Structural Chromosomal Abnormalities

Question 0

Three types of balanced structural abnormalities

Answer 0

Inversions
Reciprocal translocations
Robertsonian translocations

Question 1

Name and briefly describe the two primary types of structural abnormalities.

Answer 1

Balanced: normal complement of chromosomal material

Unbalanced: abnormal chromosomal content

Question 2

Four types of unbalanced structural abnormalities

Answer 2

Deletions
Duplications
Isochromosomes
Marker (ring) chromosomes

Question 3

What sort of DNA damage is required for all types of structural rearrangements?

Answer 3

Double strand breaks

Question 4

Define pericentric inversion

Answer 4

An inversion of a section of the chromosome which spans the centromere.
e.g. 46,XX,inv(5)(p12q14)
Note p and q present in the notation

Question 5

Consequences of gamete formation in carriers of pericentric inversions

Answer 5

Normal, balanced and unbalanced chromosomes may all result.

All are monocentric.

Question 6

Define paracentric inversions

Answer 6

An inversion of a section of the chromosome that does not span the centromere.
e.g. 46,XY,inv(3)(q22q24)
Note only q (or p) present in notation

Question 7

Consequences in gamete formation for carriers of paracentric inversions.

Answer 7

Normal, balanced and unbalanced chromosomes may all result.
Produces dicentric and acentric chromosomes, causing cell cycle arrest or apoptosis.
Paracentric inversions are more deleterious than pericentric.

Question 8

What unusual feature do peri and para centric inversions cause during meiosis?

Answer 8

Form chromosomal “loops” to align gene loci with homologous chromosomes. Recombinations in the looped regions lead to duplications and deletions of genes/centromeres.

Question 9

Define reciprocal translocation

Answer 9

The exchange of chromosomal regions between two non-homologous chromosomes. Also called derivatized (der).
Results in no loss of genetic information, carriers likely have normal phenotypes.

Question 10

What is the significance of chronic myelogenous leukemia in regards to chromosomal abnormalities?

Answer 10

It is one known occurrence of reciprocal translocation that causes disease in the carriers.
46,XX,t(9;22)(q34;q11.2)

Question 11

Define Robertsonian Translocation

Answer 11

The fusion of two acrocentric chromosomes at the centromere.

e.g. 45,XX,der(14;21)(q10;q10)

Question 12

How can a Robertsonian translocation lead to trisomy?

Answer 12

Fusion of two chromosomes (i.e. 14;21) leads to a single chromosome which may independently assort into a daughter cell along with the unfused homologue. (Trivalent segregation)

Question 13

What features must a chromosome possess to be stably transmissible through cell divisions?

Answer 13

Centromere
Telomeres
At least one replication origin

Question 14

Define “isochromosome”.

Answer 14

A chromosome in which one arm is missing and the other arm is duplicated in a mirror like fashion.

Question 15

What does a carrier of isochromosome 21 (21q21q) cause?

Answer 15

A carrier may have normal phenotype, but 100% of offspring will have trisomy 21 (Down syndrome).

Question 16

Name five mechanisms that can lead to Down syndrome.

Answer 16

Meiosis I non-disjunction (95% of cases) 47,XY,+21
Robertsonian translocation (4% of cases) 46,XX,der(14;21)+21
Isochromosome 21 46,XY,i(21)+21
Mosaic Down syndrome (non-disjunction in early zygotic division)
Partial Down syndrome (partial duplication of 21 genes)

Question 17

Define non-allelic homologous recombination (NAHR)

Answer 17

If alleles are not properly aligned during homologous recombination chromosomes will result with duplicated sequences on one and deleted sequences on the other. Unbalanced chromosomal rearrangements.

Question 18

How are Charcot-Marie-Tooth disease and Hereditary neuropathy to liability to pressure palsies related?

Answer 18

CMT disease is caused by the duplication (producing 3 copies) of the gene for peripheral myelinated protein-22, while HNPP is caused by the deletion (leaving 1 copy) of the same gene. 17p11.2

Question 19

How are Velocardialfacial syndrome and DiGeorge syndrome related?

Answer 19

Both are contiguous gene syndromes resulting from the a deletion at the same locus. (del 22q11)

Question 20

What percentage of miscarriages are due to chromosomal abnormalities?

Answer 20

50%

Question 21

What is the impact of repetitive patterns in DNA on chromosome structural integrity?

Answer 21

Repetitive patterns tend to cause deletions.

Question 22

What is the impact of repetitive patterns in DNA on chromosome structural integrity?

Answer 22

Repetitive patterns tend to cause deletions.

Question 23

What is contiguous gene syndrome?

Answer 23

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