Figure 2.

Occurrence of somatic mosaicism across embryonic and fetal development, including development from the morula (16-cell stage) and blastocyst. The embryo forms from the inner cell mass of the blastocyst, while the placenta develops from the outer cell mass (from the trophoblasts at the exterior of the blastocyst). Mutations are indicated with a lightning bolt symbol, (a) Euploid (wild type) development. A normal karyotype (46,XX for a female in this example) is indicated, (b Germline mosaicism. Mutation can occur in the germline (e.g., germ cell precursors) of an embryo. Mosaic mutation is limited to germ cells that may later be transmitted to offspring as inherited germline variations. The individual depicted here, harboring the germ cell mosaic, may eventually become a parent who is phenotypieally normal, (c) Postzygotic mosaic mutations. Whether involving aneuploidy (whole chromosome gains or losses) or single nucleotide variants, postzygotic mosaic mutations can manifest through the entire body of an individual, particularly if the mutation occurs early in development, or be constrained to particular regions or organs, as indicated here. Trisomies that are ordinarily lethal (trisomies 1–12, 14–17, 19–20, and 22) may persist in the mosaic state with variable clinical phenotypes, (d) Confined placental mosaicism. Mosaic mutations can occur solely in the placenta while the fetus has a normal karyotype. A postzygotic, somatic mutation may lead to a cell and its daughter cells having mosaicism (such as mos 46,XX/47,XX+21 for mosaic trisomy 21) in a subset of the placental cells. Chorionic villus sampling can indicate trisomy 21. Determining whether the fetus is euploid or trisomic requires a separate test, such as amniocentesis, (e) Uniparental disomy. A trisomy (such as 47,XX+15) can arise at an early embryonic stage, persisting as a mosaic in the placenta (mos 46,XX/47,XX+15). In the embryo, trisomic rescue may occur in which a third copy of the chromosome is deleted from the cell. Rescue produces disomy and a euploid state (46,XX) or disomy in which both copies of the chromosome derive from one parent [e.g., maternal uniparental disomy (UPD mat)]. Uniparental heterodisomy refers to a meiosis I error, and both copies of the chromosome are from one parent but from different homologs. Uniparental isodisomy results from a meiosis II error or occurs through postzygotic duplication (as shown here). In this example, the child is susceptible to developing Prader-Willi syndrome [Online Mendelian Inheritance in Man (OMIM) 176270], an imprinting disorder due to loss of the paternal copy of chromosome 15q11.2–q13. This figure was derived in part from a public domain image from the Human Placenta Project (https://www.nichd.nih.gov/sites/default/files/inline-images/HPP-placental-development.png) at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health).