Translocations Flashcards
Translocations can allow for up to ___% of the genome to be trisomic (depending on the region)
4%
Translocations can allow for up to ___% of the genome to be monosomic (depending on the region)
2%
In translocations it is always recommended to study the ________ chromosomes
parental
Frequency of Robertsonian translocations
1 in 800/1000 (part of the balanced 1in 500 risk)
Acrocentric p arms account for _____ % of the genome
2.2%
Acrocentric chromosome distal satellite p13 arms contain up to 300 copies of _______ genes responsible for organizing the nucleolus
rRNA
Acrocentric chromosome distal satellite p12 region is known as the _________ ______ and comes before the p13 rRNA region
satellite stalk
5 acrocentric chromosomes
13, 14, 15, 21 and 22
_______ satellite family at centromeres of 1, 9, 13, 14, 15, 21, 22 and Y
beta
A ________ translocation (1916) involves two acrocentric chromosomes at the centromere where the derivative p arms are largely lost and two copies of q arms are observed
Robersonian
_____ - _____ % of trisomy 21 are Robertsonian translocations
4-5%
Derivative 21 mostly involve D chromosomes ____, _____ and _____ as the G chromosomes ______ and _____ are not viable
D = 13, 14, 15
G = 21 and 22
Most (75%) Robertsonian translocations involving 13, 14 and 15 are _____ ______ but up to 25% can be _______
de novo -75%
familial - 25%
Segregation of Robertsonian translocations occurs in meiosis ______ and involves the trivalent formation
metaphase I
Adjacent or alternate segregation patterns result in normal and balanced translocations?
Alternate
Almost all DS inherited from a familial der(14;21) is _______ (paternal/maternal) in
origin from error in meiosis ________
maternal, meiosis I
der(14;21) carriers
Risk of fetus with translocation trisomy 21,
− maternal carrier _____% at amniocentesis, about _______% at term
15%
10-12%
der(14;21) carriers
Risk of fetus with translocation trisomy 21,
− Paternal carrier, <____%
<1%
der(14;21) carriers
Risk of UPD14?
<1/2% for both maternal and paternal
True or false? The rare der(21;21) carrier or isochromosome 21q has essentially no chance of a chromosomally normal conception.
True
The rare der(21;21) carrier or isochromosome 21q is mechanistically the result of an error in meiosis _________?
meiosis I
Trisomy 13 incidence in live births?
1 in 16,000
Trisomy 13 life expectancy?
1 year
Trisomy 13 phenotype?
heart defects
urinary malformations
* Dysmorphia:
- Polydactyly; clenched fist
- Small head and eyes
- Cleft lip/palate
- Rocker-bottom feet
– Holoprosencephally
Most common (1 in 1300) chromosome structural rearrangement?
der (13;14)
rob (13;14)
Incidence of rob/der (13;14)
1 in 1300
Der (13;14) is _______% of all Robertsonian translocations
75%
Maternal vs paternal risk of der (13;14) having offspring with unbalanced
karyotypes?
Maternal: 1%
Paternal: <1%
There is an ___________risk of Robertsonian translocations in infertile men
increased
Risk of UPD in der (13;14) translocations?
<1/2%
der (14;15) prevalence?
der (13;15) prevalence?
der(15;15) prevalence?
der (14;15) = 5%
der (13;15) = 2%
der(15;15) = 2%
Whenever chromosome ______ is involved in a Robertsonian translocation, parental chromosomes are recommended?
15
Mechanism of der(15;15)?
Fusion in zygote at mitosis
der (13;15) UPD with trisomy rescue mechanism?
Trisomy 15 with adjacent segregation followed by rescue by postzygotic loss of 15 (usually 15 UPD maternal)
der (13;15) with residual trisomy?
Mosaic mitotic loss of trisomy 15 but usually with severe PWS phenotype
Loss of paternal 15q11.2-q13?
Prader Willi Syndrome (20-30% UPDmat)
Loss of maternal 15q11.2-q13?
Angelman syndrome (7% UPDpat)
The most common recurrent non-Robertsonian translocation in humans ?
t(11;22)(q23;q11.2)
The majority of t(11;22) are _________ (99%)
familial
Risk in t(11;22) for SAB (maternal = paternal)
> 27%
Risk in t(11;22) for liveborn with derivative: ____% mat, ___% pat
5%, maternal, 2-5% paternal
Risk in t(11;22) for offspring to be balanced carrier maternal and paternal
maternal 55%
paternal 40%
t(11;22) involves a _______ at 22q11.2 and an ______-rich region on 11q23
LCR on 22q11.2
AT-rich on 11q23
PATRR = Palindromic AT-rich repeats form ______ _______
hairpin loops
Deletions, duplications and translocations at 22q11 occur in greater than _______ live births
1/3000 – 4000
The 22q11 region is a hotspot for _________ chromosomal rearrangements
nonrandom
The 22q11 deletion syndrome includes
– DiGeorge,
– Velocardiofacial
– Conotruncal anomaly face syndromes
22q duplications include
Cat Eye syndrome
* Supernumerary derivative chromosome 22
Emanuel syndrome
* duplication of 22q10-22q11 and duplication of 11q23-qter
on a supernumerary derivative chromosome 22
Supernumerary +der(22)t(11;22)
Emanuel syndrome
Supernumerary +der(22)t(11;22) phenotypes
conotruncal heart defects (cardiac outflow tract anomalies)
microcephaly
cleft palate
micrognathia
skin tags or pits
genital abnormalities in males
intellectual disability
* Features of both 11q trisomy (e.g. microcephaly) and trisomy 22
(e.g. imperforate anus
