19: Mutations & DNA Repair

What is the start for all genetic variation

Mutations

Point mutation

Change in a single base pair

Transition point mutation

Mutation that is a change from purine to purine or pyrimidine to pyrimidine

Transversion point mutation

Mutation that is a change from purine to pyrimidine

Indel mutation

Insertion or deletion

Silent mutation

No change in the AA coded for

Missense mutation

Base sub that changes the AA coded for

Neutral missense mutation

Changed protein has the same fitness

Nonsense mutation

Premature stop codon

Frameshift mutation

Any ± not in a multiple of 3

Result of up promoter mutations

Increased transcription

Result of down promoter mutations

Decreased transcription

Most prevalent form of a gene

Wild type

Reverse mutation

Takes mutant to wild type form

Deleterious mutation

One that decreases the chances of survival

Conditional phenotype

One that is only seen in certain environments

Suppressor mutations

Reverse the phenotypic effects of another mutation

Intragenic suppressor

Suppressor mutation that acts within the same gene as the primary mutation

Intergenic suppressor

Suppressor mutation that acts in a different gene as the primary mutation

Redundant function mutation

Mutation that results in a gain of function that covers up the loss of function from the primary mutation

Common pathway mutation

The primary and secondary mutations happen in the same pathway

Multimeric mutation

Mutation on a different polypeptide but in the same multimeric protein as the primary mutation

Types of mutations that alter chromosome structure

Rearrangement, breakage, translocation

Somatic cells

Everything but germ cells

Germ cells

Give rise to gametes

Evolutionarily, mutations where are the only ones that matter

Germ line mutations

How does mosaicism happen

Early somatic mutations

Three ways for spontaneous mutations

• Depurination

• Deamination

• Tautomeric shift

Depurination mutation

Removal of a purine, and during the repair of the abasic site, there is no template, and so there is a 75% rate of mutation

Deamination mutation

Removal of an -NH₂ from cytosine, turning it into a uracil (or a 5meCytosine to a thymine). This is not compatible with DNA, and if it isn’t repaired the mismatch is changed to AT during replication

Tautomeric shift

Shift of T or G from keto to enol, or shift of A or C from amino to imino. The enol and imino forms are less stable, which can cause mistakes in base pairing

How does ROS cause mutations

Oxidative stress

How do trinucleotide repeats cause diseases

The repeats can form secondary structure or extra methylation sites