A resposta resumida
A mutation is simply a change in the DNA letters. The word sounds alarming, but most mutations do nothing at all — they land in regions that do not matter, or they change a letter without changing the protein. You carry dozens of new mutations your parents did not have. Only a small minority cause disease, and some are protective.
Mutations range from single-nucleotide substitutions through small insertions and deletions to large structural rearrangements. Consequence depends on location and type: substitutions may be silent, missense or nonsense; insertions and deletions not in multiples of three shift the reading frame. Clinical classification runs from benign through variant of uncertain significance to pathogenic. Germline variants are inherited; somatic variants are acquired and are not.
The kinds that matter for editing
| Type | What happens | Which editing approach fits |
|---|---|---|
| Point substitution | One letter changed | Base editing, if the change is one it can make; otherwise prime editing |
| Small insertion or deletion | A few letters added or lost, often shifting the reading frame | Prime editing |
| Nonsense | A premature stop signal ends the protein early | Base or prime editing, depending on the letter |
| Large deletion | A whole exon or gene region lost | Gene addition, or integrase-based insertion |
| Repeat expansion | A short sequence repeated too many times | Excision or silencing |
| Toxic gain of function | The protein acquires a new, harmful behaviour | Knockout or silencing — adding a good copy will not help |
Which category a disease falls into determines almost everything about how it could be treated.
Germline versus somatic
A germline change is present in every cell and is passed to children. A somatic change happens in some cells during life and is not inherited. All approved and clinical gene-editing therapy is somatic. Editing the germline — embryos, eggs or sperm — is a different act legally and ethically, and is prohibited or unapproved for clinical use in most countries.
Sources
- National Human Genome Research Institute
Talking Glossary of Genomic Terms ↗ - MedlinePlus Genetics, U.S. National Library of Medicine
Help Me Understand Genetics ↗