Chromasomal Abnormalities

Question 1

What is a karyotype?

Answer 1

A persons collection of chromosomes

Question 2

How might a persons karyotype be determined?

Answer 2

Using peripheral blood

1. Collect around 5ml of heparinised blood
2. Isolate white cells
3. Culture in presence of phytohamagglitanin (this stimulates T cell growt)
4. After 48 hours add colchicine (causes mitotic arrest during metaphase)
5. Place in hypotonic saline (to burst cells)
6. Fix and stain with gisema

Question 3

How is DNA compacted?

Answer 3

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

Question 4

What is an ideogram?

Answer 4

Shows the structure of a chromosome

Question 5

What are some features of a chromosome on an ideogram?

Answer 5

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

Question 6

The pattern left by gisema staining is labelled numerically. What do the numbers mean?

Answer 6

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

Question 7

How is the resolution on a karyotype described?

Answer 7

Eg. 400 bphs

Bphs : bands per haploid set

Question 8

What do the bands on a karyotype show?

Answer 8

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

Question 9

What is aneuploidy?

Answer 9

An abnormal number of chromosomes

Ie not 46

Question 10

What is the process of meiosis?

Answer 10

To achieve a reduction from diploid to haploid number

Ensures genetic variation

And enables random assortment of homologues and recombination

Question 11

What is non disjunction?

Answer 11

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)

Question 12

What is the most common form of aneuploidy?

Answer 12

Sex chromosome aneuploidy

Question 13

What is sex chromosome aneuploidy?

Answer 13

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

Question 14

What is the second most common form of aneuploidy?

Answer 14

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

Question 15

What are the pregnancy risks associated with aneuploidy?

Answer 15

Contributes to 5% of still births and 50% of miscarriages

Most trisomies are not compatible with life,
Monosonomies are very poorly tolerated

Question 16

What are some abbreviations?

Answer 16

Del - deletion

Der - derivative chromosome (extra material)

Dup - duplication

Ins - insertion

INV - inversion

T - translocation

Cen - centromere

Question 17

When does crossing over occur and what is it?

Answer 17

Prophase I

Increases genetic diversity

Paris of chromosomes align, chiasma form and crossover occurs

1-4 times per chromosome per meiosis

Sometimes goes wrong

Question 18

How can crossing over go wrong?

Answer 18

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

Question 19

What are some single chromosome abnormalities?

Answer 19

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

Question 20

What are two chromosome abnormalities?

Answer 20

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

Question 21

What are the categories of chromosomal deletions?

Answer 21

Microscopic - can be easily detected my microscope

Microdeletion- only seen in high resolution banding, or with molecular genetics

Question 22

What is a robertsonian translocation?

Answer 22

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

Question 23

What are the three classss of chromosomes?

Answer 23

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)

Question 24

What is mosaicism?

Answer 24

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