MG: lec 5

Question 1

What are structural chromosomal anomalies?

Answer 1

A change in a part of a given chromosome:
1. translocation
2. insertion
3. inversion
4. duplication
5. deletion
6. isochromosomes
7. ring chromsomes
8. fragile chromsomes (fragile X syndrome)

Question 2

What is translocation and the types of translocation?

Answer 2

When a part of a chromsome switched to another chromosome.
1. the most common type: Robertsonian translocation
2. reciprocal translocation

Question 3

What is a reciprocal translocation?

Answer 3

When a segment splits off of the two chromosomes involved, resulting in an exchange of these segments which forms two new derivative chromosomes.

Question 4

What is Robertsonian translocation?

Answer 4

It is a type of reciprocal translocation that is specific to the acrocentric chromosomes where the breakpoint is near or at their centromere.
- between 2 acrocentric chromosomes

Question 5

What is the difference between the derivative chromosomes of a Robertsonian translocation and any other reciprocal kind?

Answer 5

It results in 1 chromosome with both ends of the centromere being long arms, each pair from 2 different chromosomes. The reciprocal, however, will produce 2 chromosomes, as their short arms are not lost.

Question 6

How can the exchanged fragments in a reciprocal translocation be identified?

Answer 6

only by 2 methods:
- detailed chromosomal banding studied
- FISH Fluorescence in situ hybridization

Question 7

What is the karyotype notation of a Robertsonian translocation where the short arms of 13 and 14 are lost?

Answer 7

45, XX, der(13;14)(q10;q10)
- q10 denotes the breakpoint (centromere region)
- q is the long arm
- der comes from “derived chromosome”

Question 8

Which are the acrocentric chromosomes?

Answer 8

13, 14, 15, 21, 22

Question 9

What does this karyotype mean: 46,XY,t(6;9)(q24;p22)

Answer 9

• 46: full set of chromosomes (switching segments only, so reciprocal translocation)
• XY: male
• t means translocation
• (6;9) means switching between chromsomes 6 and 9
• (q24; means region 2 of chromosome 6, band 4, on its long arm
• p22) means region 2, band 2 of chromosome 9 on its short arm

Question 10

46,XY,ins(4;20)(q21;q32q41)

Answer 10

• 46 means it’s a full set
• XY male
• ins means insertion
• (4;20) part of 4 has been moved to chromosome 20
• (q21) region 2, band 1 of the long arm of chromosome 4 is being moved
• (q32q41) has been inserted between region 3, band 2 and region 4, band 1 of the long arm.

Question 11

How are the regions and bands numbered?

Answer 11

regions: from the centromere, outward
bands: increase towards the telomeres (band 1 at the start of each region)

• region is the G and R bands

Question 12

What is an inversion?

Answer 12

When a segment breaks off between two points within a chromosome and reinserts itself in reverse in the same chromosome arm

Question 13

What is notable about the nature of these breakpoint in an inversion chromosomal abnormality?

Answer 13

The breakpoints of inversions often happen in regions of repetitive nucleotides.

Question 14

What are the types of inversions?

Answer 14

1. paracentric inversion
2. pericentric inversion

Question 15

Inversion including the centromere:

Answer 15

pericentric

Question 16

Paracentric inversions:

Answer 16

Contain 2 breakpoints within an arm; do not include the centromere

Question 17

interpret: 46,XY,inv(2)(p12p24)

Answer 17

46 means full set
XY male
inv inversion
(2) happening on chromosome 2
(p12 first breakpoint is in region 1, band 2 of the short arm
p24) inverse segment ends at the second region, band 4 of the same short arm

Question 18

Which is the pericentric inversion and why?

Answer 18

no. 3 since it “goes over” of the centromere

Question 19

What is duplication?

Answer 19

A gain of chromosomal material
“genetic overdose”

Question 20

Interpret: 46,XX,dup(17)(q12)

Answer 20

• 46 means an additional chromosome
• XX means female with normal sex chromosomes
• dup means duplication
• 17 means autosomal chromsome, no. 17, is duplicated
• q12 means long arm’s region 1, band 2 is duplicatied

Question 21

In the duplication 46,XX,dup(17)(q12), what does the duplication result in?

Answer 21

A small piece of chromosome 17 being abnormally copied in each cell

Question 22

Types of deletion

Answer 22

1. interstitial deletion
2. terminal deletion

Question 23

What is interstitial deletion

Answer 23

when the terminal ends of an arm (the telomeres) remain intact following the loss of an internal segment in the chromosome that breaks off from 2 breakpoints (does not relocate, just diminishes)

Question 24

What is terminal deletion

Answer 24

when the break is near the end of the chromosome arm, so the telomere gets broken off as well.
- all genetic material from the breakpoint to the tip of the chromosome is lost

Question 25

What is an example of a deletion structural anomaly?

Answer 25

Cri du Chat syndrome: terminal deletion

Question 26

What is Cri du Chat syndrome?

Answer 26

(example) karyotype notation: 46,XX,del(5)(p-) simply noted as "5p-"

Question 27

What are the major clinical features of Cri du Chat syndrome?

Answer 27

- cat-like cry - microcephaly - hypotonia - hypertelorism - severe metal and developmental retardation - low-set ears - moon-shaped face

Question 28

Prevalence of Cri du Chat

Answer 28

- 1 in 20 000 to 50 000 newborns - not-ethnically tied - since it's the end of p5, the length of that deletion varies amongst individuals - the larger the deletion, the more severe the disability

Question 29

What is an isochromosome?

Answer 29

When a chromosome as 2 copies of the long or short arm - looks like a Robertsonian translocation where both arms are long, except this is from **one chromosome**

Question 30

How does an isochromosome form?

Answer 30

simultaneous duplication and deletion of genetic material - partial trisomy in one set genes, partial monosomy in the other set of genes on the lost arm(s)

Question 31

What is a clinical example of an isochromosome?

Answer 31

Medulloblastoma

Question 32

What is medulloblastoma?

Answer 32

CNS neoplasia form - isochromosome of no.17: two long arms

Question 33

What is the notation of Medulloblastoma?

Answer 33

i(q17)

Question 34

How is medulloblastoma diagnosed?

Answer 34

in the lab: FISH, or karyotype? | check

Question 35

Why do isochromosomes occur?

Answer 35

Likely due to a transverse division of the centromere rather than a longitudinal one - a common one is of the long arms of the X chromosome (15% of Turner's syndrome cases)

Question 36

What is a ring chromosome?

Answer 36

- when a break occurs on each arm of a chromosome; both its long and short arm - break happens near the telomeres

Question 37

What is the common ring chromosome abnormality?

Answer 37

chromsome 18: loss of the **caps** of both long and short arm in one copy of no. 18 (maternal OR paternal)

Question 38

What is a fragile chromosome?

Answer 38

A specific heritable point on a chromosome that tends to form a gap/ constriction that may tend to break when the cell is exposed to "**partial replication stress**

Question 39

How are "fragile sites" classified?

Answer 39

Common or rare, depending on their frequency

Question 40

How many fragile sites have been identified in the human genome?

Answer 40

120 fragile sites