chromosomal abnormalities Flashcards
(25 cards)
how is the karyotype prepared?
- collect c.5ml heparinised venous blood
- isolate white cells
- culture in the presence of phytohemagglutinin to stimulate t-lymphocyte growth/differentiation
- add colchicine after 48 hours to cause cardiac arrest
- place in hypotonic saline
- place on a slide
- fix and stain
what is giemsa staining done for?
to leave a recognisable pattern of bands
what are the darker bands on a chromosome called
heterochromatin- more compact, fewer genes
what are the lighter bands on the chromosome called
euchromatin- more open, more genes
when is whole genome sequencing used?
for all cancer patients and as of sept 22, all children w suspected abnormality
what is aneuploidy?
an abnormal number of chromosomes
what is non-disjunction
mistake during meiosis which results in an uneven number of chromosomes- either +1 or -1 chromosome
when non-disjuncture occurs in meiosis 2 how many daughter cells are affected
half of them
most common form of chromosome aneuploidy?
sex chromosome- affects 1 in 400 males and 1 in 650 females
why is sex chromosome imbalance tolerated?
-x inactivation of excess X chromosomes so only 1 is active
- low gene content of Y chromosome
when does most trisomy 21 arise?
maternal non-disjunction
why does maternal non-disjunction increase with age?
vulnerability of oogenesis
- oogenesis is paused in utero in prophase 1 until puberty
- secondary oocyte arrests in metaphase II
- this only completes if fertilised
- one primary oocyte yields only 1ovum
- there’s a finite number of primary oocytes
most likely due to degradation of factors which hold homologous chromatids together
single gene disorders affected by paternal age effect
apert syndrome
crouton syndrome
pfeiffer syndrome
what’s the risk of a still birth, the risk of spontaneous abortions with aneuploidy?
5% still births, 50% spontaneous abortions
what is mosaicism?
the presence of 2 or more populations of cells with different genotypes
how can mosaicism arise?
-non-disjunctyre during early development
-loss of extra chromosome in early development
what is the phenotypic effect of mosaicism?
it results in a milder phenotype generally
most common mosaic?
46,XX/45,X
46,XY/45,X
types of single chromosome abnormalities?
deletion- may be the result of unequal crossover, can occur at ends or cause breaks in chromosome
duplication- usually caused by unequal crossover
paracentric inversion- carriers unaffected, estimated 1 in 1000, can cause reproductive problems or children with deletions/ insertions
types of two chromosome abnormalities
insertion
translocation (swapsies)
characteristics of Williams syndrome?
7q11.23 deletion
long philtrum
upturned nose
arched eyebrows
super vascular aortic stenosis
friendly, social personality
how is William’s syndrome detected?
using FISH- fluorescent in situ hybridisation
lack of elastin on affected chromosome
characteristics of duplication syndrome
delayed speech development
ASD like behaviour which affect social interaction and communication
dilatation of the aorta
flat eyebrows
broad nose, short philtrum
characteristics of robertsonian translocation
1 in 1000 ppl
occurs between Afrocentric chromosomes]may be homologous or non homologous
most common are 14 and 14, 14 and 15, 14 and 21
most people show no effects but can cause problems in offspring
