Cytogenetics

Cytogenetics: Basics & Karyotyping - Chromosome Charisma

• Cytogenetics: Study of chromosomes-their structure, number, inheritance, and abnormalities. Essential for diagnosing genetic syndromes.
• Chromosome Anatomy:
  • Metaphase chromosome: Two sister chromatids joined at centromere.
  • Arms: p (short, "petite" 📌) and q (long) arms. Telomeres cap chromosome ends.
  • Banding: G-banding (Giemsa stain) is most common, producing a unique pattern of light and dark bands for each chromosome.
• Karyotyping: Systematic arrangement of metaphase chromosomes by size and morphology.
  • Sample: Dividing cells (lymphocytes, amniocytes, chorionic villi, bone marrow).
  • Process: Cell culture → Mitotic arrest (colchicine) → Hypotonic treatment → Fixation → Staining → Analysis.
  • Nomenclature: e.g., 46,XX (normal female); 47,XY,+21 (male, Down syndrome).

⭐ Karyotyping can detect aneuploidies (e.g., trisomies, monosomies) and large structural rearrangements (e.g., translocations, deletions > 5-10 Mb).

Cytogenetics: Chromosomal Aberrations - Number & Structure Shuffles

Changes in chromosome number (numerical) or structure.

• Numerical: Altered chromosome count.

  • Aneuploidy: Abnormal number (not multiple of haploid set).
    • Trisomy ($2n+1$): e.g., Down (Trisomy 21), Edwards (T18), Patau (T13), Klinefelter (XXY).
    • Monosomy ($2n-1$): e.g., Turner (XO).
    • Cause: Non-disjunction.
  • Polyploidy: Extra full sets ($3n$, $4n$); often lethal.

• Structural: Chromosome breakage & rearrangement.

  • Deletion: Segment loss.
  • Duplication: Segment repetition.
  • Translocation: Segment exchange.
    • Reciprocal: Between non-homologues.
    • Robertsonian: Acrocentric fusion (📌 Robertsonian Affects Acrocentric Chromosomes - 13, 14, 15, 21, 22).
  • Inversion: Segment reversed (paracentric/pericentric).
  • Isochromosome: Mirrored arms (e.g., $i(Xq)$ in Turner).
  • Ring Chromosome: Ends fuse.

⭐ Robertsonian translocations (e.g., t(14;21)) involving acrocentric chromosomes (13, 14, 15, 21, 22) are a key cause of familial Down syndrome.

Cytogenetics: Syndromes & Techniques - Disorder Detectives' Toolkit

• Common Numerical Abnormalities (Aneuploidies):
  • Down Syndrome: Trisomy 21. 📌 Mnemonic: Drinking age is 21.
  • Edwards Syndrome: Trisomy 18. 📌 Mnemonic: Election age is 18.
  • Patau Syndrome: Trisomy 13. 📌 Mnemonic: Puberty around 13.
• Sex Chromosome Aneuploidies:
  • Klinefelter Syndrome: 47,XXY.
  • Turner Syndrome: 45,X (Monosomy X).
• Common Structural Abnormalities:
  • Cri-du-chat Syndrome: Deletion of short arm of chromosome 5 ($del(5p)$).
  • DiGeorge Syndrome: Microdeletion on chromosome 22q11.2.
• Key Diagnostic Techniques:
  • Karyotyping: Baseline analysis of chromosome number and large structural changes.
  • FISH (Fluorescence In Situ Hybridization): Detects specific DNA sequences, microdeletions/duplications (e.g., DiGeorge, Prader-Willi/Angelman).
  • Chromosomal Microarray (CMA) / Array CGH: High-resolution detection of copy number variations (CNVs); often first-tier test for unexplained developmental delay, intellectual disability, autism spectrum disorders, or multiple congenital anomalies.

⭐ FISH is crucial for rapidly detecting specific aneuploidies (e.g., trisomies 13, 18, 21, X, Y) and known microdeletion syndromes like DiGeorge (22q11.2 deletion).

High‑Yield Points - ⚡ Biggest Takeaways

• Karyotyping detects numerical and gross structural chromosomal changes.
• FISH identifies specific DNA sequences, microdeletions, and translocations like t(9;22) in CML.
• Aneuploidies (e.g., Trisomy 21, Turner's 45,X, Klinefelter's 47,XXY) are common.
• Microdeletions cause syndromes like Cri-du-chat (5p-) and DiGeorge (22q11.2).
• Chromosomal translocations are hallmarks of many leukemias and lymphomas.
• Microarray CGH detects copy number variations (CNVs) with high resolution globally across the genome an advantage over FISH and Karyotyping for unknown abnormalities .