Mechanisms leading to uniparental disomy and their clinical consequences

Uniparental disomy (UPD) refers to the situation in which both copies of a chromosome pair have originated from one parent. In humans, it can result in clinical conditions by producing either homozygosity for recessive mutations or aberrant patterns of imprinting. Furthermore, UPD is frequently found in conjunction with mosaicism for a chromosomally abnormal cell line, which can also contribute to phenotypic abnormalities. Investigations into the mechanisms by which UPD may arise have helped to expand our general awareness of the impact of chromosomal abnormalities and chromosomal mosaicism in normal human development. Specifically, it appears that errors in the transmission of a chromosome from parent to gamete and during early somatic cell divisions are remarkably common but that embryo and cell selection during early embryogenesis help to ensure the presence of a numerically balanced chromosome complement in the developing fetus. UPD is also likely to occur within a portion of cells in all individuals simply as a consequence of somatic recombination occurring during mitotic cell divisions. This can be an important step in cancer development as well as a contributing factor to other late onset diseases. This review summarizes mechanisms by which UPD may arise and their associated clinical consequences.