chromosomes and chromosomal abnormalities Flashcards
in what 3 ways is a chromosome recognised?
- banding pattern with specific stains (each chromosome looks different and can be classified)
- length
- position of centromere
what is a feature of acrocentric chromosomes?
what chromosomes within humans are acrocentric chromosomes?
acrocentric chromosomes: the short arm of the chromosome is so smol that it doesn’t count for much
- The chromosomes are divided into two parts with a point of constriction in the center, known as the centromere.
- An acrocentric chromosome isone in which the centromere is located near the end of the chromosome
- Humans usually have five pairs of acrocentric chromosomes (Ch 13,14, 15, 21, 22)
what are 3chromosome changes that cause disease?
- balanced chromosome rearrangement
- all the chromosomal material is present (no loss of information, just movement of location)
e.g translocation, inversions
- all the chromosomal material is present (no loss of information, just movement of location)
- unbalanced chromosome rearrangement
- extra or missing chromosomal material (loss of information as well as rearrangement)
- usually 1 or 3 copies of some of the genome
e.g insertions, deletions, duplications
- having 1 or 3 copies of a part of your genome is developmentally bad news
e.g aneoploidy (whole extra/missing chromosome)
when does aneuploid and non-disjunction occur?
what are 3 most common trisomies?
- occurs during meiosis steps of production of sperm/egg
- mutations occur and are inherited in the fertilised embryo
47XY + 21 = Trisomy 21 :Down syndrome - one extra copy of Ch21
47XY + 18 = Trisomy 18 :Edward Syndrome - one extra copy of Ch18
47 XX + 13 = Trisomy 13 :Patau syndrome - one extra copy of Ch13
rapid prenatal diagnosis:
when is Fluorescence In Situ Hybridization (FISH) used?
how does it work?
FISH (fluorescence In Situ Hybridization): used when you know what your looking for
-is done through interphase chromosome counting
- looking at foetal cells during interphase, red stain = DNA nuclei and yellow stain = nucleic acid probe which is linked to fluorophores which is designed for a particular part of the genome: a chromosome 18 markers
- normal situation, diploid genome so two signals seen - in trisomy 18, three signals seen
when is Array Comparative Genome Hybridisation (Array CGH)
how does it work?
- Array CGH (comparative genome hybridisation): looking across the genome, when your looking for more than one event at the same time and are seeing for any changes
- still fluorescence based technology: labels control DNA (red) and patient DNA (green)
- patient and control DNA are labeled with fluorescent dyes and applied to the microarray
- patient and control DNA compete to attach, or hybridize, to the microarray
- the microarray scanner measures the fluorescent signals
- computer software analyzes the data and generates a plot
- equal amounts = yellow
- DNA loss = more red
- DNA gain = more green
what are 3 associated syndromes in which there are defects in whole chromosome number?
45X : turner syndrome
- females, inheriting only 1 X chromosome, rather than 2
47 XXX : Triple X
- females, inheriting 3 X chromosomes (2 inactivated and 1 normal, however this imbalance still causes a change in phenotype)
47 XXY : Klinefelter syndrome
- X chromosome aneuploidy is better tolerated because of X inactivation
- male
what are two major two chromosome mutations?
- chromosomal insertion and chromosomal translocation
what is robertsonian translocation?
- robertsonian translocation: two acrocentric chromosomes stuck end to end
- increased risk of trisomy in a pregnancy (miscarriage/down syndrome), often robertsonian translocation has no phenotype
what is reciprocal translocation?
what are the reproductive risks of reciprocal translocations?
reciprocal translocation: moving two bits of information (swapping event)
- for most translocations, about 50% of conceptions will have either normal chromosomes or the balanced translocation
- however the other 50% of unbalanced products result in:
- miscarriage (large segments)
- dysmorphic delayed child (small segments)
describe the Philadelphia chromosome
a specific genetic abnormality in chromosome 22 of leukemia cancer cells
- consistant translocation swapping event with chromosome 9 and chromosome 22
- fusion event of a protein (bcr stuck to abl)
single chromosome mutations:
describe deletion, duplication and inversion mutations
- deletion, area of chromosome removed
- duplication, area of chromosome duplicated and translocated in the same region
- inversion, positional change in which there is a flipping of locus
give an example of a chromosomal deletion event:
X linked ichthyosis: A genetic skin disorder that causes drying, the formation of scales and thickening of the skin
give an example of a chromosomal duplication event:
charcot marie tooth disease:
- nerve damage to myelin sheath in peripheral nerves - causing progressive loss of muscle tissue and touch sensation
- mutations in 39 genes can cause CMT
- commonest form is within certain gene chromosome 17: CMT1A - 70 - 80% cases have large duplication of 17p11.2
