Uniparental disomy and genomic imprinting as causes of human genetic disease.

The existence of parent-of-origin differences in the expression of some genes, a process known as genomic imprinting, has been recognized and documented over the past several years. This epigenetic marking process results in the differential expression of normal genes depending upon whether they were inherited from the mother or the father. A number of human disorders have been identified as resulting from alterations in genomic imprinting. One process which can unmask genomic imprinting is uniparental disomy, in which both members of a chromosome pair are contributed by one sex parent. When uniparental disomy is present, genetic abnormality can result either from homozygosity of a single mutant allele which is present in two doses, or from the presence of two copies of an imprinted unexpressed gene or genes, rather than the usual one expressed and one unexpressed. Examples of human genetic disorders that are the consequence of genomic imprinting, and a discussion of current knowledge about the mechanisms of imprinting and the causes of uniparental disomy, are reviewed.