Chromosomal Abnormalities (Megee L2, 3)

Question 0

Give some examples of events that induce double strand breaks in the DNA

Answer 0

Ionizing radiation
Meiotic recombination

DNA repair mechanisms can induce double strand breaks

Question 1

What has to happen (structurally) for a chromosomal rearrangement to take place?

Answer 1

two double strand breaks

Question 2

List some results of DSB’s that occur during meiotic recombination

Answer 2

duplications
deletions
insertions
inversions
translocations

Question 3

Where do the breakpoints of duplications, deletions, insertions, translocations and inversions all seem to occur?

Answer 3

Within regions of the chromosome composed of a lot of repeated sequences.

Question 4

What are the two main categories of chromosomal structural rearrangements?

Answer 4

Balanced and Unbalanced

Question 5

What is a balanced rearrangement?

Answer 5

Normal compliments of the genetic material but with varying stability during meiosis and mitosis

Question 6

Give some examples of balanced rearrangements.

Answer 6

Inversion
Reciprocal Translocation
Robertsonian Translocation

Question 7

Describe an inversion rearrangement.

Answer 7

Two double strand breaks on the same piece of DNA. The disconnected sequence is inverted before being reinserted and reconnected.

Question 8

What is a paracentric inversion?

What is a pericentric inversion?

Answer 8

Paracentric: The removed, inverted and reinserted piece does NOT include the centromere.

Pericetric: The removed, inverted and reinserted piece DOES include the centromere.

Question 9

Describe a reciprocal traslocation rearrangement.

Answer 9

Two non-homologous chromosomes basically each swap a piece of their DNA for a piece from the other chromosome.  
ex:
12345				12389
			---->
6789				6745

Question 10

In pericentric inversions, crossovers within the inverted region can produce _________ and ________.

Answer 10

deletions and duplications.

Question 11

In pericentric inversions, crossovers NOT within the inverted region will produce ____________ gametes.

Answer 11

balanced (full chromosomal compliment with the inversion)

Question 12

In paracentric inversions, crossovers within the inverted region can produce _________ and ________.

Answer 12

dicentric and acentric

Question 13

Individuals with balanced chromosomal rearrangements are “likely” to be ________.

Answer 13

phenotypically normal…but it really depends on the specific rearrangement

Question 14

Suppose an individual has a reciprocal translocation in their chromosomes. At anaphase, a __________ figure is formed and segregation can be _______, _______ or ________.

Answer 14

quadravalent
alternative (normal or balanced)
adjacent 1 (unbalanced)
adjacent 2 (unbalanced)

Question 15

Chronic myelogenous leukemia is caused by translocation of chromosomes ________ and _________

Answer 15

9 and 22 (q34;q11.2)

female

Question 16

Describe a Robertsonian Translocation

Answer 16

Fusion of two acrocentric cromosomes within the centromeric regions.

Question 17

What is lost during Robertsonian Translocation and why is this “O.K.”?

Answer 17

loss of the satellite and stalk DNA from the small arm of the original acrocentric chromosomes.

is “O.K.” because there is redundancy of the ribosomal DNA contained in the stalk region on the other acrocentric chromosomes.

Question 18

What is the likely bad outcome of an individual with a Robertsonian Translocation?

Answer 18

It is likely that their offspring will have an abnormal kayrotype (monosomy and trisomy)

Question 19

Which particular Robertsonian Translocation did Dr. Megee discuss in lecture?

Answer 19

a Robertsonian Translocation involving chromosome 21 can give rise to trisomy 21 in the individuals offspring.

Question 20

What is an unbalanced structural chromosomal rearrangement?

Answer 20

the chromosome has additional or missing material

phenotypes are likely abnormal

Question 21

List the various unbalanced strctural chromosomal rearrangements.

Answer 21

1. Deletion
2. Duplication
3. Ring Chromosome
4. Isochromosome

Question 22

Describe a deletion unbalanced chromosome.

Answer 22

chromosome set has missing or additional genetic material

Question 23

Chromosome ____ is most commonly involved in Robertsonian Translocation

Answer 23

14

Question 24

Describe a terminal deletion.

Answer 24

When a deletion involved the end of a chromosome arm.

Question 25

Describe an interstitial chromosomal deletion.

Answer 25

When the deletion is within a chromosomal arm. Can result in acentric and/or a-telomeric fragments.

Question 26

What is a ring chromosome and how is it produced?

Answer 26

An interstitial deletion can result in an acentric or centric fragment that forms a ring. The acentric ring is not stably transmissible.

Question 27

What is an isochromosome?

Answer 27

A chromosome in which one arm is deleted and the other is duplicated in a mirror-image fashion. Can result in monosomy and trisomy OR tetrachromosomy. Trisomy of the mirrored arm and monosomy of the deleted arm. (there's still one copy of that arm on the homologue) OR Tetrasomy when the isochromosome ins in addition to the two normal homologues.

Question 28

What is the most common isochromosome?

Answer 28

The long arm of the X chromosome, i(Xq) Appears in individuals with Turner Syndrome.

Question 29

What is a dicentric chromosome?

Answer 29

When two chromosome segments, each with a centromere, fuse end to end. Can be two different chromosomes or two chromatids of the same chromosome.

Question 30

What is haploinsufficiency?

Answer 30

Inability of a single copy of the genetic material to carry out the functions normally performed by two copies.

Question 31

Contiguous Gene syndrome is caused by...

Answer 31

Deletion of multiple contiguous genes; deletion due to abherent recombination between repetitive sequences.

Question 32

What are some clinical findings that warrant investigation into possible sex chromosome abnormalities?

Answer 32

1. delay in onset of puberty 2. primary or secondary amenorrhea 3. infertility 4. ambiguous genitalia

Question 33

Phenotypes associated with X and Y chromosomal defects are, in general, less severe than autosomal disorders because...

Answer 33

X inactivation and the small number of genes located on the Y chromosome