Chromosomal Mutations: Types and Examples

Chromosomal Mutations

Chromosomal mutations translate into two types of abnormalities, visible by light microscopy: numerical and structural.

Numerical Alterations of Chromosomes

There are two main types:

• Euploidies: Numerical alterations affecting the entire genome. Individuals may have two, three, or four sets of similar chromosomes (monoploidy, triploidy, and tetraploidy, respectively).
• Aneuploidy: Affects only one pair of chromosomes, while the rest remain the same. Individuals are described as monosomic, trisomic, or tetrasomic, depending on the number of copies of the affected chromosome.

Structural Alterations of Chromosomes

• Deletions: Loss of a chromosome fragment, which can be interstitial (within the chromosome arm) or terminal (at the end of the chromosome arm). Example: Deletion in region 11 of chromosome 22 results in DiGeorge Syndrome (characterized by multiple malformations, agenesis of the thymus and parathyroid, and cardiac defects). Deletion in region 13 of chromosome 11 results in WAGR Syndrome.
• Duplications: A fragment of a chromosome, either terminal or interstitial, is duplicated. Sometimes, this affects whole genes, although this is generally less harmful. There are different types of duplications:
  • Tandem Duplication: The duplicated fragment is repeated in the same order, changing the chromosome's morphology.
  • Tandem Duplication in Reverse: The duplicated fragment is the same but in reverse order compared to the original.
  • Displaced Segment Duplication: The duplicated fragment is not necessarily located below the original but can be elsewhere on the chromosome.

Example: Charcot-Marie-Tooth Disease, where chromosome 17 has three copies of a gene. The normal gene encodes for peripheral myelin; having three copies increases the gene product, causing demyelination.

Translocations: A chromosomal rearrangement where chromosomes exchange segments between non-homologous chromosomes, or a fragment moves to a different chromosome. Inversions: A fragment of a chromosome rotates 180 degrees and is placed in the reverse position, but it is welded in the same original location. Isochromosomes: Result from abnormal division of the centromere. Normally, homologous chromosomes separate by a longitudinal split. In isochromosomes, the split is transverse. This results in duplicated genes on one arm and missing genes on the other. Gametes formed from these chromosomes will be both duplicated and incomplete.