Clinical Cytogenics Flashcards
Chromosome analyses of bone marrow is performed to detect
the common abnormalities associated with a diagnosis of leukemia or lymphoma
A common finding in childhood B-cell acute lymphoblastic leukemia (ALL) is _________ revealed by chromosome and FISH analyses
high hyper-diploidy
t(9;22) is diagnostic for_________, which can be treated with tyrosine kinase inhibitors
chronic myelogenous leukemia (CML)
t(9;22) is diagnostic for chronic myelogenous leukemia (CML), which can be treated with _________
tyrosine kinase inhibitors
t(15;17) is diagnostic for a specific _________, which can be treated with retinoic acid
acute promyeloid leukemia (APML)
t(15;17) is diagnostic for a specific acute promyeloid leukemia (APML), which can be treated with _________
retinoic acid
FISH probe panels are used for
initial differential diagnosis, and as a means to monitor treatments or disease progression
fluorescence-labeled probes
centromere
locus specific
fusion/dual fusion
SNP chromosomal microarrays consist of
synthetic DNA oligomers ‘spotted’ onto a ‘platform’ (usually a specially treated, microscope slide called a bead chip) using robotic technologies
CMA Methods
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
The SNP platform provides information on _________ and on _________, possibly revealing autosomal recessive conditions
intensity
runs of homozytosity
The SNP platform provides information on intensity and on runs of homozygosity, possibly revealing _________
autosomal recessive conditions
CMA testing frequently reveals _________ that cannot be seen by standard cytogenetics and light microscopy.
duplications or deletions of genetic material
Copy number variants [CNVs]
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.
all human populations contain multiple genomic variants—that is
duplications or deletions within the DNA for which there is no phenotypic consequence. These cannot be detected at the chromosome level
Test protocol (algorithm) used for
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)
Test protocol used if- (4)
- If deletion or duplication is detected by CMA consult DGV
- Parental FISH studies will be offered to determine if this finding is a rare, normal, familial variant.
- 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. - 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.
centromere probe used for
Enumeration – leukemias
Locus specific probe used for
Deletion–leukemias
Fusion or Dual Fusion probe used for
Translocations-
leukemias
