Chromosomal Aberrations Flashcards
What is the percentage of chromosomal aberrations at birth? Pregnancies?
- 2%
0. 5%
What are the two main processes that generate structural chromosomal aberrations?
healing of DNA by double stranded breaks
unbalanced recombination
How does Cri-du-chat arise?
deletion on chromosome 5
What is DiGeorge syndrome also known as?
velocardiofacial syndrome
How does DiGeorge syndrome arise?
microdeletion on chromosome 22
What is the mode of inheritance for DiGeorge Syndrome?
autosomal dominant
Where does a translocation insert a chromosome? Insertion?
end of another chromosome
insertion = middle
What happens in a Robertsonian translocation?
long and short arms of a chromosome are exchanged
What is the most common chromosomal aberration in humans?
Robertsonian translocation
Which chromosomes are often involved in a Robertsonian translocation?
13q and 14q
What is an inversion?
chromosome suffers two breaks and is re-inserted in the wrong orientation
What is a balanced chromosomal rearrangment?
no change in the amount of genetic material
What can nondisjunction in meiosis lead to?
cells with surplus or missing chromosomes
What are the two processes that generate structural chromosomal aberrations?
non-homologous end joining and
What is more severe, deletions or duplications?
deletions
How does Cru du Chat arise?
deletion on chromosome 5
How does diGeorge syndrome arise?
microdeletion on chromosome 22
What is DiGeorge syndrome also known as?
velocardiofacial syndrome
What is the most common phenotype of DiGeorge syndrome?
congenital heart defect
Where does an insertion move a chromosome?
into the middle of another chromosome
What does a translocation move a chromosome?
attaches it to the end
How is the Philadelphia Chromosome generated?
a translocation between chromosome 9 and 22
Regarding the Philadelphia Chromosome, what specific genes are traslocated?
ABL tyrosine kinase from 9 to the BCR region on 22
What is a Robertsonian translocation?
long and short arm of two chromosomes are exchanged
What is the most common chromosomal rearrangement?
Robertsonian Translocation of 13q and 14q
What is an inversion?
when a chromosome suffers two breaks and the broken-off fragment is re-inserted into the wrong direction
What happens when an inverted chromosome pairs with its homolog during meiosis?
an inversion loop is created
Regarding a Robertsonian Translocation, what usually happens to the short arm containing chromosome?
it gets lost
Regarding the philadelphia chromosome, what gene moves to what chromosome?
ABL from 9 moves to BCR of 22
A robertsonian translocation often involves which two chromosomes?
13q and 14q
What will an inverted chromosome form in meiosis?
inversion loop
Regarding an inversion loop, what can meiosis create?
a dicentric or acentric chromosome
When do patients usually become aware of their balanced translocation?
reproduction
What cells is most frequently used to perform karyotypes?
lymphocytes
What cell cycle phase are chromosomes arrested in during karyotyping?
metaphase
Where does methylation of DNA occur?
on cytosine residues in CpG islands
What protein is responsible for introducing de novo methylation of DNA?
DNMT 3a and 3b
What protein is defective in Rett Syndrome?
methyl cytosine binding protein
What characteristic of DNA is lost during Rett Syndrome?
Loss of txn silencing
How is Rett Disease transmitted?
X-linked dominant
Where does the silencing of histones occur via acetylation?
tail
In addition to acetylation, what are three other modifications of histones?
phosphorylation, ubiquitination and methylation
What protein binds methylated histones?
HP1
What happens to histones after they are deacetylated?
they become methylated
What do HP1 proteins bind?
histone methylase
What are MBPs?
methylcytosine binding proteins
What is the function of imprinting?
to silence chromosomal regions by DNA methylation
What signals an end to histone methylation?
a boundary element
How does methylation of cytosine proceed?
it is self propogating
What role is imparted by imprinting?
mark a chromosome as maternal or paternal in origin
When is an inversion loop formed?
during meiosis
