Abnormalities of Chromosome Number Flashcards
chromosomes that have their centromere near the middle are called what?
metacentric chromosomes
chromosomes that have their centromere somewhat offset from the middle are called what?
submetacentric chromosomes
T or F. Both metacentric and submetacentric chromosomes have critical “single-copy” genes along their lengths, on both the p and q arms
T
What is an acrocentric chromosome?
Chromosomes with long (q) arms that contain critical “single-copy” genes (similar to other chromosomes), but also have short arms with specialized structures. In the microscope, acrocentric short arms can be recognized by their characteristic appearance with “stalks” and “satellites”
Which chromosome are acrocentric?
13, 14, 15, 21, 22
What do acrocentric short arms consist of?
1) repetitive sequences (similar sequences that are present in many copies). 2) all of our rRNA genes
What is the significance of the redundancy in rRNA gene copy number in acrocentric short arms?
a lot of variability is tolerated with absolutely no effect on phenotype
What are two examples of highly redundant sequences that can be quite variable with no phenotypic consequences?
rDNA and “noncentromeric heterochromatin” (typically located just under/adjacent to the centromere
Which are more common, number or structural chromosome abnormalities?
numerical Although relatively rare compared to numerical abnormalities, structural abnormalities are an important category of genetic disorders.
What is a balanced reciprocal translocation?
when two chromosomes exchange similar regions of their own chromosome with he other
What is a paracentric inversion?
When segments on the same arm of a chromosome switch positions (translocate)
What is a pericentric inversion?
When two segments on the same chromosome but not on the same arm exchange positions
Will a person with a balanced karyotype be expected to have a normal phenotype? If so, why is it worth noting?
Yes, they will be normal but they have a risk of passing an unbalanced karyotype to their children
What is different about an unbalanced karyotype from a balanced one?
an unbalanced karyotype (as a result of some type of structural abnormality) will have a net loss or gain or genetic material, while a balanced karyotype will not lose or gain genetic material during an exchange.Unbalanced karyotypes have a high risk of showing phenotypic abnormality
T or F. A reciprocal translocation involving the exchange of genetic material between two homologous chromosomes
F. It involves the exchange of genetic material between two NON-homologous chromosomes
Why can reciprocal translocations only occur between two q arms?
It doesn’t. Reciprocal translocations are random and can occur on either arm and on any chromosome
Are reciprocal translocations balanced or unbalanced?
Balanced. So the person who has it will be phenotypically normal, but they have risk of passing an unbalanced karyotype to offspring
what does this indicate:46,XY,t(2;15)
translation of chromosomes 2 and 15 on a male with 46 chromosomes
What is a simple translocation?
a reciprocal translocation where one of the breakpoints is very near a telomere
What is a Robertsonian translocation?
involves Long arm fusion of any two acrocentric chromosomes (i.e. the long arms fuse together and their associated short arms also fuse and are lost)NOTE: the fused long-arm chromosome has a single functional centromere
A balanced carrier of a Robertsonian translocation has a chromosome number of what?
45
Why is a Robertsonian translocation considered balanced?
Besides all of the critical genes are located on the long arms so no genetic material is lost during the fusionNOTE: the short arms consist entirely of redundant material, and the loss of this material is of no consequence
T or F. A Robertsonian translocation can occur on chromosome 17
False. They can only occur on acrocentric chromosomes (i.e. 13, 14, 15, 21, and 22)
what does this indicate:45,XY,der(14;21)
Robertsonian translocation- remember that the two p arms of each chromosome is lost during the fusion of two q arms
What is a Partial trisomy?
a structural abnormality that results in 3 copies of a particular chromosome segment
What is a Partial monosomy?
structural abnormality resulting in only one copy of a chromosome segment
T or F. Unbalanced structural abnormalities carry a high risk of abnormal phenotype
T
What is the difference between and interstitial deletion and a terminal deletion?
Interstitial deletion involves two breaks on one arm and the loss of a segment & rejoining of broken armsTerminal deletion involves a single break & loss of acentric terminal segment followed by the acquisition of new telomere (e.g. telomere healing)In either case, deletion gives rise to a partial monosomy
A condition where a person has one normal copy of chromosome 4 in addition to the one that is missing the tip of 4p would be called?
partial monosomyNOTE: This particular abnormality is seen often enough to constitute a syndrome called Wolf-Hirschhorn syndrome
partial trisomy is characterized by what?
A normal homolog and a homolog with two copies of a gene (added through a process called duplication)
Would a duplication (resulting in partial trisomy) be considered a balanced or unbalanced structural abnormality?
unbalanced
Are patients with chromosomal inversion (either paracentric or pericentric) considered balanced or unbalanced?
balanced (so they are phenotypically normal but carry reproductive risk- i.e. meiotic recombination within paired inversion loop may give rise to unbalanced gamete)
What is a isochromosome abnormality?
arises when a centromere splits in the wrong direction during cell division, separating the two short arm chromatids from the two long arm chromatids (so there are still two chromosomes but one has two q arms and the other has two p arms)NOTE: This is the only abnormality that does not involve incorrect repair of broken segments.
Is an isochromosome abnormality balanced or unbalanced?
unbalanced
Which is most likely to show phenotypic manifestation:1) large imbalances2) Robertsonian translocations3) small duplication4) inversion
Small duplicationRobertsonian translocations and inversions are balances and will not typically manifest phenotypically. Large imbalances will not be viable. Small duplications, on the other hand, are viable and will cause phenotypic issues (i.e. intellectual disability +/- developmental anomalies)
T or F. Some types of unbalanced structural abnormalities (interstitial deletions, duplications) are less likely to be inherited and more likely to have arisen de novo in the patient
T
What are some typical phenotypic consequences of unbalanced karyotypes?
Developmental delay (intellectual disability)Growth delayFacial dysmorphology & physical malformationsCongenital organ malformations, such as heart defects
Typically, is monosomy or trisomy more severe?
monosomy
T or F. Autosomal imbalance is less severe than sex chromosome imbalance
F. Sex chromosome imbalance is better tolerated (as long as viability requirements for the X chromosome are met)
What is something that typically helps moderate the effects of chromosome abnormality, whether it is structural or number?
mosaicism
What is the take-home message is that people who carry a balanced rearrangement?
They are expected to be phenotypically normal themselves, but they often are at risk to produce unbalanced gametes and, potentially, offspring with clinically significant problems.NOTE: all types of balanced rearrangement carry reproductive risks
Would someone who is 46,XY,t(8:9) be considered balanced or unbalanced?
balanced (reciprocal translocation)
Notes on Nature of risk of Reciprocal Translocations
Incidence of balanced translocation carriers ~1 in 500-1000 (normal phenotype)Often familialThree categories of gametes produced:Normal ® normal phenotypeBalanced ® normal phenotypeAbnormal / Unbalanced ® abnormal phenotype or miscarriage
