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Structure Gone Wrong: Translocations, Deletions, Duplications

Sometimes the count is right but the chromosomes themselves are rearranged: pieces swapped, lost, or doubled. These structural changes underlie translocations, microdeletion syndromes, and the famous Philadelphia chromosome.

Translocations: pieces in the wrong place

A translocation happens when a segment of one chromosome breaks off and reattaches to a different chromosome. If no genetic material is gained or lost in the swap, it is called balanced — and a person carrying a balanced translocation is often completely healthy, because all their genes are present, just rearranged. The catch comes at the next generation: during meiosis, a balanced carrier can produce unbalanced gametes that have too much of one segment and too little of another, raising the risk of a child with extra or missing material.

A Robertsonian translocation is a special version where two whole chromosomes fuse at their centromeres into a single chromosome. When this involves chromosome 21, a carrier can pass on an effective extra copy of 21 — producing translocation Down syndrome. This is the inherited route to Down syndrome hinted at earlier, and it explains why some families have a recurrence risk that the standard, age-related trisomy does not carry.

Translocations are not only inherited. An acquired translocation in a single cell line can drive cancer. The famous Philadelphia chromosome is a swap between chromosomes 9 and 22 that fuses two genes into one overactive growth signal, a defining feature of chronic myeloid leukemia. The same cytogenetic logic — broken ends rejoining in the wrong combination — runs from inherited conditions to acquired tumors.

Deletions, duplications, and microdeletions

A chromosomal deletion is a missing segment, so the genes within it are present in only one copy instead of two. A chromosomal duplication is the reverse: a doubled segment, giving three copies of those genes. Both are forms of copy number variation, and both shift gene dose for everything in the affected stretch — which is why even a small change can have outsized effects if the right genes are involved.

When a deletion is too small to see on a routine karyotype but still removes several neighbouring genes, the result is a microdeletion syndrome. Because the lost stretch spans multiple genes, these conditions present as a recognizable cluster of features rather than a single trait — and detecting them needs higher-resolution tools than the microscope alone, which is the subject of the next guide.

Structural changes at a glance:

  Deletion      ...[A B C D E]...  -->  ...[A B   D E]...   (lost C)
  Duplication   ...[A B C D E]...  -->  ...[A B C C D E].   (extra C)
  Translocation chr-A: [..X..]  chr-B: [..Y..]
                -->   chr-A: [..Y..]  chr-B: [..X..]

  Balanced translocation: all material present, just relocated
      -> carrier usually healthy, but gametes may be unbalanced
  Microdeletion: deletion too small for the karyotype to resolve
      -> needs FISH or microarray to detect
Deletions remove a segment, duplications double it, and translocations move it elsewhere. Microdeletions are too small for the karyotype to catch.