isodisomy transmits two identical copies of the carrier parent's mutant allele, effectively making the child homozygous. ### Which test detects uniparental disomy when the karyotype is normal? Methylation-specific analysis such as MS-MLPA for imprinting disorders, and SNP microarray demonstrating absence of heterozygosity for isodisomy.