Mosaicism in Humans

Abstract

The karyotype of most individuals is established at fertilization. In the great majority of cases, this constitutional karyotype is then maintained throughout subsequent somatic cell division. In a minority of cases, however, chromosomal errors and correction events in the early mitotic divisions post-fertilization can produce a pre-implantation embryo with two (or more) chromosomally distinct cell lines. If more than one cell line persists, the developing conception will then have a mosaic constitutional karyotype (mosaicism). Typically, this is one normal cell line alongside one abnormal cell line. Less frequently, more than one abnormal cell line may be present. Rarely, a normal cell line may not be apparent. Analysis of DNA polymorphisms will demonstrate that the various cell lines are derived from a single zygote, which distinguishes mosaicism from fusion events involving separate zygotes (chimerism), the latter being a much rarer condition in humans. The direct clinical consequences of mosaicism will depend on the relative proportions of normal and abnormal cells and how they become distributed during development of the fetus and the placenta, ranging from apparently benign low levels of abnormal cells restricted to the placenta through to high loads in the fetus producing significant congenital abnormality. Correction of trisomic conceptions can produce uniparental disomy which can have clinical consequences if imprinted or recessive genes are involved.