chromo abronmal Flashcards
how to Prepare karyotype
collect peripheral blood Isolate white cells Culture in presence of phytohaemagglutinin Stimulates T-lymphocyte growth/differentiation After 48 hours add colchicine Causes mitotic arrest – metaphase Place in hypotonic saline Place on slide Fix and stain
dna is compacted around
histones futher condesed to Chromatin
common chromosome features
telomere at both ends centromere between both arms p-arm (short – petite) q-arm (long arm) light and dark bands
what stain causes the bands
Giemsa staining leaves a recognizable pattern of bands
can detect major chromosome abnormality
what causes bands
Bands caused by differently staining
how is increase in resalution measured
more bphs – bands per haploid set
what are the darker areas
Dark (heterochromatin) more compact fewer genes
light area
Light (euchromatin) more open more genes
what phase are is karotype done
and why
Now often done prophase rather than metaphase
as the chromosomes are less compact so more detail
another form of stain for karyotype
Karyotype fluorescent stain
can identify some forms of chromosmes abnormaility
what is Aneuploidy
abnormal number of chromosomes
n
what is meiosis and what is the function
production of gametes
To achieve reduction from diploid (2n=46) to haploid (n=23)
To ensure genetic variation in the gametes
how does it ensure To ensure genetic variation in the gametes
Enables random assortment of homologues and recombination
what is Non-disjunction
Non-disjuncture results in uneven number of chromosomes in daughter cells.
when does it happen
occurs in meiosis 1 or 2
what is results in
Always results in either +1 or -1 chromosome
When fertilized either trisomy or monosomy
diff between m1 and m2
Meiosis I all daughter cells affected
or half in m2
Why is s chromosome imbalance tolerated?
most common form og aneiploidy
X-inactivation of excess X chromosomes
Only one X-chromosome active
Low gene content of Y chromosome
Why if inactivated does abnormal number X have effect
Both X and Y chromosome have PAR
PAR- pseudo-autosomal region
x chromosme par
not inactived still produce genes
Trisomy 21/down syndrome how
Most trisomy 21 arises in maternal non-disjunction
during maternal meioisis
down syndrome vs age
Risk of maternal non-disjunction increases with age
higher chance of having baby with ds
Why is there a maternal age effect
Paused in utero in prophase I until puberty Secondary oocyte arrests in metaphase II Only competes if fertilized One primary oocyte yields only one ovum Finite number of primary oocytes
what is oogenesis
Female non-disjunction
why
Likely due to degradation of factors which hold homologous chromatids together
Paternal Age Effect
Paternal Age not risk factor increased aneuploidy
Does affect a subset of single gene disorders
Paternal role in aneuplody
Although no age effect some aneuploidy paternal
smoking a risk factor (not maternal)
are aneuploidy captable with life
Most not compatible with life
s chromosome an exception
when does cross over chromosome happen
Occurs in prophase I
why
increases genetic diversity
how
Pairs of chromosomes align
Chiasma form and crossover occurs
can it go wrong
yes
Unequal crossover
chromosome aligned incorrectly
results in
duplication/extra meterial in one chromosome and deletion in another chromosome
Single chromosome abnormalities
deletion
duplication
pancreatic inversion
what is deletion
Can be the result of unequal cross over
Breaks in chromosome
Can occur at ends
what is duplication
Most often caused by unequal cross over
pancreatic inversion
where happen
can happen around the centromere or in the middle
are carriers effected
no
cause
Can cause reproductive problems
Children with deletions/insertions
Two chromosome abnormalities
transfer between non homolougous pair of chromosomes
if uni directional transfer
insertion
what is mutual exhange
swapped
if balanced
does not affect carrier may cause problems in off spring
what can it cause
can cause partial trisomy or monosomy
can it occur in somatic cells
Can occur in Somatic cells cf Philadelphia chromosome t(9;22)(q34;q11) CML
Williams syndrome what type of mutation
deletion
7q11.23 deletion
what facial changes
Short, upturned nose
Arched eyebrows
social changes
Friendly, social ‘cocktail party’ personality – an absence of social anxiety
can you detect it using karyotyping
no too small
what to use instead
Can be detected using targeted FISH
what cab you see
Lack of elastin on affected chromosome
7q11.23 duplication syndrome
causes what facualy
Flat eyebrows
Broad nose and short philtrum
social causes
Delayed speech development
Autistic behaviours that affect social interaction and communication
what has a milder phenotype out of deletion and duplication
duplication
what is meacentric
when the short and long arm are nearly the same length
… centromere roughly in the centre
submetacentric
short arm considerbly shorter than long arm
acrocentric
short arm reduced down to a vistigle stump
what are the acrocentric chromosoems in humans
13 14 15 21 22
why are they special
they can undergo Robertsonian translocation
you form normal and deritive chromosome
what can it cause
Can cause problems in offspring most people are unaffected causes unbalanced chromosome causing down syndrom on c21 or lethal
Mosaicism
Presence of two or more populations of cells with different genotypes
example.
X-inactivation results in mosaic expression
Mosaicism can arise two mechanisms
Non disjuncture during early development
Loss of extra chromosome in early development
