From the Guidelines
Mosaicism is a condition characterized by the presence of two or more populations of cells with distinct genetic makeup within an individual, resulting from mutations or chromosomal abnormalities that occur post-zygotically 1.
Key Characteristics of Mosaicism
- This phenomenon can affect any cell type, including somatic, germ, or a combination of both, and may be detected through various diagnostic techniques, such as fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) 1.
- The clinical significance of mosaicism depends on the type and proportion of affected cells, as well as the specific genetic alteration involved, and may be associated with a range of disorders, including cancer, neurodevelopmental disorders, and congenital anomalies 1.
Detection and Diagnosis of Mosaicism
- Low-level mosaicism for unbalanced rearrangements and aneuploidy may not be detected by microarray analysis, and the level of detectable mosaicism will vary by size, region of genome, copy number state, DNA quality, and data quality 1.
- Fluorescence in situ hybridization (FISH) analysis of fresh (uncultured) samples provides a reliable means to establish the level(s) of mosaicism detectable by microarray, and conventional cytogenetic analysis of metaphase cells provides information about mosaicism but may not accurately reflect levels of mosaicism 1.
Clinical Significance of Mosaicism
- Mosaicism can have significant clinical implications, particularly in the context of genetic disorders and cancer, where the presence of mosaic cells can influence disease progression and treatment outcomes 1.
- The detection and characterization of mosaicism are crucial for genetic counseling and prenatal diagnosis, as well as for the development of personalized medicine approaches 1.
From the Research
Definition of Mosaicism
- Mosaicism is defined as the coexistence of cells with different genetic composition within an individual, caused by postzygotic somatic mutation 2.
- It denotes an individual who has at least two populations of cells with distinct genotypes that are derived from a single fertilized egg 3.
- Mosaicism describes the presence of two genotypically different cell lineages within the same organism, which can arise from small mutations or errors in chromosome segregation 4.
Types and Causes of Mosaicism
- Somatic mosaicism refers to the occurrence of two genetically distinct populations of cells within an individual, derived from a postzygotic mutation 5.
- Genetic variation among the cell lines can involve whole chromosomes, structural or copy-number variants, small or single-nucleotide variants, or epigenetic variants 3.
- Mosaicism can result from postzygotic alterations during embryogenesis, leading to genetically distinct populations of cells within individuals 6.
Characteristics and Effects of Mosaicism
- The mutational events that underlie mosaic variants occur during mitotic cell divisions after fertilization and zygote formation, leading to enormous variation in the distribution and phenotypic effect of mosaicism 3.
- The phenotypic consequences of somatic mosaicism are dependent upon many factors, including the developmental time at which the mutation occurs, the areas of the body that are affected, and the pathophysiological effect(s) of the mutation 5.
- Mosaicism can be directly responsible for many conditions that present in a wide range of tissues, with the presence of the mutation or genetic abnormality following a tissue-dependent pattern 4.