Clinical Cytogenics

Question 1

Chromosome analyses of bone marrow is performed to detect

Answer 1

the common abnormalities associated with a diagnosis of leukemia or lymphoma

Question 2

A common finding in childhood B-cell acute lymphoblastic leukemia (ALL) is _________ revealed by chromosome and FISH analyses

Answer 2

high hyper-diploidy

Question 3

t(9;22) is diagnostic for_________, which can be treated with tyrosine kinase inhibitors

Answer 3

chronic myelogenous leukemia (CML)

Question 4

t(9;22) is diagnostic for chronic myelogenous leukemia (CML), which can be treated with _________

Answer 4

tyrosine kinase inhibitors

Question 5

t(15;17) is diagnostic for a specific _________, which can be treated with retinoic acid

Answer 5

acute promyeloid leukemia (APML)

Question 6

t(15;17) is diagnostic for a specific acute promyeloid leukemia (APML), which can be treated with _________

Answer 6

retinoic acid

Question 7

FISH probe panels are used for

Answer 7

initial differential diagnosis, and as a means to monitor treatments or disease progression

Question 8

fluorescence-labeled probes

Answer 8

centromere
locus specific
fusion/dual fusion

Question 9

SNP chromosomal microarrays consist of

Answer 9

synthetic DNA oligomers ‘spotted’ onto a ‘platform’ (usually a specially treated, microscope slide called a bead chip) using robotic technologies

Question 10

CMA Methods

Answer 10

Sample—usually peripheral blood–DNA is amplified and labeled. After post hybridization washes, the arrays are viewed via an optical scanner, and a statistical test is performed for all the spots/color intensities for each probe, comparing to a population of 50 normal individuals’ DNA

Question 11

The SNP platform provides information on _________ and on _________, possibly revealing autosomal recessive conditions

Answer 11

intensity

runs of homozytosity

Question 12

The SNP platform provides information on intensity and on runs of homozygosity, possibly revealing _________

Answer 12

autosomal recessive conditions

Question 13

CMA testing frequently reveals _________ that cannot be seen by standard cytogenetics and light microscopy.

Answer 13

duplications or deletions of genetic material

Question 14

Copy number variants [CNVs]

Answer 14

There are over 35,000 definitive CNVs in our human population, and these are known to be heritable. Each normal individual carries ~10-20 CNVs. The size of the copy number variant may be 100’s of kilobases to megabase-pairs of genomic DNA.

Question 15

all human populations contain multiple genomic variants—that is

Answer 15

duplications or deletions within the DNA for which there is no phenotypic consequence. These cannot be detected at the chromosome level

Question 16

Test protocol (algorithm) used for

Answer 16

diagnosing infants, children, or adults with autism, cognitive disability, developmental delays, failure to thrive, dysmorphic features, seizures, and/or other multiple congenital anomalies (i.e. heart abnormalities)

Question 17

Test protocol used if- (4)

Answer 17

1. If deletion or duplication is detected by CMA consult DGV
2. Parental FISH studies will be offered to determine if this finding is a rare, normal, familial variant.
3. If a deletion or duplication is found in one or both parents, other family
   members may be tested by FISH. Often extensive consultation between
   the clinical geneticist, genetic counselors and cytogeneticist are required.
4. If the deletion or duplication is not found in either parent, and it is not found in
   the genomic variants Database, further data-base mining, literature
   searches are performed. Often a gene or genes mapped in the region of
   deletion or duplication reveals a syndromic association.

Question 18

centromere probe used for

Answer 18

Enumeration – leukemias

Question 19

Locus specific probe used for

Answer 19

Deletion–leukemias

Question 20

Fusion or Dual Fusion probe used for

Answer 20

Translocations-

leukemias