Chapter 11: Genome alterations - mutation part 1

Mutations can be classified based on the type of cell they first occur in terms: germline mutation, somatic mutation

*Germline mutation*: mutation that occurs in gametes or in cells that eventually become gametes. • Mutation might be transmitted to offspring • Essentially all cells in offspring will carry the mutation *Somatic mutation*: mutation that occurs in non-reproductive, i.e. somatic cells. • Mutation can not transmitted to offspring • Mutation can be transmitted to daughter cells through mitosis

Mutation

*Mutation: A heritable change in the DNA sequence.* • Mutations can have negative effects on an organism • Mutations can have no effect on an organism • Mutations can have positive effects on an organism Heritable can mean that a mutation is transmitted to offspring through meiosis (gametes), or it can mean that a mutation is transmitted to daughter cells through mitosis.

Learning objectives

Define mutation and describe how mutations can affect an individual, including the types of macromolecules that can be affected and the ways in which a mutation can affect the overall health and well-being of an individual. Classify mutations based on the type of cell they first occur in and describe the effect each class of mutation can have on future generations of offspring. Classify mutations based on the type of alteration that occurs in the DNA and, if the mutation happens within the coding region of a gene, further classify the mutation according to how the resulting protein is affected. Predict how a particular mutation would affect an amino acid sequence after transcription and translation of a template strand of DNA.

silent mutation

If a nucleotide substitution in DNA does not result in a change in an amino acid in a protein, it can also be described as a *silent mutation.*

nonsense mutation

If a nucleotide substitution in DNA results in replacement of a codon for an amino acid with a stop codon, it can also be described as a *nonsense mutation.*

Sense mutation

If a nucleotide substitution in DNA results in replacement of a stop codon with one that codes for an amino acid, it can also be described as a *sense mutation*.

Sense mutation II

If a nucleotide substitution in DNA results in replacement of a stop codon with one that codes for an amino acid, it can also be described as a sense mutation.

Frameshift mutation

If an insertion/deletion in DNA results in a shift in the codon reading frame, it can also be described as a *frameshift mutation*. Often a frameshift will result in an absent or nonfunctional variant protein.

General properties of mutations

Mutations can be classified in a variety of ways: • What type of cell the mutation first occurs in • Type of alteration that occurs in the DNA • Source of the mutation

Mutations can be classified based on the type of alteration that occurs in the DNA terms: point mutation, nucleotide mutation, insertion, deletion, trinucleotide repeat expansion, chromosomal alteration

*Point mutation*: A mutation that involves alteration of a single nucleotide in DNA. 1. *Nucleotide substitution*- a point mutation that results from replacement of one nucleotide in DNA with another nucleotide. a) Missense mutation- a nucleotide substitution that causes replacement of one amino acid with another amino acid in a protein. b) Silent mutation- a nucleotide substitution that does not cause a change in an amino acid in a protein. c) Nonsense mutation- a nucleotide substitution that causes replacement of a codon for an amino acid with a stop codon. d) Sense mutation- a nucleotide substitution that causes replacement of a stop codon with one that codes for an amino acid. 2. *Insertion or deletion*- a point mutation that results from addition or removal of one nucleotide in DNA. a) Frameshift mutation- an insertion or deletion that causes a shift in the codon reading frame. *Trinucleotide repeat expansion*: Mutation that results in expansion of the number of trinucleotide repeats. *Chromosomal alteration*: Mutation that involves >1000 bp (Chapter 6) Notes: Can have several point mutations in a row! Although you can categorize a mutation based on what happens to the resulting amino acid sequence, mutations occur in the DNA!

Point mutations: insertion or deletion mutation & frameshift mutation

*Point mutation: a mutation that involves alteration of a single nucleotide in DNA.* -If a point mutation results in addition or removal of one nucleotide in DNA, it can also be described as an *insertion or deletion mutation*. -If an insertion/deletion in DNA results in a shift in the codon reading frame, it can also be described as a *frameshift mutation*. Can have several insertions or deletions in a row. Anything other than a multiple of three will cause a frameshift!

Types of DNA alternations terms: point mutation, nucleotide substitution mutation, missense mutation

*Point mutation: a mutation that involves alteration of a single nucleotide in DNA.* If a point mutation results in replacement of one nucleotide in DNA with another nucleotide, it can also be described as a *nucleotide substitution mutation.* If a nucleotide substitution in DNA results in replacement of one amino acid with another in a protein, it can also be described as a *missense mutation.*