Chromosomal Abnormalities

Question 1

Karyotype defination?

Answer 1

Individual collection of chromosomes

Also refers to lab technique to produce an image of it

Question 2

Method of making a karyotype?

Answer 2

5ml heparinised venous blood
Isolate w.b.c
culture with phytohaemagglutinin
48 hours later add colchicine
place in hypotonic saline
place on slide
fix and Gisema stains (nucleic acid stain)

Question 3

What does Heparin do?

Answer 3

Stops Coagulating

Question 4

What does phytohaemagglutinin do?

Answer 4

(PHA) Stimulates T-lymphocyte growth bye mitotic stimulation

Question 5

What does colchicrine do?

Answer 5

The effect of colchicine, which inhibits microtubule polymerization and thus assembly of the mitotic spindle, demonstrates the presence of another checkpoint in the cell cycle. When colchicine is added to cultured cells, the cells enter mitosis and arrest with condensed chromosomes.

Question 6

What are Ideogram?

Answer 6

Ideograms are diagrammatic or idealized representations of chromosomes, showing their relative size, homologous groups and cytogenetic landmarks.

Question 7

What is the P-arm and Q-arm

Answer 7

Petite arm, long arm. connected at centromere.

Question 8

What are band number?

Answer 8

Chromosome banding refers to alternating light and dark regions along the length of a chromosome, produced after staining with a dye
due to new techniques, have sub-bands.

Nomenclature example : 3p21 - Chromosome 3, petite arm, band 2, sub band 1

Question 9

What is bphs?

Answer 9

bands per haploid set

dark bands (heterochromatin) -fewer compact genes
light bands (euchromatin) more open genes

Question 10

What is Aneuploidy?

Answer 10

Abnormal number of chromosomes

Question 11

Non Disjuncture can result in ?

Answer 11

Trisomy or Monosomy

Question 12

Pseudo-autosomal region

Answer 12

region which does not get inactivated during X chromosomal inactivation, (is on both y and x chromosome)

Question 13

Trisomy 21

Answer 13

Risk of maternal non-disjunction increases w/age e.g. trisomy 21 (Down’s syndrome)

Can see 3 chromosome 21s in karyotype

Can see amounts of DNA as well using QF-PCR (quantitative fluorescence PCR)

Question 14

Oogenesis and female disjunction

Answer 14

Most aneuploidy caused by non-disjunction arises in oogenesis. likely due to degradation of factors which hold homologous chromatids together

Question 15

Paternal affect on anueploidy?

Answer 15

Affect single gene disorders by point mutation sin FGFR2, FGFR3, RET
Apert syndrome
Crousen syndrome
Pfeiffer syndrome

Question 16

Single chromosome abnormalities

Answer 16

(during crossing over) Deletion, duplication, most caused by unequal cross overs

paracentric inversion: inverted segment in single chromosome
pericentric inversion: inverted segment at centromere
–> carriers often unaffected but can cause reproductive problems

Question 17

What is selfish spermatogonial selection?

Answer 17

Mutated spermatogonia undergo favoured mitosis in comparison to neighbouring wild type cells. Paternal age is not a risk factor for increased aneuploidy like oogenesis is but spermatocytes may accumulate defects over time.

Question 18

Two chromosome abnormalities

Answer 18

If both chromosomes remain balanced the carrier will not have problems but may cause problems in off spring.

Can cause partial trisomy or monosomy.

Question 19

Chromosomal deletion examples?

Answer 19

Cri-du-chat syndrome 46,XY,del(5p)

Can be detected easily by microscope

Question 20

Microdeletion in chromosomes?

Answer 20

Seen in high resolution banding, molecular genetics
20+ genes deleted
Velocardiofacial/DiGeorge syndrome 22q11.2 del

Question 21

Williams Syndrome 7q11.23 deletion Phenotype?

Answer 21

(lacking elastin gene)
Long philtrum
Short upturned nose
arches eyebrows
absence of social anxiety

Question 22

If abnormality too small to be seen on karyotype? E.g. Williams syndrome deletion

Answer 22

Targeted FISH

Fluorescent in situ hybridisation

Question 23

Duplication Syndrome 7q11.23 Phenotype

Answer 23

Delayed speech development, autistic behaviours, dilation or aorta, flat eyebrows, broad nose and short philtrum.

Duplication usually have a milder phenotype than reciprocal deletion of same gene

Question 24

What are Metacentric chromosomes?

Answer 24

centromere is in middle, meaning p and q arms are of comparable length

Question 25

What are Submetacentric Chromosomes?

Answer 25

centromere off-centre, leading to shorter p arm relative to q arm

Question 26

What are Acrocentric Chromosomes?

Answer 26

centromere severely off-set from centre, leading to much shorter p arm. Has Stalk and Satellite at top of P arm

Question 27

What is Robertsonian translocation?

Answer 27

Occurs between acrocentric chromosomes
Common: 
13 + 14 , 
14 + 15, 
14 + 21

Unaffected people - can have balanced genotypes, problems in offspring

Question 28

What is Mosaicism?

Answer 28

Presence of 2+ populations of cells with different genotypes caused by X-inactivation

Question 29

What are the 2 mechanisms of Mosaicism?

Answer 29

Non-disjuncture during early development
Loss of extra chromosome in early development (this can also turn lethal aneuploidy survivable with less severe phenotype)