Uniparental disomy, isodisomy, and imprinting: probable effects in man and strategies for their detection.

The concept of uniparental disomy--the presence of a chromosome pair derived solely from one parent in a diploid offspring--was introduced in 1980 as a probable consequence of the high rate of germ cell aneuploidy in man, and has now been convincingly demonstrated through molecular analyses in several families. A most likely mechanism for the production of uniparental disomy is the chance reunion, and complementation, of 2 gametes aneuploid for the same chromosome member; uniparental disomy could also occur through other mechanisms including postzygotic non-segregation in a trisomic conceptus. Uniparental disomy may result in isodisomy, i.e., homozygosity of a series of contiguous alleles in a pair of homologues. The presence and degree of isodisomy in an offspring depend in turn on the occurrence, timing, and extent of the meiotic recombination that had occurred in the chromosome pair of the disomic gamete involved. Uniparental disomy with or without isodisomy can explain a number of unusual observations, such as the unexpected pattern of transmission of a genetic disorder. The two may be associated with an imprinting effect to produce pathological phenotypes, as has been observed in the mouse, and may be the basis for a number of syndromes of as yet unclear cause. The evidence for uniparental disomy, isodisomy, and imprinting in man is reviewed, and strategies for their detection presented.