2F- Clinical Cytogenetics Flashcards
What is a karyotype?
refers to the number and type of chromosomes present in an individual
What phase of mitosis are chromosomes are maximally condensed and easiest to see?
Metaphase
What is the term when the p and q arms are of equal length?
Metacentric
What is the term when the p arm is smaller than the q arm?
Submetacentric
What is the term when the p arm contains no genetic information and just contains a stalk and satellite?
Acrocentric
What is a telomere?
The tip of each chromosome that is repetitive and protects the chromosome from degradation.
What is a satellite?
seen with an acrocentric chromosome, the short arm (p arm) may just be a little nubbin, which is called a satellite which is connected to the chromosome by a stalk.
What is banding?
Chromosome banding helps greatly in the detection of deletions, duplications, and other structural abnormalities, and it facilitates the correct identification of individual chromosomes
What is G-banding?
Most common staining technique used. Giemsa stain is applied after the chromosomal proteins are partially digested by trypsin
What is R-banding?
best for staining the Distal Ends of the chromosomes, it requires heat treatment and reverses the usual white and black pattern that is seen in G-bands and Q-bands
What is Q-banding?
early method that requires fluorescent microscope, not used much now
What is C-banding?
stains the constitutive heterochromatin, which usually lies near the centromere
What is constitutive heterochromatin?
heterochromatin that is found near the centromere and is stained with C-banding.
What is high resolution banding?
chromosome staining during prophase or early metaphase (prometaphase), before max condensation and when they are more extended. This increases the number of bands observable to about 300 to 450 to as many as 800.
What is cool about high resolution banding?
This allows the detection of less obvious abnormalities usually not seen with conventional banding.
What is the goal of FISH?
You use a piece of DNA what will only bind to a certain known area of the chromosome, the DNA you are using will fluoresce indicating that it did bind to the chromosome where it was supposed to.
What is FISH used for?
to detect deletions (normal pt’s will have fluorescent probe attach, if deleted then it doesnt attach)
What if you see more glowing pieces than you should?
There is a duplication of the gene targeted by the probe (or it could be a trisomy)
What is spectral karyotyping?
you use varying combinations of five different fluorescent probes so that each chromosome is uniquely colored, which is useful for identifying small chromosome rearrangements
What is comparative genomic hybridization used for?
detect losses or duplications of whole chromosomes or specific chromosome regions
What is the comparative genomic hybridization procedure?
label normal DNA one color and label cancer cell DNA another color, and put them in a metaphase preparation and see which hybridizes, you then measure the color to detect loss or gain of material
In CGH, if there is a deletion in the mutant chromosome, what color will show?
The color used to label the normal DNA will show.
In CGH, if there is a duplication in the mutant chromosome, what color will show?
the color used to label the abnormal DNA will show
Why is CGH better than FISH?
highly automated, requiring less time from laboratory personnel. There is no need for dividing cells, and a minute amount of DNA is sufficient for analysis of the entire genome
Why is CGH worse than FISH?
cannot detect balanced rearrangements (reciprocal translocations or inversions.)
What is euploidy?
a cell that contains a multiple of 23 chromosomes
What is polyploidy?
cell that contains a multiple of 23 chromosomes greater than 46
What is triploidy?
nucleus with 69 chromosomes
What is the cause of triploidy?
usually caused by egg being fertilized by two sperm (dispermy)
What is the cause of tetraploidy (92 chromosomes)?
mitotic failure
What is aneuploidy?
Cells that contain missing or additional individual chromosomes
Why is trisomy more common than monsomies?
the cell can deal with excess material much better than a deficit
What is the most common cause of aneuploidy?
Non-Disjunction. It’s the failure of chromosomes to disjoin normally during meiosis.
Give the Dx with the following karyotype: 47,XY,+21
Male with trisomy 21 (Down’s Syndrome)
What are some of the features of down’s syndrome?
mental retardation, low nasal root, skin redundant at nape of neck, flat occiput, simian crease on palms, muscular hypotonia, males and 1/2 of females are sterile.
What are some significant medical problems for trisomy 21?
significant medical problem is structural heart defects, especially an atrioventricular (AV) canal and ventral septal defect
What is the survival rate of trisomy 21?
80% make it to 10 y/o, 50% to 50
What is the most common causes of trisomy 21?
nondisjunctions and translocations
What can mosaicism do to trisomy 21?
Mosaicism is when someone has a normal set of chromosomes in some cells and abnormal in other cells. This leads to a lesser effect of the abnormality, for example mosaicism in Downs leads to less mental retardation.
Give the Dx with the following karyotype: 47,XX,+18
female trisomy 18 (Edwards syndrome)
What are some physical features of Edwards syndrome?
prenatal growth deficiency (weight that is low for gestational age), distinctive hand abnormality, small ears with unraveled helices, a small mouth, a short sternum, and short halluces (first toes).
What are some risk factors for trisomy 18?
VSD’s of the heart, omphalocele, radial aplasia, spina bifida and diaphragmatic hernias
What is the survival rate of trisomy 18?
very low. 50% die within weeks of birth, 5% make it to year 1
Give the Dx with the following karyotype: 47,XX,+13
Female trisomy 13 (patau syndrome)
What are some physical features of patau syndrome?
Oral-facial clefts, microphthalmia (small, abnormally formed eyes), and postaxial polydactyly
What are some risk factors for trisomy 13?
Malformations of the central nervous system are often seen, as are heart defects and renal abnormalities. Cutis aplasia (a scalp defect on the posterior occiput)
What is the survival rate of trisomy 13?
Low, 95% die before the age of 1
Give the Dx with the following karyotype: 45,XO
Female with Turners syndrome
What are some physical features of Turners syndrome?
(1) Always female with short stature, sexual infantilism and ovarian dysgenesis
(2) Also a shield-like chest, triangle-shaped face; posteriorly rotated external ears; and a broad, “webbed neck”, and lymphedema of the hands and feet
What are some risk factors for Turners?
(1) Most common are heart defects (bicuspid aortic valve in 50% of patients and coarctation/narrowing of the aorta). Kidney problems also common.
(2) Streak ovaries causing sterility
(3) Majority of cases are due to lack of paternal sex chromosome
Give the Dx with the following karyotype: 47, XXY
Klinefelter syndrome
What are some physical features of Klinefelter syndrome?
(1) Taller than average, with disproportionately long arms and legs, gynecomastia, and small testes leading to sterility.
(2) Little body hair and small muscle mass. Learning disabilities with IQ about 10 points lower than average.
Gynecomastia
Give the Dx with the following karyotype: 47, XXX
Woman with extra X (some places call it the “superwoman” syndrome)
What are some physical features of XXX?
Usually benign consequences with rare overt physical abnormalities. May suffer from sterility, menstrual irregularity, or mild mental retardation.
What are some physical features of XYY?
Always male, and are taller than average, and they have a 10 to 15 point reduction in average IQ, but usually no physical problems.
What is an unbalanced rearrangement?
the rearrangement causes a gain or loss of chromosomal material
What is an inversion?
the result of two breaks on a chromosome followed by the reinsertion of the intervening fragment at its original site but in inverted order
What is a pericentric inversion?
inversion includes centromere
What is a paracentric inversion?
inversion does not include centromere
What is a isochromosome?
hromosome divides along the axis perpendicular to its usual axis of division, results in a chromosome that has two copies of one arm and no copies of the other.
What is a translocation?
interchange of genetic material between nonhomologous chromosomes
What is a reciprocal translocation?
happen when breaks occur in two different chromosomes and the material is mutually exchanged
What is a Robertsonian translocation?
the short arms of two nonhomologous chromosomes are lost and the long arms fuse at the centromere to form a single chromosome
Where do Robertsonian translocations typically occur?
only occurs in acrocentric chromosomes (13, 14, 15, 21, 22) and usually its 14 and 21
What is a deletion?
caused by a chromosome break and subsequent loss of genetic material.
What is a terminal deletion?
single break leading to a loss that includes the chromosome’s tip
What is an insertional deletion?
two breaks occur and the material between the breaks is lost
What is a ring chromosome?
occurs after both tips of a chromosome are deleted, and the resulting chromosomes ends will fuse forming a ring. Usually lost resulting in a monosomy.
What are duplications?
occurs when part of a chromosome is copied (duplicated) abnormally, resulting in extra genetic material from the duplicated segment.
What causes duplications?
arise from unequal crossover, or they can occur among the offspring of reciprocal translocation carriers
What is uniparental disomy?
one parent has contributed two copies of a chromosome and the other parent has contributed no copies
What is isodiomy?
the parent has contributed two copies of one homolog
What is heterodisomy?
the parent has contributed one copy of each homolog
What are the causes of Williams syndrome?
microdeletion syndrome. In this syndrome, individual genes have been identified with different defects, and the defect present depends on what gene(s) is deleted.
What are the clinical manifestations of Williams syndrome?
mental retardation, supravalvular aortic stenosis (SVAS), multiple peripheral pulmonary arterial stenoses, dental malformations, and hypercalcemia
What is WAGR syndrome?
A microdeletion syndrome similar to Williams in that it depends on what gene(s) is/are deleted. The more genes that are deleted the more defects present.
What are the clinical manifestations of WAGR syndrome?
Wilms tumor (a kidney tumor), aniridia (absence of the iris), genitourinary abnormalities, and mental retardation
What is the cause of chronic myelogenous leukemia (CML)?
CML is caused by a reciprocal translocation between C9 and C22, leading to a small C22 and a large C9
What are the clinical manifestations of CML?
increased tyrosine kinase activity leads to malignancy in hematopoietic cells, drugs can inhibit this tyrosine kinase.
What is the cause of Burkitt’s lymphoma?
reciprocal translocation between C8 and C14.
In burkitt’s lymphoma, after the translocation MYC is moved from 8q to 14q, what happens?
MYC is transcribed, which now causes malignancy
