Chromosome Abnormalities Flashcards
How many chromosomes do we have
22 autosome pairs
two sex chromosomes
46 total
What is the function of the centromere and what is it made of?
Joins sister chromatids
comprises of 100’s of Kilobases of repetitive DNA (constutive heterochromatin)
What are the two chromosomes arms called and what is at the end of the chromosomes?
p (petite) small arm
q = large arm
Telomeres that act as a cap (repeating non coding DNA)
protects genes from enzymatic attack
What are the light and dark bands?
Light bands are gene rich and contain less dense chromatin
Dark bands less gene rich, densely packed chromatin
How is a karytoype made?
cell sample taken
cells grown in tissue culture treated with phytohemagluttinin that triggers mitosis
colchicine is then added to prevent spindle fibre formation and halt mitosis (stuck in M phase)
cells paced in salt hypotonic solution –> water moves into cell they swell chromosomes separate more
Sainted with giemsa
arranged using light microscopy according to size and banding pattern into homologous pairs to produce a karyotype
Advantages and Disadvantages of Karyotypes
allows you to easily see that the number of chromosomes present is correct and any major translocations or deletions insertions that may have occurred
Disadvantage
cannot see individual genes and is not very detailed
is time consuming and expensive
What is FISH?
How does it work?
Why is it used?
Fluorescent in situ hybridisation
uses fluorescent probes to bind to chromosomes at a high degree of sequence similarity
used to identify translocations and whether particular sequences are present or absent due to deletions or insertions
has a much higher resolution. than a karyotype and identifies chromosomes with certainty
What is array CGH?
How does it work?
Advantages of this method?
array comparative gene hybridisation
Patients DNA is fixed onto a glass slide and then fluorescently labelled one colour (green)
normal reference DNA is placed on same slide and labelled with another colour (red)
Compete with specific hybridised probes
if equal amount of chromosome are present then the slide will be yellow
if they are parts of chromosomes missing the slide will be red
if there are extra parts of chromosome they will be green
most commonly use
greater resolution allows you to detect all changes in small sections of a chromosome
What are the two types of chromosomal abnormality
Numerical abnormalities:
Aneuploidy trisomy (3) or monosomy (1)
Polyploidy increase in overall chromosome no e.g 69 Triploidy
Structural chromosome abnormalities: translocations deletions duplications inversions
How would you write the chromosomes of a normal male
46, XY
What is 47, XX, +21
A female with Downs Syndrome
How would you write a female with Tuners syndrome
45, X
What is Downs syndrome
trisomy in chromosome 21
Edwards syndrome
Trisomy chromosome 18
Patau syndrome
Trisomy chromosome 13
What is Turners syndrome?
Symptoms?
females only have one X chromosome
results in short stature infertility delayed onset no onset of secondary sex characteristics
What is Kleinfelters syndrome?
Males have an extra X chromosome
Results in
issues with fertility delayed puberty development of poor secondary sex characteristics
Why are trisomies a problem?
Why don’t any other trisomies occur and why don’t you get people with monosomies?
results in gene dosage problem there are too many gene products leading to significant developmental issues
All other trisomies are incompatible for life
All monosomies are incompatible for life
effects of reducing gene copy more severe than increasing it
Down Syndrome incidence & clinical sings
1 in 700 live births
single palmar crease
small ears and mouth upward slanting nose and eyes
delayed development and metal handicap
white sports on iris
What are the possible causes of Down Syndrome
Trisomy in chromosome 21 (95%)
4% due to a Robertsonian translocation that results in trisomy
1% have mosaicism one normal cell line and one Downs cell line usually have milder symptoms
Why do Trisomies occur?
Due to non-disjunction
What is non-disjunction when can it occur
failure of homologous chromosomes to separate during meiosis I Daughter cells (2 n+1 and 2 n-1)
or
non-disjunction as a result of failure of sister chromatids to separate during meiosis II Daughter cells (n+1, n-1< and two normal haploid n)
incidence of non-disjunction
Increases with increased maternal age
longer oocytes have been left in the dormant stage of meiosis I thought to lead to damage to spindle fibre production and repair mechanisms as woman ages predisposing oocyte to non-disjunction
Edwards and Patau syndrome incidence and symptoms
Edwards 1 in 3000
multiple heart and kidney malformations
Patau 1 in 5000
multiple malformations
Both have poor prognosis baby dies in first few weeks
if they survive have sever mental retardation
