Mutations and Their Types Quiz

Mutations

• Permanent changes in DNA sequence
• Can be reflected in mRNA base sequence and protein amino acid sequence
• Can cause genetic diseases

Types of Mutations

• Point Mutation (Single-base substitution)
  • Substitution of original base in gene with another
  • Transition: Purine replaced by purine or pyrimidine replaced by pyrimidine (e.g., A >>> G or C >>> T)
  • Transversion: Purine replaced by pyrimidine or vice versa (e.g., T >>> A, C >>> A, T >>> G, C >>> G)
  • Can affect coding or regulatory regions of a gene
  • Can alter gene expression if regulatory sequences are affected
  • Can produce disease alleles within coding regions

Consequences of Point Mutation

• Silent Mutation
  • Changed base may code for the same amino acid
  • No effect on protein structure
  • Usually occurs in the 3rd codon position (Wobble’s theory)
• Missense Mutation
  • Changed base may code for a different amino acid
  • Can have variable effects on protein structure
  • Acceptable Missense: May result in normal functional protein (e.g., hemoglobin β-chain)
  • Partially Acceptable Missense: May produce a protein with altered function (e.g., Hb S)
  • Unacceptable Missense: May produce a non-functional protein (e.g., Hb M)
• Nonsense Mutation
  • Changed base creates a termination codon
  • Results in premature termination of translation
  • Produces a shortened (truncated) protein

Hereditary Hemochromatosis (HH)

• Common genetic disease
• Caused by missense mutations in the HFE gene (Human homeostatic iron regulator protein)
• Mutations used to screen at-risk populations
• Results in iron overload, leading to liver damage, diabetes, skin pigmentation, and heart failure

Frame Shift Mutation

• Deletion or insertion of one or more nucleotides in DNA
• Alters mRNA reading frame
• Produces different amino acids
• Can have significant impact on protein structure

Trinucleotide Repeat Expansion

• Amplification of a three-base sequence repeated in tandem
• Causes extra copies of one amino acid in the protein
• Example: Huntington disease (expansion of CAG codon in Huntington protein gene)
• Results in an abnormally long protein, leading to toxic fragments and neuronal aggregation
• Fragile X syndrome (expansion of CGG codon)

Splice Site Mutations

• Mutations at splice sites alter intron removal from pre-mRNA
• Produce abnormal proteins
• Can lead to gene silencing and lack of protein production

Polymorphisms

• Genotype changes that may or may not result in phenotypic changes
• Phenotypic changes can be harmless, increase susceptibility to disease, or cause disease
• Defined as sequence variation at a locus in >1% of a population
• Primarily occur in non-coding regions (introns and intergenic regions)

Types of Polymorphisms

• Single-base changes:
  • Single nucleotide polymorphisms (SNPs)
  • Account for 90% of human genome variation
• Tandem Repeats:
  • Variable number of tandem repeats (VNTRs)
  • Short sequences of DNA repeated in tandem
  • Number of repeats varies between individuals
  • Serve as a molecular "fingerprint"

Clinical Implications of Polymorphisms

• Paternity testing: VNTRs used in fingerprinting
• Disease susceptibility: Can increase susceptibility to diseases like cancer and cardiovascular diseases
• Disease screening: Used to screen high-risk individuals

Summary

Mutations are permanent changes in DNA sequence that can lead to altered proteins and genetic diseases. Different types of mutations, including point mutations, frame shift mutations, trinucleotide repeat expansions, and splice site mutations, can have a range of effects on protein structure and function. Polymorphisms, common variations in DNA sequence, can be harmless, increase disease susceptibility, or cause disease.

Test your knowledge on mutations, including point mutations and their consequences. This quiz covers various types of mutations, how they affect DNA and protein sequences, and their potential to cause genetic diseases. Make sure to review the concepts of silent and missense mutations.