Arrange Chromosomes
A karyogram is not a random collage of chromosomes; it is a highly structured diagram that follows rigorous international standards defined by the International System for Human Cytogenomic Nomenclature (ISCN). This standardization allows a cytogeneticist in New York to instantly interpret a karyogram produced in Tokyo. The arrangement is hierarchical, based on Size, Centromere Position, and Banding Pattern
The Basic Layout (Groups A–G)
Human chromosomes (22 autosomes + X/Y) are arranged in 7 Groups (A through G) generally based on decreasing size
- Group A (1–3): Large metacentric (1, 3) and submetacentric (2)
- Group B (4–5): Large submetacentric
- Group C (6–12 + X): Medium submetacentric. This is the most difficult group to sort without high-quality banding
- Group D (13–15): Medium acrocentric (with satellites)
- Group E (16–18): Small metacentric (16) and submetacentric (17, 18)
- Group F (19–20): Small metacentric
- Group G (21–22 + Y): Small acrocentric (with satellites)
Orientation Rules
Within the karyogram, every chromosome must be oriented vertically
- Up/Down: The Short Arm (p-arm) is always placed at the top. The Long Arm (q-arm) is always at the bottom
- Centromere Alignment: The centromeres of all chromosomes in a row should be aligned horizontally. This visual “belt line” allows the eye to quickly compare the lengths of the p-arms and q-arms across the genome
- Exceptions (Acrocentrics): For acrocentric chromosomes (D and G groups), the p-arm is the satellite stalk. These are still oriented with the satellite up
Pairing Rules (Homologs)
- Homologous Pairs: The two copies of Chromosome 1 are placed side-by-side
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Identification: The laboratory scientist uses specific banding landmarks to distinguish similar chromosomes (e.g., distinguishing Chromosome 4 from 5)
- Chromosome 4: Has a distinct light band at 4q26 and is generally less dense
- Chromosome 5: Has a distinct dark band at 5q12
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Sex Chromosomes: Placed at the very end of the karyogram, after Chromosome 22
- Standard format: X first, then Y
Arranging Abnormalities (ISCN Rules)
When structural abnormalities are present, the arrangement changes to highlight the defect
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Translocations
- If there is a translocation (e.g., between 9 and 22), the derivative chromosomes (the products of the mix) are placed next to their normal homologs
- Position 9: Normal Chromosome 9 goes on the left; Derivative 9: goes on the right
- Position 22: Normal Chromosome 22 goes on the left; Derivative 22: goes on the right
- Why: This allows for a direct side-by-side comparison of the normal vs. abnormal structure
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Deletions/Inversions
- Similarly, the abnormal chromosome is placed to the right of the normal homolog
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Unknown Markers
- If there is a “Marker Chromosome” (unidentifiable), it is placed at the very end, after the Sex Chromosomes, labeled “mar”
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Trisomy
- The three copies are placed together in the group (e.g., three chromosomes in the position for Chromosome 21)
Software Assistance vs. Human Expertise
Modern automated karyotyping systems (e.g., Ikaros, GenASIs) use AI to classify chromosomes based on size and banding classifiers
- The “Classifier”: The software proposes a karyogram layout
- The Trap: Automated classifiers frequently make mistakes, especially with C-group chromosomes (swapping 10 and 12) or failing to recognize abnormal chromosomes (placing a derivative 9 in the Group C pile)
- The Mandate: The laboratory scientist must manually verify and correct every single chromosome assignment. Accepting the software’s suggestion without scrutiny is a primary cause of diagnostic error