Mutations and DNA damage
Mutations are random but their are hotspots in the genome
Suppressor mutations = cancel out effect of another mutation
Back mutation : reverted back to wild type
Individuals carry an average of 1/2 lethal recessive genes
Classification
Origin
Spontaneous - absence of known mutagen so due to errors in DNA replication
Induced - presence of mutagen (agent known to increase rate of mutation)
Cell type
Somatic - not inherited by offspring
Germline - inherited by offspring
Expression
Unconditional - always
Conditional - only in specific environment eg temp
Effect on function
Loss of function
Gain of function / ectopic eg. wrong stage in development or in wrong cell
Hypomorphic / leaky
Hypermorphic
Effect on translation
Missence = non synonymous amino acid
Neutral- non synonymous amino acid but has same/ similar function
Silent = synonymous amino acid
Examples of mutation
Sickle cell anaemia
missence
A to T Glu to Val
Beta globlin gene
Beta Thalassemia
Frameshift
Deletion of AA
Beta globlin gene
Causes of mutation
Base substitution due to different tautomeric forms
Imino A Amino C
Enol T + Keto G
Imino C + Amino A
Enol G + Keto T
Errors in DNA replication
Spontaneous DNA damage
Oxidative damage
Deletions and insertions cause frame shifts and new strand shifts out alignment
Oxidative deamination
Methyl C to T
A to Hypoxanthine
C to U
G to xanthine
Base loss
hydrolysis of phosphodiester bond opposite A base on other strand leaves abasic site
Reactive oxygen species (ROS) such as a singlet O or hydrogen peroxide
Cells scavenge it nut it damages DNA by changing bases and breaking strands
Methylation
A to methyladenine 3 blocks replications
Induced DNA damage
UV light
Formation of pyrimidine dimers (bond between to adjacent pyrimidine bases) blocks transcription
Ionising radiation
Generates ROS
Nitrous acid
deamination
Base analogues
Base adducts
Alkylating agents such as cigarettes link the 2 strands of DNA so helicase cant work
ADD chemical groups to bases
Aflatoxins (food stuff) cause base loss