Browse the corpus

Genetic mosaicism is defined as the presence of two or more cell lineages with different genotypes arising from a single zygote in a single individual. In contrast, if distinct cell lines derived from different zygotes, the term is now known as chimerism. Genetic mosaicism is a postzygotic mutation.[1][2] Since an adult human being requires countless cell divisions for its development (approximately 10 to the 16th power or, virtually, 10,000,000,000,000,000 mitoses) and every cell division carries a risk for genetic mistakes, each person has at least one genotypically distinct cell in their body; thus every individual is a mosaic. Also, probably all the cells within every single human being encompass numerous mutations that could potentially explain every human genetic disease. Nonetheless, only a minimum of these mutational events affects the individual’s well-being, while most are phenotypically silent (i.e., mutations are not relevant for cell function, mutant cells are eliminated by apoptosis). Mosaicism appears to be responsible for an enormous amount of pathologies, ranging from chromosomal abnormalities, such as Turner syndrome, to a myriad of cancers. Both benign and malignant tumors constitute evidence of somatic mosaicism in the human body.[3][4][5][6]

Mutation at the gene and/or chromosomal level may lead to chromosomal instability leading to cells with different genotypes. Mosaic chromosomal aberrations lead to abnormal phenotypes that also include irregular or altered production of protein.[53] The altered phenotype of a group of cells is expressed as clinical manifestation also; which can be understood by the following examples. A somatic chromosomal aberration has a role in production amyloid precursor protein that may affect neurodegenerative diseases like Alzheimer's disease.[54] In trisomy 21 down syndrome, a significant difference has been found in Intelligent Quotient between-group without mosaicism and a group with mosaicism [individuals have both trisomic (47, XX,+21 or 47, XY,+21) and euploid (46, XX or 46, XY) cell lines].[55] In patients with Turner syndrome with mosaicism, the loss of the X chromosome may have happened during cell division of early embryonic stages. That results in some cells have only one copy of the X chromosome (45, 21+X0), and some cells have two copies of X chromosomes (46, 21 + XX). The mosaic individual has less severity of symptoms.[56] In brief, a cascade can be described as following in somatic mosaicism.[57][58][59][3][60][61][11] An altered genome during mitosis or meiosis Cells with two or more types of genotypes The function of the cell is affected e.g., secretion of the protein, production of the hormone, etc. (e.g., Decreased production of testosterone in Klinefelter syndrome). Depending on the population of the affected cells, the tissue function may also deteriorate (the more cells with mutated genome the more the function is affected. The hormonal effect on organs in Turner syndrome, demyelinated cells in neurodegenerative diseases). Expression as clinical symptoms (e.g., Low intelligent quotients in turner syndrome, dementia in Alzheimer disease, gynecomastia in Klinefelter syndrome) In some cases, mutated cells may proliferate because of the triggering factor and lead to malignant condition also (e.g., somatic genomic mosaicism in multiple myeloma, ovarian carcinoma) For germline cell mosaicism:[62][63][64][11][65] The germ cells mutate during meiosis (e.g., some sperms with 22, X0, some sperms with 24, XXY). The affected person does not show any symptoms, but it passes to the offspring.

In some cases, mutated cells may proliferate because of the triggering factor and lead to malignant condition also (e.g., somatic genomic mosaicism in multiple myeloma, ovarian carcinoma) For germline cell mosaicism:[62][63][64][11][65] The germ cells mutate during meiosis (e.g., some sperms with 22, X0, some sperms with 24, XXY). The affected person does not show any symptoms, but it passes to the offspring. Affected germ cells fuse with normal/abnormal germ cells (e.g., sperm with 22, X0 fuses with oocyte with 23, XX) forms with two lineages of somatic cells (45, X0 and 46, XX) Now on the base of the population of the abnormal somatic cells, the offspring expresses phenotypes as it does in somatic mosaicism.