Mutations and Gene Editing
How DNA sequence changes arise and affect gene products, and how CRISPR-based editing can target specific genomic sequences.
Mutation
A change in genetic material. In cellular organisms this normally means a change in the DNA nucleotide sequence; the change can be copied when an affected cell divides.
Small-scale sequence changes
- Substitution: one nucleotide is replaced by another. A single-nucleotide substitution may be silent, missense, or nonsense depending on the codon change.
- Insertion: one or more nucleotides are added.
- Deletion: one or more nucleotides are removed.
A frameshift occurs when nucleotides are inserted or deleted from a coding sequence in a number that is not a multiple of three. It changes the grouping of downstream codons and can substantially alter the resulting protein.
Single-nucleotide variants
A single-nucleotide polymorphism (SNP) is a common single-base variant in a population. Some SNPs have no measurable phenotypic effect, while others alter gene regulation, RNA processing, or protein sequence.
Where mutations come from
Mutations can arise spontaneously through DNA replication or repair errors. Mutagens such as ultraviolet radiation, ionizing radiation, and some chemicals can increase mutation rate. Mutations do not appear because an organism needs a particular change.
Consequences depend on context
| Location/effect | Possible consequence |
|---|---|
| Non-coding region | No detectable effect, or altered regulation if a control element is affected |
| Synonymous coding change | Same amino acid; may still influence expression or RNA processing in some cases |
| Missense coding change | Different amino acid; effect depends on position and chemical change |
| Nonsense change | Premature stop codon and shortened protein |
| Frameshift | Many downstream codons altered; often severe for the encoded protein |
Germline and somatic mutations
A mutation in a germline cell can be transmitted to offspring if it is present in a gamete that contributes to a zygote. Somatic mutations occur in body cells and are generally not inherited by offspring, although they can contribute to diseases such as cancer within the individual.
Cancer and mutation
Cancer can arise when mutations alter genes that regulate cell proliferation, DNA repair, or cell death. Activating mutations in proto-oncogenes or loss-of-function changes in tumor-suppressor genes can contribute to uncontrolled growth, usually alongside additional changes.
CRISPR-Cas9
- A guide RNA contains a sequence designed to base-pair with the target DNA.
- The guide RNA directs Cas9 to a complementary target adjacent to an appropriate PAM sequence.
- Cas9 cuts the DNA.
- Cellular DNA-repair pathways then repair the break. Repair can disrupt a gene or, when a suitable repair template is used, introduce a designed sequence change.
Editing can produce unintended sequence changes, mosaicism, or incomplete targeting. Medical and heritable uses also raise safety, consent, equity, and governance questions that must be considered separately from technical feasibility.
Conserved sequences
A sequence that changes little across species or over evolutionary time is described as conserved. Strong conservation can suggest functional importance because harmful changes at that site may be removed by natural selection.