11/07 - The Problem of Mosaicism Flashcards Preview

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1

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

2

Mosaic vs. Chimera

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

3

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

4

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

5

General features of chromosome mosaicism

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

6

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

7

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.

8

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

9

Mosaicism for a structural abnormality

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

10

Other types of mosaics

- Diploid/triploid mosaicism
- Diploid/tetraploid mosaicism

11

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.

12

Rare, unusual cases

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

13

Prenatal Diagnosis

- Mosaicism in amniotic fluid
- Mosaicism in CVS

14

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)

15

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)

16

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

17

Four main types of mosaicism encountered

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

18

Cancer is..

acquired somatic mosaicism

19

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

20

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

21

Research and future

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

22

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

23

patUPD6

- clinically important
- Biallelic expression of maternally imprinted genes

24

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.