Chromosomal Abnormalities: Numerical & Structural
| Abnormality Type | Genetic Mechanism & Examples |
|---|---|
| Aneuploidy | Nondisjunction during meiosis (typically maternal age-related). Trisomy 21 (Down), Trisomy 18 (Edwards), Trisomy 13 (Patau). |
| Translocation | Robertsonian: Fusion of acrocentric chromosomes (e.g., 14;21). Reciprocal: Exchange of segments between non-homologous chromosomes (e.g., Philadelphia chromosome t(9;22) in CML). |
| Deletions | Loss of a chromosome segment. Cri-du-chat (5p deletion) and Williams syndrome (7q11.23 deletion). |
| Microdeletions | Too small to be detected by standard karyotype; requires FISH (Fluorescence In Situ Hybridization) or chromosomal microarray. DiGeorge (22q11) is the classic board-tested example. |
High-Yield Core Realities:
- Maternal Age Effect: The classic correlation between increased maternal age and the incidence of aneuploidy (specifically Trisomy 21) is due to the prolonged meiotic arrest of oocytes, which increases the likelihood of spindle attachment errors.
- Philadelphia Chromosome t(9;22): A classic board topic. This reciprocal translocation creates a fusion gene (BCR-ABL) with constitutive tyrosine kinase activity, driving chronic myeloid leukemia. It serves as a major target for tyrosine kinase inhibitor therapy (e.g., Imatinib).
- FISH vs. Karyotype: Use a standard karyotype to identify large-scale numerical changes (aneuploidy) or balanced translocations. Use FISH for targeted detection of microdeletions or specific gene amplifications.
- Educational Resource: For comprehensive high-yield notes, clinical cases, and diagnostic algorithms related to chromosomal genetics, visit mymedschool.org, which features free medical questions tailored for board preparation.