Chromosomal Abnormalities (Megee L2, 3) Flashcards
Give some examples of events that induce double strand breaks in the DNA
Ionizing radiation
Meiotic recombination
DNA repair mechanisms can induce double strand breaks
What has to happen (structurally) for a chromosomal rearrangement to take place?
two double strand breaks
List some results of DSB’s that occur during meiotic recombination
duplications deletions insertions inversions translocations
Where do the breakpoints of duplications, deletions, insertions, translocations and inversions all seem to occur?
Within regions of the chromosome composed of a lot of repeated sequences.
What are the two main categories of chromosomal structural rearrangements?
Balanced and Unbalanced
What is a balanced rearrangement?
Normal compliments of the genetic material but with varying stability during meiosis and mitosis
Give some examples of balanced rearrangements.
Inversion
Reciprocal Translocation
Robertsonian Translocation
Describe an inversion rearrangement.
Two double strand breaks on the same piece of DNA. The disconnected sequence is inverted before being reinserted and reconnected.
What is a paracentric inversion?
What is a pericentric inversion?
Paracentric: The removed, inverted and reinserted piece does NOT include the centromere.
Pericetric: The removed, inverted and reinserted piece DOES include the centromere.
Describe a reciprocal traslocation rearrangement.
Two non-homologous chromosomes basically each swap a piece of their DNA for a piece from the other chromosome. ex: 12345 12389 ----> 6789 6745
In pericentric inversions, crossovers within the inverted region can produce _________ and ________.
deletions and duplications.
In pericentric inversions, crossovers NOT within the inverted region will produce ____________ gametes.
balanced (full chromosomal compliment with the inversion)
In paracentric inversions, crossovers within the inverted region can produce _________ and ________.
dicentric and acentric
Individuals with balanced chromosomal rearrangements are “likely” to be ________.
phenotypically normal…but it really depends on the specific rearrangement
Suppose an individual has a reciprocal translocation in their chromosomes. At anaphase, a __________ figure is formed and segregation can be _______, _______ or ________.
quadravalent
alternative (normal or balanced)
adjacent 1 (unbalanced)
adjacent 2 (unbalanced)
Chronic myelogenous leukemia is caused by translocation of chromosomes ________ and _________
9 and 22 (q34;q11.2)
female
Describe a Robertsonian Translocation
Fusion of two acrocentric cromosomes within the centromeric regions.
What is lost during Robertsonian Translocation and why is this “O.K.”?
loss of the satellite and stalk DNA from the small arm of the original acrocentric chromosomes.
is “O.K.” because there is redundancy of the ribosomal DNA contained in the stalk region on the other acrocentric chromosomes.
What is the likely bad outcome of an individual with a Robertsonian Translocation?
It is likely that their offspring will have an abnormal kayrotype (monosomy and trisomy)
Which particular Robertsonian Translocation did Dr. Megee discuss in lecture?
a Robertsonian Translocation involving chromosome 21 can give rise to trisomy 21 in the individuals offspring.
What is an unbalanced structural chromosomal rearrangement?
the chromosome has additional or missing material
phenotypes are likely abnormal
List the various unbalanced strctural chromosomal rearrangements.
- Deletion
- Duplication
- Ring Chromosome
- Isochromosome
Describe a deletion unbalanced chromosome.
chromosome set has missing or additional genetic material
Chromosome ____ is most commonly involved in Robertsonian Translocation
14
Describe a terminal deletion.
When a deletion involved the end of a chromosome arm.
Describe an interstitial chromosomal deletion.
When the deletion is within a chromosomal arm.
Can result in acentric and/or a-telomeric fragments.
What is a ring chromosome and how is it produced?
An interstitial deletion can result in an acentric or centric fragment that forms a ring. The acentric ring is not stably transmissible.
What is an isochromosome?
A chromosome in which one arm is deleted and the other is duplicated in a mirror-image fashion.
Can result in monosomy and trisomy OR tetrachromosomy.
Trisomy of the mirrored arm and monosomy of the deleted arm. (there’s still one copy of that arm on the homologue)
OR
Tetrasomy when the isochromosome ins in addition to the two normal homologues.
What is the most common isochromosome?
The long arm of the X chromosome, i(Xq)
Appears in individuals with Turner Syndrome.
What is a dicentric chromosome?
When two chromosome segments, each with a centromere, fuse end to end.
Can be two different chromosomes or two chromatids of the same chromosome.
What is haploinsufficiency?
Inability of a single copy of the genetic material to carry out the functions normally performed by two copies.
Contiguous Gene syndrome is caused by…
Deletion of multiple contiguous genes; deletion due to abherent recombination between repetitive sequences.
What are some clinical findings that warrant investigation into possible sex chromosome abnormalities?
- delay in onset of puberty
- primary or secondary amenorrhea
- infertility
- ambiguous genitalia
Phenotypes associated with X and Y chromosomal defects are, in general, less severe than autosomal disorders because…
X inactivation and the small number of genes located on the Y chromosome
