Ch15MutationsV3+Rev_31747316ad4aec4e5dc5f7ec1703df6f

Mutations Overview

• A mutation is a change in the DNA sequence.

What is a Mutation?

• Definition: A mutation refers to any alteration in the DNA sequence.

DNA Structure

• Components of DNA: DNA consists of strands with sequences representing genes (Gene 1, Gene 2, Gene 3).

• Transcription & Translation: This process involves converting DNA into mRNA and then into proteins, where codons in mRNA determine the sequence of amino acids in proteins.

Types of Mutations

Point Mutation

• Definition: A point mutation involves a change where one nucleotide is replaced with another.

  • Subtypes:

    • Silent Mutation: No change in amino acid sequence despite a change in DNA.

    • Missense Mutation: Leads to a different amino acid being coded for.

    • Nonsense Mutation: Creates a premature stop codon, truncating the protein.

Frameshift Mutation

• Definition: A frameshift mutation occurs due to the insertion or deletion of nucleotides, altering the reading frame of the DNA.

  • Subtypes:

    • Insertion: Introducing extra nucleotides into the sequence.

    • Deletion: Removing nucleotides from the sequence.

Detailed Analysis of Mutations

Silent Mutation

• Example: Changes in nucleotide sequences that do not affect amino acid outcomes, e.g., DNA Codon change from CCG to CCA still codes for Glycine.

• Characteristics: Changes in DNA may lead to the same protein being produced, maintaining function.

Missense Mutation

• Example: The substitution of one nucleotide, changing an amino acid, e.g., DNA Codon change from CCG to TCG changes Glycine to Serine.

• Clinical Relevance: Sickle Cell Anemia is a classic example, caused by a single point mutation leading to a faulty hemoglobin gene.

Nonsense Mutation

• Impact: Results in a shortened protein that lacks crucial amino acids, making it nonfunctional, e.g., UAG codes for a stop codon.

• Example: DNA change leading from UA codon to UAG prematurely halts translation.

Frameshift Mutations

• Impact: Changes protein synthesis drastically since it alters the translation reading framework.

  • Example 1: Addition or deletion leading to early stop or extensive missense,

  • Example 2: Insertion or deletion that occurs in multiples of three preserves the reading frame but alters the protein by adding or omitting amino acids.

Effects of Mutations

• Germ-line Mutations: Affect reproductive cells, leading to mutations being passed to offspring, affecting the entire organism.

• Somatic Mutations: Occur in non-reproductive cells, typically not inherited by offspring, but can affect patches of cells in the organism.

Causes of Mutations

Spontaneous Mutations

• Mechanisms: Errors during DNA replication, metabolic byproducts, and natural changes in nucleotide structure can cause spontaneous mutations.

• Transposons: Jumping genes that can insert themselves into other genes, leading to mutations.

Induced Mutations

• Caused by: External environmental agents including chemicals and physical agents like UV light, which can create thymine dimers.

DNA Repair Systems

• Mismatch Repair: Corrects mismatched bases after DNA replication.

• Nucleotide Excision Repair: Recognizes and repairs abnormal bases and damages like thymine dimers.

Clinical Example of DNA Repair Deficiency

Xeroderma Pigmentosa

• Description: A genetic disease caused by defective DNA repair mechanisms.

• Symptoms: Increased sensitivity to sunlight, leading to blisters, freckles, precancerous lesions, and cancer.

Unique Mutations in Species

• Bully Mutation: Changes in the Myostatin gene lead to increased muscle growth in certain dog breeds and cattle.