Genetics - Chromosomal Abnormalities

Question 1

What is a karyotype?

Answer 1

Collection of chromosomes

Question 2

What can we use for a karyotype sample?

Answer 2

Peripheral blood, amniotic cells, CVS

Question 3

If using peripheral blood for karyotype, what must we do?

Answer 3

• Isolate white blood cells
• Then culture cells in presence of phytohemagglutin, which will stimulate T cell growth and differentiation.
• Then, after 48 hours add colchicine to arrest mitosis.
• Place cells in hypotonic solution - cause lysis
• Stain with giemsa and observe results

Question 4

What is an ideogram?

Answer 4

The distinct pattern a chromosome generates with giemsa

Question 5

What is the p-arm?

Answer 5

Short arm

Question 6

What is the q-arm?

Answer 6

Long arm

Question 7

What are g-dark bands?

Answer 7

Dark bands of chromosome which take up more gisema

Question 8

what are g-light bands?

Answer 8

Light bands of chromosome which take up less gisema

Question 9

What does 3p21 mean?

Answer 9

Region found on chromosome 3, p arm, 2nd band, 1st region of 2nd band.

Question 10

Why are dark bands dark?

Answer 10

They take up more gisema which is used to stain the chromosomes

Question 11

What is contained in dark bands?

Answer 11

Heterochromatin which contain few, more dense genes so take up more gisema

Question 12

What is contained in light bands?

Answer 12

Euchromatin with less, more open genes so take up less gisema

Question 13

What is aneuploidy?

Answer 13

Abnormal number of chromsomes

Question 14

What is the purpose of meiosis?

Answer 14

Achieve reduction of diploid to haploid
Achieve genetic variation
Enable random assortment of homologues and recombination

Question 15

What is non disjunction?

Answer 15

When chromosomes don’t split properly between daughter cells

Question 16

When does non disjunction occur?

Answer 16

Either meiosis 1 or 2

Question 17

What does M1 non disjunction mean?

Answer 17

All daughter cells are affected

Question 18

What does M2 non disjunction mean?

Answer 18

Only half of the daughter cells are affected

Question 19

What does non disjunction always result in?

Answer 19

Either trisomy or monosomy after fertilisation

Question 20

What is the most common abnormality?

Answer 20

Sex chromosome aneuploidy

Question 21

Why is a sex chromosome imbalance tolerated?

Answer 21

1. Only part of one of the X chromosomes in females in inactivated
2. Y chromosome has few genes
3. Pseudo autosomal region (PAR) - part of the X chromosome is not inactivated along with the X chromosome.

Question 22

What is trisomy 21?

Answer 22

Dow’s syndrome: 3 copies of chromosome 21

Question 23

When do most cases of Downs arise?

Answer 23

Maternal oogenesis

Question 24

Is there paternal input in Downs?

Answer 24

Some

Question 25

What increases the risk of Downs?

Answer 25

Maternal age (positive correlation)

Question 26

Why is there a maternal age effect on Downs?

Answer 26

1. Inherent vulnerability of oogenesis with age 2. Primary oocytes are produced in utero before prophase 1 and then arrested until puberty 3. Secondary oocytes arrest in metaphase 2 until fertilisation. This causes the degradation of factors which hold chromatids together during division

Question 27

Does paternal age influence aneuploidy?

Answer 27

No, however it has an effect on single gene disorders

Question 28

How do spermatocytes influence aneuploidy?

Answer 28

Primary spermatocytes undergo 23 mitotic divisions per year

Question 29

What is selfish spermatogonial selection?

Answer 29

Mutated spermatids may have an advantage over wild type spermatids

Question 30

What is a paternal but not maternal risk factor for Downs?

Answer 30

Smoking

Question 31

What is the effect of aneuploidy on pregnancy?

Answer 31

5% of still births and 50% of abortions/miscarriages are due to anueploidy

Question 32

How can we detect trisomy?

Answer 32

Prenatally

Question 33

Why is there little monosomy?

Answer 33

Poorly tolerated, trisomy is also often incompatible with life

Question 34

When do cross over chromosomes occur?

Answer 34

Prophase 1

Question 35

What does cross over do?

Answer 35

Increases genetic diversity

Question 36

What is cross over?

Answer 36

Pairs of chromosomes align, chiasma form and cross over between chromosomes occur

Question 37

How often does cross over occur?

Answer 37

1-3 times per chromosome per meiosis

Question 38

What happens when cross over goes wrong?

Answer 38

Unequal crossover can cause duplication in one chromosome and deletion in the other chromsome

Question 39

What are examples of single chromosome abnormalities?

Answer 39

Deletion Duplication Inversion

Question 40

What is deletion?

Answer 40

part of chromosome deleted

Question 41

What is duplication?

Answer 41

part of chromosome added onto same chromosome

Question 42

What is inversion?

Answer 42

Section of chromosome is turned upside down to sometimes cause reproductive issues

Question 43

What is insertion?

Answer 43

Two chromosomal abnormality - unidirectional manner of transfer from one chromosome to another

Question 44

What is translocation?

Answer 44

Mutual exchange where different derivative chromosomes are formed after a swap of genetic material

Question 45

What is an example of translocation mutation?

Answer 45

Philadelphia chromosome (CML)

Question 46

Are abnormalities always inherited?

Answer 46

No: many are de novo. | Some people are unidentified carriers and can have offspring who are affected

Question 47

What are microscopic deletions?

Answer 47

Deletion easily detected with microscope and staining e.g. Cri-du-chat syndrome - deletion of whole p arm of chromosome 5

Question 48

What are microdeletions?

Answer 48

Can only be seen in very high resolutio banding e.g. DiGeorge Syndrome - deletion of one sub band

Question 49

What occurs in William's syndrome?

Answer 49

Gene on long arm of chromosome 7 is deleted

Question 50

Why can't we use a normal karyotype for detecting William's?

Answer 50

Too small to detect

Question 51

What can we use to detect Williams?

Answer 51

Fluorescent in situ hybridisation (FISH assay)

Question 52

What are the symptoms of Williams?

Answer 52

Long philtrum Short, upturned nose Supravalvular aortic stenosis No social anxiety - friendly

Question 53

What is the result of a reciprocal duplication that occurs in the same area affected by Williams?

Answer 53

Opposite symptoms of William's e.g. autistic traits, broad nose and short philtrum

Question 54

Phenotypically, how do duplications differ to deletion?

Answer 54

Generally, duplications have a milder phenotype than deletions

Question 55

What are the 3 classes of chromosomes?

Answer 55

- - Metrocentric - short P arm, long Q arm, centromere in centre - - Submetacentric - short arm is considerably shorter than long arm - - Acrocentric - short arm reduced to stalk or satellite.

Question 56

What is Robertsonian translocation?

Answer 56

When two acrocentric chromosomes lose their stalks and their long arms combine to form a derivative chromosome Can be homologous or non homologous

Question 57

Why are most carriers of Robertsonian translocation unaffected?

Answer 57

If it occurs during development, they will have a balanced genotype and it only evolves one of each of the 2 chromosomes

Question 58

Why may carrier offspring not be affected?

Answer 58

If a carrier is homologous, they will have one normal copy of a chromosome which can still be inherited normally.

Question 59

Which chromosome pairs are most commonly affected by Robertsonian translocation?

Answer 59

13 and 14 14 and 15 14 and 21

Question 60

What is mosaicism?

Answer 60

Cells of the same population don't contain the same chromosomes

Question 61

How may mosaicism arise?

Answer 61

Non disjunction during early development | Loss of extra chromosome in early development

Question 62

How common is mosaicism?

Answer 62

Everyone is thought to be mosaic

Question 63

What is the most common mosaic?

Answer 63

46, XX/45,X | 46,XY/45,X