I. Introduction
Chromosomal mutations (also called chromosomal aberrations) are large-scale changes in chromosome number or structure. Unlike single-gene mutations, they affect large regions of the genome, sometimes involving hundreds of genes.
- They arise due to errors in meiosis, mitosis, or DNA repair.
- Consequences: miscarriage, congenital malformations, infertility, developmental delay, or cancer.
- Types:
- Numerical aberrations (changes in whole chromosome number).
- Structural aberrations (rearrangements within or between chromosomes).
II. Numerical Chromosomal Aberrations
1. Aneuploidy
- Definition: gain or loss of individual chromosomes (≠ exact multiple of haploid set).
- Mechanism: nondisjunction during meiosis I or II → gametes with abnormal chromosome number.
- Types:
- Monosomy (2n–1): loss of one chromosome. Example: Turner syndrome (45,X).
- Trisomy (2n+1): extra chromosome. Examples:
- Trisomy 21 → Down syndrome (47,XX,+21 or 47,XY,+21).
- Trisomy 18 → Edwards syndrome.
- Trisomy 13 → Patau syndrome.
- Clinical note: Most autosomal monosomies are lethal in embryogenesis.
2. Polyploidy
- Definition: presence of extra full haploid sets (3n, 4n).
- Mechanism: failure of meiotic cytokinesis or dispermy (two sperm fertilizing one egg).
- Examples:
- Triploidy (3n = 69 chromosomes).
- Tetraploidy (4n = 92 chromosomes).
- Clinical outcome: usually lethal, major cause of early miscarriage.