DNA Mutation

what are genetic disorders caused by

abnormalities in one or more genes

• cycstic fibrosis, albanism, dwarfism (all issues w one gene)

Locus

a specific, fixed location of the allele

• a nucleotide position

• genetic marker

• gene

Genotype

genetic makeup of (part of) an individual

Phenotype

a measurable trait in an organism, often the consequence of a genetic variation

Mutation

a change that occurs in the DNA sequence, either due to mistakes when the DNA is copied or as the result of environmental exposure

impact:

• can range from no change in phenotype to big change in phenotype

Gene mutation and cause

a change to one or more genes - can lead to genetic disorders or illnesses

cause

• change in one or more nucleotides of DNA

• a change in many genes

• a loss of one or more genes

• rearrangement of genes or whole chromosomes

Single Nucleotide Polymorphism (SNP)

a common genetic variation when a single nucleotide (ex. A, T, C, or G) is altered and kept through heredity

• SNP: larger than 1% of population has single DNA base variation found

• mutation: smaller than 1% single DNA base variation

Effect of mutation (3)

• Silent mutation: codes for functional protein

• loss of function mutation: codes for a nonfunctional protein

• Gain of function mutation: codes for a protein with new function

Somatic mutations

• occur in a single body cell and cannot be inherited (only tissues deriving from mutated cell are affected)

Germline mutations

• occur in gametes and can be passed onto offspring (every cell in the entire organism will be affected)

Point mutation

a change in one base in the DNA sequence

main causes

• base substitution

• frame shift

types of mutations

silent: does not change amino acid, but in some cases can still have a phenotyping effect (ex. speeding up/slowing down protein synthesis, or by affecting splicing)

nonsense: changes an amino acid to a STOP codon, premature termination of translation

missense: changes one amino acid to another

• conservative: small impact

• nonconservative: large impact

Frameshift: deletion or insertion of a number of bases that is not a multple of 3. usually introduces premature STOP codons in addition to lots of amino acid changes

Substitution

when one or more bases in the sequence is replaced with different ones

Inversion

when a segment of a chromosome is reversed end to end

Frameshift mutation

• insertion: when a base is added to the sequence

• deletion: when a base is deleted from the sequence

How mutations occur (4)

• the environment

• chemicals

• spontaneous

• Deamination

Mutations and the environment

• DNA interacts w the environment and that interaction can be detrimental to its genetic information

  • UV-generated mutation involves the hydrolysis of a cytosine base to a hydrate form, causing the base to mispair with adenine during the next round of replication and ultimately be replaced by thymine

Mutations caused by chemicals

• oxidizing agents, commonly known as free radicals, are substances that can chemically modify nucleotides in ways that alter their base-pairing capabilities

  • ex. dioxin intercalates between base pairs, disturbing the integrity of the DNA helix and predisposing that site to insertions or deletions

Spontaneous Mutations

• mutations can occur spontaneously

  • depurination, in which a purine base is lost from a nucleotide through hydrolysis even though the sugar back bone is unaltered, can occur without a specific impact from the environment

  • if uncorrected by DNA repair enzymes, depurination may result in the incorporation of an incorrect base during the next round of replication

Deamination

• removal of an amine group from a base may occur

• deamination of cytosine converts it to uracil, which will pair with adenine instead of guanine at the next replication, resulting in a base substitution

Radiation causes mutations

• UVlight causes a thymine dimer when two thymines are next to each other

• DNA bulges at T dimer

General knowledge of DNA repair systems (3)

• cells have enzyme systems to repair damaged DNA

• there are several categories of repair systems and they function during different parts of the cell cycle

• the repair systems are under genetic control and they too can undergo mutation

3 kinds of DNA repair systems (just names)

• Base-excision

• Nucleotide-excision

• Mismatch repair

Base-excision repair

• Special enzymes replace just the defective base

  • 1 snp out the defective base

  • 2 cut the DNA strand

  • 3 add correct nucleotide

  • ligate gap

presence of Uracil in DNA is a great example of this type

Nucleotide excision

• same as Base-excision repair but removes larger segments of DNA (10-100s of bases)

  • recognizes more varieties of damage

Mismatch repair

• special enzymes scan the DNA for bulky alterations in the DNA double helix

• These are normally caused by mismatched bases

  • ex. AG, AC, CT

• base pairs w incorrect hydrogen bonding cause distortions in the double helix. this system monitors distortions

• these are excised, DNA resynthesized, and ligated