Types of Mutations Flashcards
What is a point mutation?
A point mutation is a change in a single nucleotide in the DNA sequence. It can be a substitution, insertion, or deletion of a single base
What are the three types of point mutations?
1️⃣ Missense Mutation → A single nucleotide change alters the amino acid sequence
Normal DNA: GAG → GAA (Encodes Glutamic Acid)
Mutated DNA: GTG → GUA (Encodes Valine)
2️⃣ Nonsense Mutation → A single nucleotide change creates a premature stop codon, leading to a truncated, nonfunctional protein.
Normal DNA: TAC → UAC (Tyr - Tyrosine)
Mutated DNA: TAC → UAA (STOP codon)
3️⃣ Silent Mutation → A single nucleotide change does not alter the amino acid sequence, often due to codon redundancy.
Normal DNA: CGA → CGA (Arg - Arginine)
Mutated DNA: CGG → CGA (Still Arginine!)
Are missense mutations always harmful?
No. Some missense mutations are neutral if they result in an amino acid with similar properties, while others can be deleterious if they disrupt protein structure/function (e.g., sickle cell anemia)
What is a frameshift mutation?
A frameshift mutation occurs when nucleotides are inserted or deleted in numbers not divisible by three, shifting the reading frame and altering downstream amino acids
Why are frameshift mutations often more severe than point mutations?
Because they disrupt the entire reading frame, leading to widespread changes in amino acids and often creating premature stop codons, which result in nonfunctional proteins
Give an example of a disease caused by a frameshift mutation.
Cystic Fibrosis (ΔF508 mutation in the CFTR gene) → A deletion of three bases removes a phenylalanine residue, leading to misfolded CFTR protein
What is a nonsense mutation?
A nonsense mutation introduces a premature stop codon, leading to truncated proteins that are often nonfunctional
What is a stop-loss mutation?
A stop-loss mutation removes a natural stop codon, causing the protein to be abnormally extended, potentially affecting function
What are insertion and deletion mutations?
Insertion → Addition of one or more nucleotides into a DNA sequence.
Deletion → Removal of nucleotides from the DNA sequence.
Both can cause frameshifts if not in multiples of three
How can insertions and deletions affect gene function?
If within coding regions, they may alter the reading frame, producing nonfunctional proteins.
If in regulatory regions, they can increase or decrease gene expression
What is a splice-site mutation?
A mutation that alters the recognition of exon-intron boundaries, leading to abnormal mRNA splicing
What happens if a splice-site mutation disrupts mRNA processing?
Exon skipping → Some exons may be excluded, altering the protein sequence.
Intron retention → Some introns may not be removed, leading to incorrectly translated proteins
What are the main types of chromosomal mutations?
Deletion → A large segment of a chromosome is lost.
Duplication → A section of the chromosome is copied, increasing gene dosage.
Inversion → A segment is reversed end-to-end.
Translocation → A fragment of one chromosome attaches to another
What is a copy number variation (CNV)?
CNVs involve duplication or deletion of large DNA segments, affecting gene dosage and potentially contributing to diseases
Based on Molecular Change (How the DNA is Altered)
✅ Point Mutations (Single Nucleotide Variants, SNVs)
1) Substitution → One base is replaced by another.
- Transition → Purine ↔ Purine (A ↔ G) or Pyrimidine ↔ Pyrimidine (C ↔ T).
- Transversion → Purine ↔ Pyrimidine (A/G ↔ C/T).
2) Silent Mutation → No change in the amino acid (synonymous mutation).
3) Missense Mutation → Changes an amino acid (non-synonymous mutation).
4) Nonsense Mutation → Introduces a premature stop codon.
✅ Insertions & Deletions (Indels)
Frameshift Mutation → Indel that is not a multiple of 3, shifting the reading frame.
In-frame Mutation → Indel of 3 (or multiples of 3) nucleotides, keeping the reading frame intact.
✅ Splice Site Mutations
Disrupts normal splicing (e.g., exon skipping, intron retention, activation of cryptic splice sites).
Based on Effect on Protein Function
✅ Loss-of-Function Mutation
Causes a nonfunctional or absent protein (e.g., nonsense mutations, frameshifts, large deletions).
Example: BRCA1 tumor suppressor mutations in cancer.
✅ Gain-of-Function Mutation
Creates a hyperactive or new function for a protein.
Example: FGFR3 mutation in achondroplasia (causes excessive inhibition of bone growth).
✅ Dominant-Negative Mutation
The mutated protein interferes with the function of the normal protein.
Example: Mutant p53 in cancer, which inhibits tumor suppression.
Based on Location in the Genome
✅ Coding Region Mutations
Affects protein-coding exons (e.g., missense, nonsense, frameshift mutations).
✅ Non-Coding Region Mutations
Promoter Mutations → Affect gene transcription levels.
Enhancer/Silencer Mutations → Affect gene regulation.
Splice Site Mutations → Disrupt RNA splicing.
UTR (Untranslated Region) Mutations → Can affect RNA stability and translation.
Based on Inheritance (Germline vs. Somatic)
✅ Germline Mutations
Inherited mutations in sperm or egg cells that affect all cells in the offspring.
Example: BRCA1 mutations increasing breast cancer risk.
✅ Somatic Mutations
Acquired mutations that occur in non-germline (body) cells.
Example: TP53 mutations in tumors.
Based on Phenotypic Effect
✅ Neutral Mutation
No significant effect on function or fitness.
✅ Beneficial Mutation
Provides an advantage (e.g., CCR5-Δ32 mutation conferring HIV resistance).
✅ Harmful Mutation (Pathogenic Mutation)
Causes disease (e.g., CFTR mutation in cystic fibrosis).
Based on Scale of Genetic Change
✅ Small-Scale Mutations
Point mutations (substitutions, insertions, deletions).
✅ Large-Scale Mutations (Chromosomal Mutations)
Duplications → Extra copies of a segment.
Deletions → Loss of a DNA segment.
Inversions → A DNA segment is flipped.
Translocations → A segment moves to a different chromosome.
