Definition
Mutation = a permanent, heritable change in the nucleotide sequence of DNA.
Classification BY Extent
| Type | Meaning |
|---|
| Point (gene) mutation | A single base changed, added or lost |
| Chromosomal | Deletion, duplication, inversion, translocation |
| Genomic | Change in chromosome number — aneuploidy, polyploidy |
Point Mutations
| Type | Change | Consequence | Example |
|---|
| Silent | Base changed but the same amino acid is coded | No effect — because the code is degenerate | — |
| Missense | A different amino acid | Altered protein, may be mild or severe | Sickle cell disease (Glu → Val) |
| Nonsense | Codon becomes a stop | Truncated, usually non-functional protein | β-Thalassaemia |
| Frameshift | Insertion or deletion not a multiple of three | Every codon downstream altered — usually the most damaging | Duchenne muscular dystrophy |
| In-frame deletion | Loss of a multiple of three bases | One or more amino acids missing; frame preserved | Cystic fibrosis ΔF508 |
| Triplet repeat expansion | A trinucleotide repeated excessively | Anticipation — earlier and more severe in each generation | Huntington disease, fragile X |
Transition and transversion
- Transition — purine to purine, or pyrimidine to pyrimidine; the commoner
- Transversion — purine to pyrimidine or the reverse
Mutagens
| Type | Examples | Effect |
|---|
| Physical | Ultraviolet light | Thymine dimers |
| — | X-rays, gamma rays | Strand breaks, free radicals |
| Chemical — base analogues | 5-Bromouracil, 2-aminopurine | Mispairing |
| Chemical — deaminating | Nitrous acid | Cytosine → uracil |
| Chemical — alkylating | Nitrogen mustard, ethyl methanesulphonate | Adds alkyl groups |
| Chemical — intercalating | Acridine dyes, ethidium bromide | Frameshift |
| Biological | Viruses, transposons | Insertional mutagenesis |
DNA Repair
| Mechanism | Repairs | Defect causes |
|---|
| Mismatch repair | Replication errors | Lynch syndrome (HNPCC) |
| Nucleotide excision repair | Thymine dimers, bulky adducts | Xeroderma pigmentosum |
| Base excision repair | Single altered bases (glycosylase) | — |
| Double-strand break repair | Breaks, by homologous recombination | BRCA1/2 mutations → breast and ovarian cancer; ataxia telangiectasia |
| Direct repair | Photolyase (not in man) | — |
Applied Aspects
- Mutation is the raw material of both evolution and disease — most are silent or harmful, a few advantageous