Chromosomal Structural Abnormalities

Question 0

What is an isochromosome?

Answer 0

A duplication of a single chromosome’slong arm and loss of its short arm.

Question 1

What is a Robertsonian translocation?

Answer 1

Fusion of the king arms of two different chromosomes with loss of each chromosomes short arms.

Question 2

What two causes can result in a chromosomal deletion?

Answer 2

1) double stranded breakage and subsequent loss of a acentric fragment
2) unequal crossing over between misaligned homologues

Question 3

What disease does a chromosomal deletion of of the PMP22 gene result in?

Answer 3

HNLPP ( the chromosome that got the duplicated gene leads to CMT)

Question 4

What disease results from a deletion of part of chromosome 5’s p region and how is this deletion acquired?

Answer 4

Cri-du-chat is mostly due to sporadic cases, but about 10% are due to parental translocations.

Question 5

Which of the following is not a symptom of cri-du-chat?
Moderate to severe mental retardation
Microencephaly
Hypertelorism
Epicanthal folds
Low set ears
Heart defects
Renal anomalies
Childhood death likely
Low IQ in adults

Answer 5

Renal anomalies are seen in Turner syndrome

Question 6

True or false: the genes in chrom 5p that’s result in cri-du-chat symptoms when deleted are unknown.

Answer 6

False: many of the genes responsible for the symptoms are known.

Question 7

What syndrome does a deletion in chrom (4)(p16) result in and how does this deletion come about?

Answer 7

Wolf-Hirschhorn syndrome results mostly from sporadic cases, bit about 10% are a consequence of parental translocations.

Question 8

Which of he following is not a symptom of Wolf-Hirschhorn syndrome?
Mental retardation
Growth retardation
Hypertelorism
Long protruding forehead
Cleft lip and palate
Broad nasal bridge
Microcephaly
Heart defects
Seizures

Answer 8

Long protruding foreheads are seen in Patau syndrome (trisomy 13)

Question 9

What is the problem that deletion or insertion mutations cause?

Answer 9

It can result in a partial trisomy.

Question 10

What leads to a duplication mutation?

Answer 10

Unequal crossing over between misaligned homologues.

Question 11

What results in an insertion mutation?

Answer 11

Breakage and subsequent insertion of an acentric fragment into another chromosome or itself in a non-adjacent area.

Question 12

What structure is formed when homologues line up during metaphase if one homologue has an inversion mutation?

Answer 12

Inversion loop

Question 13

True or false: paracentric inversions cannot be detected with CGH hybridization; banding or FISH must be used.

Answer 13

True

Question 14

True or false: most inversion mutations are detected at birth.

Answer 14

False: inversion mutations usually do not result in viable offspring due to an imbalance in genes.

Question 15

True or false: pericentric inversions do not result in gene duplications or deletion a on the chromosomes that underwent crossing over.

Answer 15

False

Question 16

True or false: crossing over outside of inversions do not result in unbalanced genes.

Answer 16

True

Question 17

Define translocation and the two types of it.

Answer 17

Exchange of chromosome segments between two (usually) nonhomologous chromosomes.
Reciprocal translocation: exchange of DNA between Nonhomologous chromsomes
Robertsonian translocation: fusion of two acrocentric chromosomes.

Question 18

True or false: Translocations usually result in a balanced chromosome complement.

Answer 18

True

Question 19

Usual segregation of translocation chromosomes is in the ratio of __:__, but sometimes it can be __:__, which produces ____ (rarely) or _____.

Answer 19

2:1
3:1
Monosomy
Trisomy
3:1 segregation is seen in 5-20% of sperm (frequency depending on translocation present)

Question 20

Human Robertsonian translocations occur between which acrocentric chromosome?

Answer 20

13,14, 15, 21, 22

Question 21

Why is the loss of short arms in Robertsonian translocations tolerated?

Answer 21

Because most of the DNA in the short arms is redundant in the genome.

Question 22

What are the three most common Robertsonian translocations?

Answer 22

rob(13;14) ~33%
rob(14;21) ~30% (produces down syndrome)
rob(21;21) ~17% (aka an isosomal chromosome)

Question 23

True or false: During the combination of a normal gamete plus a gamete with a Robertsonian translocation, the chromosome number will be normal (46) and the genes will be balanced.

Answer 23

False: the chromosome number will be 45.

Question 24

What is a ring chromosome?

Answer 24

Loss of ends of chromosome and formation of ring (no telomeres)

Question 25

What is one defect caused by a ring chromosome?

Answer 25

r18 syndrome causes mental retardation, microcephaly, and hypertelorism.

XX,rX causes Turner syndrome

Question 26

What is an isochromosome?

Answer 26

One arm is missing and the other is duplicated, so the individual will be monosomic for the missing arm and trisomic for the duplicated arm (when you include the other gamete)

Question 27

True or false: isochromosomes can lead to a tetrasomy.

Answer 27

True: individual may have a normal chromosome complement plus an isochromosome, which produces tetrasomy for the region on the isochromosome (e.g. i(p18) syndrome: developmental delay, mild to severe mental retardation, microcephaly, high-arched palate)