Lec 5-1 Flashcards
Mutations are
Changes in DNA sequence
Inheritable by cells or organisms
Importance of mutations
Necessary for evolution (source of genetic evolution)
Cause of many diseases and disorders
Cannot have one without the other
Two basic classes of mutations
Somatic
Germ-line (most common)
Gene mutations
Mutations that affect a single gene
Base substitutions
Insertions and deletions expanding nucleotide repeats
Types of base substitutions
Transition (common-changing a purine to another purine or a pyrimidine to another pyrimidine)
Transversion (more possibilities- switches a purine into a pyrimidine or vise versa)
Causes of base substitutions
Spontaneous replication errors
Spontaneous chemical changes
Mutagens
Base substitutions may
Alter one codon
Tautomers
Distinct forms each base can have depending on position of hydrogen (proton)
Tautomeric shift
When hydrogen (proton) shifts to another position creating a new tautomer form
Base substitutions
Spontaneous chemical changes
Depurination-Loss of a purine
Deamination-Loss of amino group
Usually result in incorrect base substitutions
Depurination
Covalent bond between purine and sugar backbone is broken
Loss of a purine creates
An apurinic site (a wrong base is added to replace the purine)
Deamination
Loss of an amino group (NH2) from a base
Converts the base pair into a uracil
Replication treats it like a thymine and binds it to an adenine
Insertions and deletions
Addition or removal of one or more nucleotide pairs
Insertion and deletion causes
Strand slippage
Unequal crossing over
Insertion and deletion
Strand slippage
Occurs when one DNA strand forms a small loop
Results in the additions of one nucleotide on the new strand
Expanding nucleotide repeats
Set of nucleotides that increase in copy number
Causes numerous diseases such as ALS
Expanding nucleotide repeats
Number of copies correlates with
Severity of disease
Age of onset
Instability
Cause of expanding nucleotide repeats
Repeats lead to a hairpin being synthesized
New extensive strand serves as a template
Base substitutions can cause
Missense (makes a different amino acid)
Nonsense (creates a stop codon as the triplet does not code for any amino acid)
Silent mutations (caused by altering the last base of a triplet. Does not change the protein sequence)
Insertions or deletions can cause
Frameshift mutations
In-frame mutations
Types of effects on protein function and phenotypes
Loss of function mutation
Gain of function mutation
Conditional mutation
Lethal mutation
Loss of function mutations
Partial or complete absence of gene product function
Usually recessive- requires two copies to see a phenotype
Gain of function mutation
Gene product has a new function
Usually dominant- one copy produces a phenotype
Conditional mutation
Phenotype seen under certain conditions (eg. elevated temp)
Lethal mutation
Causes premature death
Forward mutation
Original mutation changing phenotype away from wild type
Reverse mutation
A second mutation that reverses the original mutation site back and returns phenotype back to wild-type
Suppressor mutation
A second mutation that reverses the phenotype back to wild-type, but through mutating a different site in the DNA
Suppressor mutation types
Intragenic
Intergenic
Intragenic mutation
In the same gene as original mutation being supressed
Intergenic mutation
In a different gene as the original mutation
Can also occur through interactions of two genes functioning in the same protein complex
