Chromosome Structural Abnormalities

Question 1

Pallister Killian syndrome is caused by ?

Answer 1

Isochromosome 12p (tetrasomy 12p mosaicism)

Question 2

_______ rearrangements/breakpoints occur in unrelated families

Answer 2

Recurrent

Question 3

__________rearrangements/breakpoints occur in families

Answer 3

random

Question 4

The ___________ is the first person in the family to have the rearrangement (balanced or unbalanced)

Answer 4

proband

Question 5

Of all rearrangements, ______________ are the most common

Answer 5

translocations (txl)

Question 6

________% of the population has a translocation

Answer 6

0.1% (to 0.14%)

Question 7

Balanced de novo translocations have a ______% risk of symptoms

Answer 7

6-9%

Question 8

Balanced de novo translocations (1 in 500) occur in meiosis ___________ of _____________ (gamete)

Answer 8

meiosis I
sperm

Question 9

Three tests for translocations

Answer 9

karyotype (3-5 MB)
FISH
CMA (200 KB to 20 KB)

Question 10

Chromosomes for Robertsonian translocations

Answer 10

13, 14, 15, 21, 22 and Y

Question 11

There are two types of translocations.
1. ____________ in which two ends of chromosomes exchange segments.
2. ____________ exchange of p arms of acrocentric chromosomes.

Answer 11

1. Reciprocal
2. Robertsonian

Question 12

___________ structure is where the homologs of the translocated chromosomes all try to pair in meiosis I

Answer 12

Tetravalent

Question 13

In translocations and quadrivalent structures during meiosis I, __________ segregation leads to balanced chromosomes while ______________ segregation leads to unbalanced chromosomes

Answer 13

alternate
adjacent

Question 14

First recognized recurrent translocation in humans

Answer 14

t(11;22)(q23.3;q11.2) -

47 chroms, 3:1 segregation = Emmanuel syndrome

Question 15

t(11;22)(q23.3;q11.2) with 3:1 segregation (Chr 11, Chr 22, der(22))

Answer 15

Emmanuel syndrome

Question 16

Emmanuel syndrome phenotype

Answer 16

ID
Heart defects
Failure to thrive
Malformations

Question 17

Two types of inversions

Answer 17

1. Pericentric (with centromere)
2. Paracentric (same chromosome arm)

Question 18

A _________ inversion involves the centromere

Answer 18

Pericentric

Question 19

Pericentric inversions occur in ____________

Answer 19

meiosis I

Question 20

Risk of having viable unbalanced embryo with pericentric inversion: ______ to ______%

Answer 20

5-15%

Question 21

Chromosomes which tolerate pericentric inversion

Answer 21

13, 18, 21

Question 21

Name for syndrome with pericentric, inv(8)(p23.1q22.1)?
rec(8)dup(8q)inv(8)(p23.1q22.1)

Answer 21

San Luis Valley syndrome
Dup(q)/Del(p)

Question 22

San Luis Valley syndrome phenotype?

Answer 22

*Heart defects
Tetralogy of Fallot, conotruncal defects, septal defects
*Dysmorphic facial features
Hypertelorism, abnormal dentition, abnormal hair whorl, wide face
*Intellectual disability

Question 23

Paracentric inversions have a risk of livebirth with recombinant of 0.1-0.5% due to ___________ segregation and recombination issues

Answer 23

meiosis I (U-loop better than than classic inversion loop crossover)

Question 24

Ring chromosomes usually occur__ _______ and are supernumerary chromosomes (47) but can be stable and inherited

Answer 24

de novo

Question 25

Ring chromosome phenotype (generic)

Answer 25

Growth restriction
Mild-Moderate Intellectual Disabilities
Minor dysmorphic features
Infertility

Question 26

Ring chromosome formation mechanism

Answer 26

Both ends of chromosome are deleted

Question 27

Incidence of ring chromosomes in live birth

Answer 27

1 in 30,000-60,000

Question 28

Isochromosomes form with loss of 2p arms and formation of two linked q arms. Name two examples.

Answer 28

1. Pallister Killian (mosaic 12p tetrasomy)
2. Variant Turner syndrome (Xq)

Question 29

_____% of protein-coding genes are dosage sensitive (haploinsufficient or triplosensistive)

Answer 29

17%

Question 30

Most reciprocal translocations, inversions, rings, etc. are unique (__________) to the proband/family in which it was found

Answer 30

random

Question 31

The mechanism for rearrangements involves _________ sequences

Answer 31

repetitive
(Alu, LINES, SINES, low copy repeats, dups etc.)

Question 32

______________ is the mechanism underlying most RECURRENT structural rearrangements

Answer 32

NAHR = non-allelic homologous recombination (repetitive sequences between genes)

Question 33

______________ is the mechanism underlying most NON-RECURRENT structural rearrangements

Answer 33

Non-homologous end joining (NHEJ)
*method for repairing double strands breaks