Chromasomal Abnormalities Flashcards
What is a karyotype?
A persons collection of chromosomes
How might a persons karyotype be determined?
Using peripheral blood
- Collect around 5ml of heparinised blood
- Isolate white cells
- Culture in presence of phytohamagglitanin (this stimulates T cell growt)
- After 48 hours add colchicine (causes mitotic arrest during metaphase)
- Place in hypotonic saline (to burst cells)
- Fix and stain with gisema
How is DNA compacted?
Double helix, associates with histones. This is coiled to form chromatin fibres.
Chromatin fibres are coiled to form chromatin. Then forms duplicated chromosomes.
The cooking affects its shape
What is an ideogram?
Shows the structure of a chromosome
What are some features of a chromosome on an ideogram?
Centromere - between the two arms
Telomere - at either end
P-arm - the short arm
Q-arm - the long arm
G-dark and G-light - patterns of staining left by gisema
The pattern left by gisema staining is labelled numerically. What do the numbers mean?
Bands are formed by different absorbtion of the stain
Originally at a low resolution so few bands were seen per chromosome. When higher resolutions became available these original bands were split. These were then split once more
Numbers increase outwards from the centromere
Eg 3p22.1 : chromosome 3, short arm, big band 2, smaller band 2, smallest band 1
How is the resolution on a karyotype described?
Eg. 400 bphs
Bphs : bands per haploid set
What do the bands on a karyotype show?
Levels of compaction
Dark bands (heterochromatin) is more compact and fewer genes
Light bands (euchromatin) more open and more genes
Originally this was done in metaphase, but now it is more done in prophase. It can also be done with fluorescent markers
What is aneuploidy?
An abnormal number of chromosomes
Ie not 46
What is the process of meiosis?
To achieve a reduction from diploid to haploid number
Ensures genetic variation
And enables random assortment of homologues and recombination
What is non disjunction?
Chromosomes don’t split properly
Can occur in meiosis I or meiosis II
If it occurs in I all daughter cells are effected, if in II only half
After fertilisation it always results in trisomy or monosonomy (should be 2)
What is the most common form of aneuploidy?
Sex chromosome aneuploidy
What is sex chromosome aneuploidy?
Most common chromosomal aneuploidy. Affects 1/400 males and 1/650 females
But it can be tolerated, how?
X-inactivation : one chromosome is inactivated
Few genes in the Y chromosome, so has little effect
PAR - pseudo autosomal region
What is the second most common form of aneuploidy?
Trisonomy 21 - Down’s syndrome
Most arise from maternal non disjunction
The risk of this increase with age, exponential rise as maternal age increases from 35-40. (Although doesn’t increase in men)
At age 40 it’s 1/40
Oof sneaks is halted at different stages, forst at puberty, then until fertilisation. This means the oocyte has been lying dormant for 40 years. This could lead to degradation
What are the pregnancy risks associated with aneuploidy?
Contributes to 5% of still births and 50% of miscarriages
Most trisomies are not compatible with life,
Monosonomies are very poorly tolerated
What are some abbreviations?
Del - deletion
Der - derivative chromosome (extra material)
Dup - duplication
Ins - insertion
INV - inversion
T - translocation
Cen - centromere
When does crossing over occur and what is it?
Prophase I
Increases genetic diversity
Paris of chromosomes align, chiasma form and crossover occurs
1-4 times per chromosome per meiosis
Sometimes goes wrong
How can crossing over go wrong?
Unequal crossover - the pairs of homologous chromosomes don’t align properly. This leads to a duplication in one chromosome and a deletion in the other
What are some single chromosome abnormalities?
Deletion - can be the result of unequal crossover. Breaks in chromosomes
Duplication - most often caused by unequal crossover
Inversion - can occur on the arms or in the centre. Estimated to occur in 1/1000 people
What are two chromosome abnormalities?
You can get transfer of DNA between non homologous pairs
If unidirectional - gives an insertion and a deletion
Or translocation - they swap some DNA
Carriers are unaffected, but their offspring may be
What are the categories of chromosomal deletions?
Microscopic - can be easily detected my microscope
Microdeletion- only seen in high resolution banding, or with molecular genetics
What is a robertsonian translocation?
Occur in acrocentric chromosomes
Affects 1/1000 people
Can be homologous or not homologous
Translocation occurs which results in both of the stumps getting rid of, leaving one really long chromosome
Most people are unaffected but offspring may not be
What are the three classss of chromosomes?
Metracentric - p and q are roughly the same length
Submetracentric - p is much shorter than q
Acrocentric - the p arm is reduced to a vestigial stump (chromosome 13,14,15,21,22)
What is mosaicism?
Presence of two or more populations of cells with different genotypes
X inactivation results in mosaic expression
True mocaisim arises by two mechanisms:
-non disjuncture during early development
- loss of a tea chromosomes in early development
Normally results in a milder phenotype, but also can make some lethal aneuploidys survivable
