Cytogenetics

Question 1

Karyotype

Answer 1

● Shows an entire set of chromosomes with delineated bands
● Useful for visualizing large deletions, duplications, translocations, and inversions
● Resolution is too poor to detect microdeletions and duplications

Question 2

Fluorescence in situ hybridization (FISH)

Answer 2

● Utilizes sequence complementary to the region of interest
● Fluorescent hybridization signals euploidy or aneuploidy of the region
● Can detect deletions >0.5-1Mb long and duplications >1 Mb long
● Resolution is too poor for smaller deletions/duplications
● Limited in that you must know what region to look for
● Useful for parental studies when CMA detects a large enough deletion or duplication in a
child
● Useful for whole chromosome aneuploidy analysis (fast turnaround for trisomy 21,
usually still confirmed with karyotype or CMA)

Question 3

Chromosomal microarray analysis (CMA)/ Array comparative genomic hybridization (aCGH)

Answer 3

Oligo-array– detects microdeletions and duplications, cannot detect balanced
rearrangements such as inversions and translocations
● SNP-array – detects loss of heterozygosity/regions of heterozygosity, uniparental disomy,
and triploidy
o Detected by quantitative change rather than CGH
● MOST clinicians will utilize a combo oligo/SNP chip to have complete coverage
● Limited by interpretation of CNVs – not all are pathogenic, some VUS

Question 4

Indications for microarray analysis

Answer 4

● Multiple congenital anomalies not specific to a well-delineated syndrome
● Idiopathic/non-syndromic developmental delay/intellectual disability
● Autism spectrum disorder
● Prenatal patients with one or more major structural anomalies on ultrasound
● May be useful for products of conception