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Mosaicism Definition

- Condition where an individual has two or more genetically distinct cell lines derived from a single zygote, but differing because of mutation or nondisjunction


Mosaic vs. Chimera

In mosaics, the genetically different cell types all arise from a single zygote, wheras chimeras originate from more than one zygote


As a result of Lyonization... Most females are _____________

mosaics for the X chromosome and their cells are functionally hemizygous for one or the other X chromosome



- Female cats, with two X chromosomes, can have any of three genotypes relative to the orange gene: OO (orange coat), oo (black coat), or Oo (tortoiseshell or calico). The tortoiseshell pattern of fine patches of black and orange reflects the pattern of X chromosome inactivation in the hair follicles.
- Males have orange or black coat because they have only one X chromosome


General features of chromosome mosaicism

- Areas of hypo and hyper pigmentation
- Facial and body asymmetry
- Hypomelanosis of Ito


Mosaic Down Syndrome

- 2-3% of Down Syndrome individuals are mosaic
- In GENERAL, mosaic individuals have a milder phenotype
- Long term on going study in Virginia



- This conception may have started as a trisomic zygote and then lost one chromosome #13 from a somatic cell during development or
- It started as a 46,XX zygote and then a somatic cell became trisomic, giving rise to a mosaic condition.


Sex Chromosome Mosaicism

- 45,X/46,XX: can be seen: in an infant, in an adult-low level, in an adult-high level
- 45,X/46,XY: risk of gonadoblastoma


Mosaicism for a structural abnormality

- Marker chromosome
- Ring chromosome (has been observed for every chromosome) = unstable
- Dicentric chromosome = unstable
- deletion
- translocation


Other types of mosaics

- Diploid/triploid mosaicism
- Diploid/tetraploid mosaicism


Triploidy starts how?

STARTS as triploid and then cam give rise to diploid later on.. but you can't start out diploid and go triploid.


Rare, unusual cases

- Tissue limited mosaicism
- Pallister Killian Syndrome: iso12p extra piece of chromosome
- Germ line mosaicism


Prenatal Diagnosis

- Mosaicism in amniotic fluid
- Mosaicism in CVS


Three Major types of Mosaicism

- Global or generalized constitutional mosaicism
- Confined or tissue specific mosaicism
- Pseudomosaicism (won't see it in two different cell cultures)


Types of placental-fetus mosaicism

1) both mosaic (generalized)
2) confined placental mosaicism
3) placenta is normal and fetus is mosaic (doesn't happen often)


Confined placental mosaicism

- Trisomy 13,18,21
- Trisomy 7,8,9,10,15,16,22, and others
- Uniparental disomy: imprinted genes, trisomy effect, recessive genes, confined placental mosaicism is found in 1-2% of pregnancies studied by CVS


Four main types of mosaicism encountered

- Single cell mosaicism (Level I)
- Pseudomosaicism (Level II)
- Confined placental mosaicism (CPM)
- True mosaicism (Level III)


Cancer is..

acquired somatic mosaicism


Uniparental disomy (two mechanisms that can produce this)

1) Parental nondisjunction produces a sperm cell with two copies of a specific chromosome and maternal nondisjunction produces an ovum with no copies of the same chromosome
2) Nondisjunction (in the mother, in this example) results in a trisomic zygote


Chimeras are also produced experimentally, and have been a valuable research tool in several biomedical disciplines

- The basic technique is to combine two very early embryos such that their cells intermix and the resulting conceptus has cells from both original embryos
- It may be possible to extend this procedure to allow embryos from severely endangered species to be carried by recipient mothers from another species


Research and future

- Mouse tetraploid chimeras rescue lethal phenotype
- New ways to detect and estimate mosaicism - CGH


UPD pathogenesis

- Trisomy rescue to randome elimination of the normally inherited chromosome
- Monosomy followed by chromosome duplication
- Complementation between disomic and nullisomic gametes during fertilization



- clinically important
- Biallelic expression of maternally imprinted genes


Important things to know for cultures and mosaicism

- We keep at least 2 primary cultures for DNA extraction in case we need to confirm mosaicism.