11/07 - The Problem of Mosaicism

Question 1

Mosaicism Definition

Answer 1

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

Question 2

Mosaic vs. Chimera

Answer 2

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

Question 3

As a result of Lyonization… Most females are _____________

Answer 3

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

Question 4

X-inactivation

Answer 4

• 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

Question 5

General features of chromosome mosaicism

Answer 5

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

Question 6

Mosaic Down Syndrome

Answer 6

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

Question 7

46,XX/47,XX,+13

Answer 7

• 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.

Question 8

Sex Chromosome Mosaicism

Answer 8

• 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

Question 9

Mosaicism for a structural abnormality

Answer 9

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

Question 10

Other types of mosaics

Answer 10

• Diploid/triploid mosaicism

- Diploid/tetraploid mosaicism

Question 11

Triploidy starts how?

Answer 11

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

Question 12

Rare, unusual cases

Answer 12

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

Question 13

Prenatal Diagnosis

Answer 13

• Mosaicism in amniotic fluid

- Mosaicism in CVS

Question 14

Three Major types of Mosaicism

Answer 14

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

Question 15

Types of placental-fetus mosaicism

Answer 15

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

Question 16

Confined placental mosaicism

Answer 16

• 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

Question 17

Four main types of mosaicism encountered

Answer 17

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

Question 18

Cancer is..

Answer 18

acquired somatic mosaicism

Question 19

Uniparental disomy (two mechanisms that can produce this)

Answer 19

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

Question 20

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

Answer 20

• 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

Question 21

Research and future

Answer 21

• Mouse tetraploid chimeras rescue lethal phenotype

- New ways to detect and estimate mosaicism - CGH

Question 22

UPD pathogenesis

Answer 22

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

Question 23

patUPD6

Answer 23

• clinically important

- Biallelic expression of maternally imprinted genes

Question 24

Important things to know for cultures and mosaicism

Answer 24

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