11/07 - The Problem of Mosaicism Flashcards
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
X-inactivation
- 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
46,XX/47,XX,+13
- 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
patUPD6
- 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.
