Mosaicism in rare disease

Abstract Mosaicism is the presence of two or more genomes in an individual derived from a single zygote. Mosaicism may occur in germ cells (germline mosaicism), potentially causing recurrent aneuploidies in offspring. It may also occur in somatic cells as a postzygotic event. The mosaic events may involve small regions (single nucleotide variants or insertions/deletions) or large chromosomal regions including aneuploidy. Mosaicism may also occur in selected cells across the body or it may be confined to a particular organ or region. Recent next-generation sequencing methods have improved the sensitivity to detect mosaic events, elucidating their roles in a broad range of diseases including aneuploidies, obligate mosaic diseases that are otherwise lethal in the germline, and Mendelian diseases that manifest in a mosaic form.