Isodisomy

Isodisomy is a type of uniparental disomy (UPD) in which an individual inherits two copies of a chromosome, or part of a chromosome, from one parent and no copy from the other parent, and both copies are identical. This means the individual has inherited two copies of exactly the same chromosome from one parent.

Isodisomy differs from heterodisomy, the other major type of UPD, in that heterodisomy involves the inheritance of two different chromosomes from one parent. In isodisomy, the two chromosomes are identical copies of each other.

The mechanism leading to isodisomy often involves an error in meiosis II, where sister chromatids fail to separate properly. This can lead to a gamete with two identical copies of a chromosome. After fertilization with a normal gamete from the other parent (containing no copy of that chromosome), the resulting zygote will have isodisomy for that specific chromosome. It can also arise through a post-zygotic error, such as a chromosome loss followed by duplication of the remaining chromosome.

The clinical significance of isodisomy arises primarily when the parent contributing the duplicated chromosome is a carrier for an autosomal recessive genetic disorder. Because both copies of the chromosome are identical, the child will inherit two copies of the recessive allele, resulting in manifestation of the disease. Isodisomy can also unmask imprinting disorders, if the chromosome is subject to genomic imprinting and the individual ends up with two copies of the chromosome imprinted in the same way. Additionally, the absence of heterozygosity (because both chromosomes are identical) across a region of the genome can raise concerns about increased risk of certain cancers and complex traits.