Mosaicism and Chimerism

Question 1

Chromosomal mosaicism

Answer 1

Cells with different chromosomal complements in an individual
derived from one zygote

Question 2

Chimerism

Answer 2

Traditional definition: Cells with different haploid complements in an individual
derived from >1 zygote (i.e. tetragametic chimerism);

Question 3

Mixoploidy

Answer 3

mis-segregation of parental genomes results in chimera/mixed haploid
complement embryo (single egg chimerism)

Question 4

Sesquizygotic twins

Answer 4

Twins resulting from a mixoploid split, with unequal contributions to the two twins
sesqui = 1 and 1/2

Question 5

3 major types of chimerism:

Answer 5

Microchimerism
Embryo amalgamation
Mixoploidy - also referred to as whole- genome-mosaics or bi-gametic /tri-gametic chimerism
or “single –egg chimerism’

Question 6

Why is the true incidence (Mosaicism) underestimated?

Answer 6

chromosomal errors are extremely common in early embryos and these can have more severe downstream effects as multiple tissues can be affected. We do not know how often abnormal cells persist in development. What we do know is that in 1-2% of CVS samples there is a chromosome abnormality (usually a trisomy) that appears to be confined to the placenta and in 0.1% of amniocenteses there is a chromosomal mosaicism.

Question 7

How could you design a non-invasive blood test for cancer?

Answer 7

Just as cell-free placental DNA can be detected in maternal blood during pregnancy, cell free tumor DNA can also be detected in blood of some adults affected with certain tumors.

Question 8

Why is most trisomy mosaicism not diagnosed?

Answer 8

1. placental biopsies and amniocentesis sampling are the exception rather than the rule
2. even when it is, small pockets of abnormal cells can end up in single tissues, we can only speculate on what the potential role such undetected mosaicism may have on human disease.