Chromosomal Abnormalities II

Question 1

What are the 3 types of balanced chromosomal rearrangements?

Answer 1

Inversion, reciprocal translocation, robersonian translocation

Question 2

Describe an inversion

Answer 2

2x DSB, sequence in-between is flipped (think of a crossover occurring between steps of a hairpin).
Pericentric = includes centromere
Paracentric = excludes centromere
Individual may be fine, but gametes may mess up due to formation of loop structure

Question 3

Describe a reciprocal translocation

Answer 3

Breakage and rejoining of NON-homologous chromosomes
1–2–3–4 —-> 1–2–7–8
5–6–7–8 —-> 5–6–3–4
During gametogenesis, chromosomes pair and form a quadrivalent figure; separated 1 of 3 ways. Alternate = balanced. Adjacent-1 or -2 = unbalanced

Question 4

Describe a Robertsonian translocation

Answer 4

2 acrocentric chromosomes fuse @ centromeric regions –> loss of both short arms (which contain rDNA repeats).
During gametogenesis, chromosomes pair and form a trivalent figure; again this can be balanced or unbalanced

Question 5

What are 4 types of unbalanced chromosomal rearrangements?

Answer 5

Deletion (terminal or interstitial) - can loop out
Duplication: same chromosome overlaps incorrectly.
–1–2–3–4 –> –1–4
–1–2–3–4 –> –1–2–3–2–3–4
Ring chromosome
Isochromosome: one arm is missing and the other diplicates in a mirror-like fashion (100% abnormal gametes - mono- or tri- somy)

Question 6

Most chromosome structural abnormalities found in fetuses and newborns that are associated with serious clinical effects are attributable to __________. They are therefore ________ to occur again.

Answer 6

random event; unlikely

Question 7

Occasionally a serious chromosomal abnormality can be inherited from a seemingly normal parent who carries a _________ chromosomal abnormality such as a ___________. In these rare cases, the recurrence risk could be much _________ (e.g. isochromosome 21, where the recurrence risk is ______!).

Answer 7

balanced; translocation; increased; 100%

Question 8

It is necessary to ___________ to exclude the possibility of an inherited abnormality, before counseling patients about recurrence risk.

Answer 8

examine the chromosomes of parents cytologically

Question 9

Describe Charcot Marie Tooth

Answer 9

• Characterized by weakness of the feet and lower leg muscles (hammertoes), then weakness / muscle atrophy of the hands later
• several forms of CMT exist; all affect the normal function of peripheral nerves
• CMT type 1A is an autosomal dominant disorder caused by a DUPLICATION of the gene for peripheral myelin protein-22 (PMP-22)

Question 10

How is Charcot Marie Tooth different from Hereditary Neuropathy with predisposition to pressure palsy (HNPP)

Answer 10

HNPP is a DELETION of the gene for peripheral myelin protein-22 (PMP-22)
Basically, CMT1A results from having an extra copy of PMP22, HNPP results from the loss of a copy of PMP22.
No muscle weakness; pt gets excessive tingling/sleep feeling for months

Question 11

Compare & contrast DiGeorge & Velocardiofacial syndromes

Answer 11

Both result from a deletion on 22q11.
Velocardio = cleft palate, facial (lateral nasal buildup) and cardiac septal defects
DiGeorge = absent or hypoplastic thymus and parathyroids, congenital heart disease

Question 12

In Adjecent-1, homologous centromeres go to _____ cells.

Answer 12

different
in adjacent 1 segregation, homologous centromeres go to different daughter cells

In adjacent 2 segregation both homologs go to the same daughter cell. It will never produce a balanced karyotype