Cytogenomics is the study of chromosome structure and function using genetic and molecular techniques. It combines traditional cytogenetics with advanced genomics to analyze chromosome abnormalities.
Here I present: Three (3) cytogenomic methods used on blood samples: karyotype, FISH, and optical genome mapping (OGM).
Karyotype vs FISH vs OGM (optical genome mapping )
A. Cytogenomics Comparison.
1. Karyotype (G-banded metaphase cytogenetics).
Visualizes whole chromosomes during metaphase.
Requires actively dividing blood or marrow cells.
Shows large structural changes.
2. FISH (Fluorescence In Situ Hybridization)
Uses fluorescent DNA probes to bind specific genomic regions.
Works on metaphase or interphase cells (dividing not required).
Detects targeted abnormalities.
3. OGM (optical genome mapping)
High-molecular-weight (HMW) DNA is stretched in nanochannels.
Direct imaging of labeled sequence motifs across entire genome.
Detects structural variants (SV) genome-wide with very high resolution.
B. RESOLUTION.
karyotype~5–10 Mb (low).
FISH~100 kb (targeted)
OGM~500 bp to ~5 kb (high)
C. What each test is best for.
1. Karyotype.
Constitutional aneuploidies (Down syndrome 47,XX,+21; Turner; etc.)
Large deletions/duplications.
Balanced translocations visible under microscope.
Leukemia metaphase abnormalities (e.g., t(8;21), t(15;17), complex karyotype).
2. FISH.
Confirming a known, suspected, or common abnormality
Rapid aneuploidy testing (trisomy 13/18/21, XY)
Fusion detection:
BCR-ABL (CML).
PML-RARA (APL).
EWSR1 rearrangements.
Small deletions/duplications (microdeletions).
Mosaicism assessment .
Interphase analysis when culture fails.
3. OGM.
Genome-wide structural variant detection:
Translocations (even cryptic).
Inversions.
Insertions.
Repeat expansions.
Complex genomic rearrangements.
Hematologic malignancies (AML, MDS, ALL) where the entire SV landscape is needed
Replacing metaphase cytogenetics + FISH panels with one assay.
Detecting abnormalities smaller than karyotype or non-targeted by FISH.
D. What each method cannot do.
1. Karyotype cannot:
Detect microdeletions/microduplications.
Detect small rearrangements (<3–5 Mb).
Work on non-dividing cells.
Detect many cryptic fusions.
2. FISH cannot:
Do genome-wide discovery → only sees what you probe for.
Give full chromosomal architecture.
Map breakpoints precisely.
Detect completely unknown fusions.
3. OGM cannot:
Detect single-nucleotide variants (SNVs).
Replace sequencing (needs complementary NGS).
Detect very tiny CNVs below ~500 bp.
Be used in routine prenatal settings.
E. Single sentence summary.
1. Karyotype = big picture, low resolution.
2. FISH = targeted, medium resolution.
3. OGM = high resolution for structural variants, genome-wide.
