Uniparental disomy revisited: The first twelve years

Abstract

Uniparental disomy (UPD), the exceptional derivation of a pair of the offspring chromosomes from one parent only, may be compatible with normal or abnormal development and can result from gamete complementation, chromosome loss in trisomy, or duplication in monosomy, (with or without residual mosaicism) and somatic recombination. In isodisomy, the uniparental pair is a duplicate of a same chromosome DNA template and causes and increased risk or recessive disorder by reduction to homozygosity. In heterodisomy, the pair remains heterozygous, made up of 2 non‐recombinant homologous segments. But both iso‐ and heterodisomy may also cause disruption of the genomic imprints needed for differential expression of some maternal and paternal genes crucial to growth and development. Pure UPD preserves euploidy and, when harmful, is best regarded as a genomic qualitative imbalance by symmetrical excess and loss of parental homologous contribution affecting zygosity and imprint content. Instances of UPD reported till the spring 1992 are reviewed and their deleterious effects are described as they carried out lethality or morbidity by altering imprinting processes, mimicking deletions, generating recessive disorders, or prompting malignant cellular growth.