Chromosomal Abnormalities

Question 1

How do you prepare the karyotype

Answer 1

Collect 5 ml heparinised venous blood ( can use amniotic cells, CVS)
Isolate white cells
Culture in presence of phytohaemagglutinin ( stimulates the T lymphocyte growth/differentiation)
After 48 hrs add colchicine - causes mitosis arrest - metaphase
Place in hypotonic saline
Place on slide
Fix and stain with gisema

Question 2

DNA compaction

Answer 2

DNA is condensed into chromatin which is wrapped around his tones. Proteins bound to chromatin affect its regulation and the 3D genome is important.

Question 3

What is the short arm called

Answer 3

P arm

Question 4

What is the long arm of the chromosome

Answer 4

Q arm

Question 5

What is a telomere

Answer 5

The caps at the end of the chromosome

Question 6

Why are the bands different colours

Answer 6

Some areas take up more gisema and appear dark while some areas take up less gisema and appear light

Question 7

Regions of different compaction

Answer 7

Dark ( heteronormative) more compact fewer genes

Light ( euchromatin ) more open more genes

Question 8

What does bphs mean

Answer 8

Bands per haploid set

Question 9

What is karyotype

Answer 9

Chromosome count of individual - can detect major chromosome abnormalities

Question 10

When is karyotyping done

Answer 10

Usually metaphase but also prophase as the chromosomes are less compact and therefore you get more detail from the karyotype

Question 11

Aneuploidy

Answer 11

Abnormal number of chromosomes .you can cope with a missing number of genes but if the chromosomes are missing, the a whole number of genes are affected which causes problems and results in syndromes

Question 12

Chromosome non disjunction

Answer 12

Non disjuncture results in uneven numbers of
Chromosomes in daughter cells .

Can occur in meiosis 1 or 2 .

Meiosis 1 all daughter cells affected
Meiosis 2 , half of daughter cells affected

When fertilised, either trisonomy or monosomy

Question 13

Sex chromosome aneuploidy

Answer 13

Most common form of chromosomal abnormality . Affects more males

Question 14

Why is sex chromosome imbalance tolderated

Answer 14

X inactivation of excess X chromosomes , only one X chromosome active. Low gene content of Y chromosome

Question 15

PAr

Answer 15

Pseudo autosomal region

Question 16

Does the risk of maternal non disjunction increase with age

Answer 16

Yes

Question 17

Why is there a maternal age effect

Answer 17

Vulnerability of oogenesis ( differentiation of ovum)
Paused in Utero in prophase I until puberty
Secondary oocyte arrests in metaphase II
Only competes if fertilised
One primary oocyte yields only one ovum
Finite number of primary oocyte

Question 18

Female non disjunction

Answer 18

Most aneuploidy caused by non disjunction arises in oogenesis

Likely due to degradation of factors which hold homologous chromatids together during metaphase

Question 19

Paternal age effect - spermatogenesis

Answer 19

Vulnerability of male meiosis

Primary spermatocytes undergo approx 23 mitotic divisions per year and potentially accumulate defects

Question 20

Paternal age effect

Answer 20

Paternal age effect affects a subset of single gene disorders caused by point mutations in FGR2 , FgR3 and RET
Eg. Apert syndrome
Crouzon syndrome
Pfeiffer syndrome

Question 21

Trisomy vs monosomy

Answer 21

Most trisomies are not compatible with life and monosomy is very poorly tolerated

Question 22

Crossing over of chromosomes

Answer 22

Occurs in prophase 1
Increases genetic diversity
Pairs of chromosomes align 
Chiasma form and crossover occurs
1-3 times per chromosome per meiosis 
But can go wrong

Question 23

Single chromosome abnormalities

Answer 23

Deletions; Can be the result of unequal cross over
Breaks in chromosome
Can occur at ends

Duplication; most often caused by unequal cross over

Paracentric inversions:
Can cause reproductive problems
Children’s with deletions / insertions

Question 24

Two chromosome abnormalities

Answer 24

Insertions and translocation

If balanced does not affect carrier but may cause problems in off spring
Can cause partial trisomy or monosomy ( cri- du chat syndrome )

Can occur in somatic cells , cf, Philadelphia chromosome, cmL

Question 25

Chromosomal deletions

Answer 25

Can either be microscopic or micro deletion microscopic criminal deletions can be easily detected in microscopes . micro deletions are were 20+ genes can be deleted
Eg cri du chat syndrome

Question 26

Williams syndrome

Answer 26

Deletion

Long philtrum  
Short upturned nose
Arched eyebrows
Suprvalvular aortic stenosis 
Friendly social personality and absence of social anxiety

Phenotypes caused by imbalance of genes which are unrelated apart from their genomic location

Question 27

How can Williams syndrome be detected

Answer 27

Deletion is too small to detec5 using standard karyotyping

Can be detected using targeted FISH
Fluorescent in situ hybridisation - lack of elastin on affected chromosome

Question 28

Difference between 7q11.23 deleti9n ( Williams ) and duplication syndrome

Answer 28

Duplication;
Delayed speech development
Autistic behaviours that affect social interaction and communication
Dilation if the aorta
Flat eyebrows
Broad nose and short philtrum
Duplications usually have a milder phenotype than the reciprocal deletion

Question 29

Classes of chromosomes

Answer 29

Meta centric; short arm and long arm are equal lengths
Submetacentric; short arm is a lot shorter than the long arm
Acrocentric: short arm has been reduced down to a vestigial stump

Question 30

What is a robertsonian translocation

Answer 30

Occurs between acrocentric chromosomes
Most common 13 and 14, 14 and 15 , 14 and 21
Whilst silent in carriers, it can produce affected offspring

Question 31

Mosaicism

Answer 31

Presence of two or more populations of cell with diff genotypes
X inactivation results in mosaic expression
Mosaicism can arise two mechanism;
- non disjuncture during early development
- loss of extra chromosome in early development
Results in Generally milder phenotype
- some lethal aneuploidy survivable if mosaic
Most common mosaic 46,XX /45,X, mosaic 46,day/45,X