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Flashcards in Constitutional Cytogenetics Deck (21)
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Name some indications for constitutional cytogenetic studies.

1. Prenatal diagnosis (eg trisomies)
2. Postnatal diagnosis (abnormalities of development)
3. Recurrent infertility or miscarriages


What specimens are suitable for constitutional cytogenetic studies?

Prenatal: Amniotic fluid, chorionic villi, maternal blood
POC: Fetal tissue, chorionic villi, FFPE blocks (FISH-only)
Recurrent pregnancy loss: Peripheral blood


What mitogens are used to culture T cells? B cells?

T-cells: Phytohemagglutinin (PHA)
B-cells: Pokeweed extract


What method of banding is used in the US? What does it stain? What resolution does it confer?

G-banding; stains AT-rich regions (gene-poor heterochromatin) darkly to a resolution of 5-10 Mb


What is C banding?

Staining of constitutive heterochromatin, for example all centromeres and the heterochromatic region of Y


What is NOR staining?

Staining of the "Nucleolar Organizer Regions"; essentially rRNA that is present on satellite stalks.


What are acrocentric chromosomes? Which are they?

Acrocentric chromosomes only have one arm; the other comprised of "stalks" of rRNA which form the nucleolus?

13/14/15, 21/22


What does Aneuvision detect?

Copy numbers of chromosomes 13, 18, 21, X, and Y.


A prenatal specimen appears to demonstrate trisomy 21. What could this represent if not a true diagnosis?

Contamination by normal maternal cells, confined placental mosaicism, or chimerism.


What are the general turn-around times for karyotypes for: Bloods, prenatal samples, and POCs/skins?

What about for FISH?

Bloods: 28d (7d if STAT)
Prenatals: 14d
POCs / Skin biopsies: 42d

FISH: 7-10d


Order the most common constitutional trisomies / monosomies by their relative frequency.

+21 > XXY/XYY/XXX > XO > +18 > +21


Which chromosomes are parentally silenced?

6 (paternal)
7 (maternal)
11 (both)
14 (both)
15 (both)
20 (both)


Recall which form of uniparental disomy results in the following diseases:
- Beckwith-Wiedemann syndrome
- Prader-Willi syndrome
- Angelman syndrome

BWS: Paternal 11
PWS: Paternal 15
Angelman: Maternal 15


Recall which form of uniparental disomy results in the following diseases:
- Transient neonatal diabetes
- Pseudohypoparathyroidism
- Silver-Russell syndrome

Transient neonatal DM: Paternal 6
Pseudohypoparathyroidism: Paternal 20
Silver-Russell: Maternal 7 or 11


What is a ring chromosome?

What is a dicentric chromosome?

What is a double minute chromosome?

Ring: Loss of telomeres with fusion of each end.

Dicentric: A chromosome with two centromeres.

Double minute: Fragments of extrachromosomal DNA, mostly seen in tumors and conferring drug resistance.


What is a robertsonian translocation?

Fusion of two acrocentric chromosomes resulting in one large metacentric or submetacentric chromosome.


What is the difference between a pericentric and paracentric inversion?

Paricentric inversions involve the centromere, whereas paracentric inversions are limited to one arm.


What is an isochromosome and how does it form?

Isochromosomes are structural rearrangements resulting from mis-division of the centromere, resulting in mirror long and short arms.


What is normally responsible for X-chromosome inactivation?

The XIST gene, which is itself on the X chromosome, promotes trimethylation of histone H3 at Lysine 27.


How may small deletions (eg < 5 Mb) be detected?

FISH or SNP microarray analysis.


Challenge: Recall the deleted regions in the following diseases.
1. TAR syndrome
2. SOTOS syndrome
4. Smith-Magenis syndrome

1. 1q21
2. 5q35
3. 17p12
4. 17p11.2