Isodisomy is a form of uniparental disomy (UPD) in which an individual inherits two identical copies of a chromosome, or a segment of a chromosome, from a single parent, with no genetic contribution from the other parent for that chromosome. It differs from heterodisomy, in which a pair of non-identical homologous chromosomes (i.e., both members of a homologous pair) are inherited from one parent, typically resulting from a meiosis I error. In isodisomy, the fertilized ovum contains two identical copies of a single parental chromosome, usually arising from a meiosis II error or from post-fertilization duplication of a single parental chromosome.
Mechanism
Isodisomy can occur through several mechanisms:
- Meiosis II nondisjunction: A single parental chromosome fails to separate during the second meiotic division, producing a gamete with two identical copies of that chromosome.
- Post-fertilization duplication: A chromosome from one parent is lost and the remaining copy from the other parent is duplicated (monosomy rescue).
- Compensatory isodisomy: A trisomic zygote loses one chromosome, leaving two copies from the same parent.
Clinical Significance
Because the two copies are identical, isodisomy results in complete homozygosity across the entire chromosome or chromosomal segment. This can lead to the expression of recessive genetic disorders if the inherited chromosome carries a deleterious recessive allele that would otherwise be masked by a normal allele from the other parent. Isodisomy is also a mechanism for loss of heterozygosity (LOH) in certain cancers, such as glomuvenous malformations.
Additionally, isodisomy can disrupt genomic imprinting—the phenomenon where certain genes are expressed in a parent-of-origin-specific manner—potentially leading to growth abnormalities or developmental disorders (e.g., Beckwith-Wiedemann syndrome, Prader-Willi syndrome, or Angelman syndrome, depending on the chromosome involved).
Diagnosis
Isodisomy is typically diagnosed through prenatal testing (e.g., amniocentesis) or through genetic analysis using techniques such as chromosomal microarray analysis, single-nucleotide polymorphism (SNP) arrays, or DNA methylation studies. It may be detected incidentally in a fetus or child without obvious abnormalities.
Prevalence
Isodisomy is considered rare, though some researchers suggest it may be a more common phenomenon in human cells than previously recognized and might play a role in the pathogenesis of various nonmalignant disorders, potentially explaining local impaired function and clinical variability.
