Cytogenetics 1/2/3/ and cancer cyto Flashcards
substance during preparation for cytogenetics
added to promote cell division
PHA
Phytohemaglutinin
female meiosis begins
3rd month of gestation
phase of female meiosis , right before birth
until puberty
Prophase I (dictyotene)
phase of female meiosis
after ovulation
Metaphase II
Female meiosis is completed
after
Fertilization
When is the 1st polar body of female meiosis formed
Before metaphase II
any abnormality that is not a multiple of 23
Aneuploidy
what are two main mechanisms of aneuploidy
- Non-disjunction
- Anaphase lag
Most triplodies originate during oogenesis except for ____ which is equally likly to arise during oogenesis or spermatogenesis
XXY
trisomy most likly to be a meiosis II error
trisomy 18
however most trisomies are M1 errors
monosomy X is more likly to be _______ in origin
paternal (70%)
maternal (30%)
male nondisjunction in meiosis II most likly to form this aneuploidy
XYY
Percentage of Down syndrome that is Robersonian translocations and recurrance risk?
- Father
- Mother
- t(21;21)
4% Robersonian translocations (usually 14:21)
- Father with t(14;21) - 1%
- Mother with t(14;21)- 10-15%
- Etheir parent with t(21;21) - 100
developmental delay
high hairline
diaphragmatic hernia
seizures
sparse hair, large mouth
normal karyotype
tetrasomy 12p
Pallister-Killian
Isochromosome 12p
tissue specific mosaicism
must do skin biopsy or microarray
generally the tissue from which CVS karyotype is obtained
Inner mesenchymal core
Most common autosomal trisomy associated with spontaneous abortions
Trisomy 16 (30%)
followed by 22 and 21
single most common chromosomal abnormality in spontaneous abortions
monosomy X
Risk associated with complete molar pregnancies
46 XX (90%)
Malignancy (Choriocarcinoma)
1-2% risk of recurrance
number of barr bodies found in a XXY male
1 barr body
of barr bodies = number of X chromosomes -1
chromosomal location of XIST/XIC
Xq13
what is the product of XIST
produces a non-coding RNA
that coats the inactive X to inactivate it
percentatge of genes that usually excape inactivation on X chromsome
10-15% total
30% on short arm Xp
3% on the long arm Xq
**Multiple copies of short arm more likly to produce an abnormal phenotype than multiples of the long arm
which turner syndrome karyotype would be expected to have a more severe phenotype
46,X,r(X) - large ring
46,X,r(X) - small ring
46,X,r(X)
small ring less likly to contain XIST
therefore functional disomy of portions of X chromosomes
genes that are usually inactivated
Most common robersonian translocation
t (13;14)
draw germ cells that can be formed from a 45,XY,t (13;14)
Alternate
Adjacent
3:1
how do you determine whether an unbalanced translocation underwent adjacent 1 or adjacent 2 during gamate formation
Adjacent 1
each pole gets a normal chromosome and the opposite translocated chromosome
partial monosomies and trisomies
Adjacent 2
each pole gets both the normal and translocated of the same chromosome
rare
for duplication ________analysis is preferred for visualization of tandem duplications
for deletions ________ is prefered
interphase
metaphase
prenatal aneuploid screen
probes target the centromeres of ___,___,___
cetromeric probes are not specific to ___,___ so must use locus specific probes
18,X,Y,
13,21
___ ___ FISH strategy used for loci which rearrange with multiple partners
“break apart”
FISH probe cocktail for detection of del 22q11.2
22q11.2 LSI TUPLE 1
22q13 LSI ARSA
Philidelphia chromosome
der (22)
CML- tramslocation 9;22
beakpoint on chromosome 9 is constant
creation of more chromosomal abnormalities in a tumor
clonal evolution
BCR-ABL found using _________ probe
dual-fusion
treatment used for myelodysplasitic syndrome
PML/RARA
t(15;17)
ATRA (all-trans retinoic acid)
progressive ataxia
oculocutaneous telangiectasia
immune deficiency
chromosome instability when exposed to xray
increased AFP
Ataxia telangiectasia
ATM (loss of function mutation)
can have positive newborn screen for TREC (immune deficiency)
butterfly rash
growth deficiency
immune defects
increase sister chromatid exchange
Bloom Syndrome
BLM
RecQ helicase
cardiac, renal, limb anomalies
progressive bone marrow failure
radial ray anomalies
“VACTRL”
increase chromosome breakage
Fanconi Anaemia
- FANC-A* (60-70%)
- FANC-C* : most common in AJ pop.
testing of lymphocytes with diepoxybutane (DEB) and mitomycin C (MMC)
BRCA1 and BRCA2 are part of the FANC pathway
