Mosaicism Flashcards
What is mosacism?
Person has two or more genetically different sets of cells
At what stage can mosaicism occur?
Can occur at any stage of development from the two-cell stage onwards
Occurs during mitotic division
What are the causes of mosaicism?
Unusual events in mitosis
Gene mutation during development (pre/post-zygotic mutation)
Chromosomal mutation during development
X-inactivation (one X chromosome is randomly switched off in cells of female mammals)
Numerical or structural abnormalities of chromosomes (Deletion/Aneuploidy)
What is chimerism?
Presence of two or more cell lines (genotypes) that are derived from different zygotes in an organism
Outline the differences between mosaics and chimeras
Conditions caused by mosaicism
Cancer
Heterochromia iridis
Lines of Blaschko
Neurofibromatosis type I
Proteus syndrome
Osteogenesis imperfecta type II
What are the types of mosaicism?
Somatic mosaicism
Germline mosaicism
Gonosomal mosaicism
Chromosomal mosaicism
Reversion mosaicism
What is somatic mosaicism?
Occurrence of two genetically distinct populations of cells within an individual, derived from a postzygotic mutation
Generally, this form of mutation is milder because it is confined to a region of the body
What are some examples of somatic mosaicism?
Cancer
Down syndrome
Lines of Blaschko
What are Lines of Blaschko
Represent pathways of epidermal cell migration and proliferation during the development of the fetus
These lines are invisible but many inherited and acquired diseases of skin manifest themselves according to these patterns creating the visual appearance of these lines
What is germline mosaicism?
Mutation of precursor diploid germ cells in the gonads
Mosaic germline mutations can be passed to offspring
Can occur with any inheritance pattern, but is commonly autosomal dominant and X-linked
Inidivual is unaware of mutation until their children are affected
What are some examples of germline mosaicism?
Osteogenesis imperfecta
Ovarian dysgenesis
What is osteogenesis imperfecta type II?
Defective connective tissue because of deficiency of Type-I collagen
Bones are brittle and prone to fracture (OI is also called brittle bone disease)
Eight variations of OI - mostly caused by mutation of COL1A1 and COL1A2 genes
Usually lethal in perinatal period - most cases die within the first year of life with respiratory failure or intracerebral haemorrhage
What is gonosomal mosaicism?
Type of mosaicism which occurs early in development affecting both somatic and germline cells
Example: Neurofibromatosis Type II (NF2)
Gonosomal mosaicism = Somatic mosaicism + Germline mosaicism
What is NF2?
Autosomal dominant cancer syndrome
Caused by mutations inactivating the NF2 tumor-suppressor gene in 22q12 - production of Merlin peptide is reduced (Merlin has tumor-suppressive functions)
Merlin’s deficiency can result in unmediated progression through the cell cycle causing tumors
Symptoms: Dizziness; headache; facial weakness, numbness, or pain; ringing in the ears; and progressive hearing loss.
What is proteus syndrome?
Condition causing overgrowth of skin, bones and other tissues
Caused by mutation of the AKT1 gene which regulates cell growth and proliferation and cell death
Allows the cell to grow and divide abnormally
