Chromosome Structural Abnormalities Flashcards
Pallister Killian syndrome is caused by ?
Isochromosome 12p (tetrasomy 12p mosaicism)
_______ rearrangements/breakpoints occur in unrelated families
Recurrent
__________rearrangements/breakpoints occur in families
random
The ___________ is the first person in the family to have the rearrangement (balanced or unbalanced)
proband
Of all rearrangements, ______________ are the most common
translocations (txl)
________% of the population has a translocation
0.1% (to 0.14%)
Balanced de novo translocations have a ______% risk of symptoms
6-9%
Balanced de novo translocations (1 in 500) occur in meiosis ___________ of _____________ (gamete)
meiosis I
sperm
Three tests for translocations
karyotype (3-5 MB)
FISH
CMA (200 KB to 20 KB)
Chromosomes for Robertsonian translocations
13, 14, 15, 21, 22 and Y
There are two types of translocations.
1. ____________ in which two ends of chromosomes exchange segments.
2. ____________ exchange of p arms of acrocentric chromosomes.
- Reciprocal
- Robertsonian
___________ structure is where the homologs of the translocated chromosomes all try to pair in meiosis I
Tetravalent
In translocations and quadrivalent structures during meiosis I, __________ segregation leads to balanced chromosomes while ______________ segregation leads to unbalanced chromosomes
alternate
adjacent
First recognized recurrent translocation in humans
t(11;22)(q23.3;q11.2) -
47 chroms, 3:1 segregation = Emmanuel syndrome
t(11;22)(q23.3;q11.2) with 3:1 segregation (Chr 11, Chr 22, der(22))
Emmanuel syndrome
Emmanuel syndrome phenotype
ID
Heart defects
Failure to thrive
Malformations
Two types of inversions
- Pericentric (with centromere)
- Paracentric (same chromosome arm)
A _________ inversion involves the centromere
Pericentric
Pericentric inversions occur in ____________
meiosis I
Risk of having viable unbalanced embryo with pericentric inversion: ______ to ______%
5-15%
Chromosomes which tolerate pericentric inversion
13, 18, 21
Name for syndrome with pericentric, inv(8)(p23.1q22.1)?
rec(8)dup(8q)inv(8)(p23.1q22.1)
San Luis Valley syndrome
Dup(q)/Del(p)
San Luis Valley syndrome phenotype?
*Heart defects
Tetralogy of Fallot, conotruncal defects, septal defects
*Dysmorphic facial features
Hypertelorism, abnormal dentition, abnormal hair whorl, wide face
*Intellectual disability
Paracentric inversions have a risk of livebirth with recombinant of 0.1-0.5% due to ___________ segregation and recombination issues
meiosis I (U-loop better than than classic inversion loop crossover)
Ring chromosomes usually occur__ _______ and are supernumerary chromosomes (47) but can be stable and inherited
de novo
Ring chromosome phenotype (generic)
Growth restriction
Mild-Moderate Intellectual Disabilities
Minor dysmorphic features
Infertility
Ring chromosome formation mechanism
Both ends of chromosome are deleted
Incidence of ring chromosomes in live birth
1 in 30,000-60,000
Isochromosomes form with loss of 2p arms and formation of two linked q arms. Name two examples.
- Pallister Killian (mosaic 12p tetrasomy)
- Variant Turner syndrome (Xq)
_____% of protein-coding genes are dosage sensitive (haploinsufficient or triplosensistive)
17%
Most reciprocal translocations, inversions, rings, etc. are unique (__________) to the proband/family in which it was found
random
The mechanism for rearrangements involves _________ sequences
repetitive
(Alu, LINES, SINES, low copy repeats, dups etc.)
______________ is the mechanism underlying most RECURRENT structural rearrangements
NAHR = non-allelic homologous recombination (repetitive sequences between genes)
______________ is the mechanism underlying most NON-RECURRENT structural rearrangements
Non-homologous end joining (NHEJ)
*method for repairing double strands breaks
