Mosaicism – where only some of an individual’s cells have a specific variant – can arise during embryonic development or after birth. Rarely, mosaicism can occur when a variant arises in a germ cell precursor, meaning the variant may, or may not, be passed on to offspring.
Mosaicism describes the situation where only a subset of the body’s tissues – either somatic or constitutional (germline) – carry a particular variant.
- Somatic mosaicism can derive from a variant that occurs during embryonic development (see figure 1), giving rise to an individual with some tissues that have a variant and some that do not.
- The variant can ultimately be present in large numbers of cells in the body, and these can result in a wide range of presentations, even with the same DNA alteration. This is primarily down to which parts of the body the affected cells eventually give rise to. The earlier in development a change occurs, the more parts of the body are likely to be affected.
- In the case of variants in genes that cause genetic disorders, somatic mosaicism may lead to a milder or atypical form of the condition.
Figure 1: Errors during embryonic development
- Somatic mosaicism can also arise after birth. In these cases, the variant will only be present in a localised area (see figure 2).
- For example, most cancers are the result of changes to DNA occurring later in life, which initially only affect a few cells in a particular region that then go on to proliferate.
Figure 2: Errors following birth
Constitutional (germline) mosaicism
- Constitutional (germline) mosaicism is a rare phenomenon that occurs when a variant arises in a germ cell precursor and is therefore present in only a subset of an individual’s sperm or egg cells.
- In this circumstance, a variant may or may not be passed on to any given offspring, depending on whether it is present in the particular germ cell that forms the embryo or not.
- Germline mosaicism can underlie the very rare recurrence of a previously presumed de novo dominant genetic condition in a subsequent offspring when neither parent is found to carry a constitutional (germline) variant.
- HEE Genomics Education Programme: Genomics 101: Inheriting Genomic Information
- NHS England: National Genomic Test Directory and eligibility criteria