Mutations Flashcards
What is exogenous DNA damage?
radiation, free radicals (uncharged mol with unpaired valency electron), chemicals, anti-cancer –> defective DNA repair –> MUTATION
What is endogenous DNA damage?
DNA replication defects, transposable elements –> defective DNA repair –> MUTATION
What are the 3 types of mutation on a micro level?
Deletion –> shorten = frame shift -1, can affect stop codon being read.
Insertion –> lengthen = frame shift = +1, can affect stop codon being read.
Substitution (missense) (nonsense = changed bp = becomes stop codon) –> change one for another: transition or transversion
Define transition vs transversion
Transition –> purine to purine (A-G), pyrimidine to pyrimidine (T-C).
Transversion –> purine to pyrimidine or vice versa (A/G – C/T)
What are the 5 types of mutation on a macro level?
Deletion –> a section removed.
Duplication –> a section duplicated.
Inversion –> a section flipped.
Substitution –> one section taken from one chromosome and added to another.
Translocation –> 1 piece on each chromosome swapped
What is a synonymous mutation?
CHANGES MAY NOT ALWAYS HAVE AN EFFECT –> codes for same AA = neutral/silent, synonymous
Describe what a frameshift mutation is
Deletion –> shorten = frame shift -1, can affect stop codon being read. Insertion –> lengthen = frame shift = +1, can affect stop codon being read,
What is the difference between a missense mutation and a nonsense mutation?
Missense: substitute nt = becomes another AA, nonsense: substitute nt = become stop codon
Outline the sickle cell mutation
Mutation in codon 7, 6th AA. Glu –> Val. Base substitution mutation
What do mutations result from?
Errors in cell division, Ionising radiation, Chemicals, Viruses
What is a spontaneous mutation?
germ line (first affected person)/somatic, if autosomal dominant and parent not affected = must be spontaneous, autosomal recessive mutation of same gene both chromosome = highly unlikely. Spontaneous mutation = heterozygote
What is a germ line mutation?
eggs/sperm, affect all cells in body, passed on
What is a somatic mutation?
body cell, not passed on, error in mitosis, can be genetic (DNA replication error) or chromosomal
Describe mitochondrial mutations
often involve multiple organ systems, prominent in organs requiring a lot of energy (heart, brain, muscles), maternal inheritance
Somatic: limited ability to repair, mutations build up over time, may play a role in normal ageing, cancer.
Germ line: associated with defects in oxidative energy metabolism
What happens in a cell with 2 copies of the same chromosome?
increase in expression of gene, if genes slow growth = fatal, if genes promote growth = grow uncontrollably = cancer
Outline PGCs (Primordial Germ Cells) in female devel
PGCs arrive at ovary, diff into oogonia, undergo further mitosis, some enter prophase meiosis 1, arrest cell cycle = primary oocyte (surrounded by flattened epithelial = primordial follicle)
Describe PGCs (Primordial Germ Cells) in male devel
PGCs arrive in testis, stay there until puberty. Puberty = spermatogonia diff to spermatozoa
What are PGCs?
Primordial Germ Cells
Why is the mutation rate higher in male gametes?
no. divisions higher then female gametes
What is Aneuploidy?
presence of an abnormal number of chromosomes in a cell
What happens to a foetus exposed to radiation?
death/aborted, teratogenesis (process by which congenital malformations are produced in an embryo or foetus) cancer when born
What features would allow a germ cell mutation to be inheritable?
It would not be lethal to the gamete, It would not impair gamete function, It would not be lethal at fertilisation, It would allow the production of a viable adult with normal reproductive capacity
What effect can mutations have on drug treatment?
mutation may lead to no effect of the drug, reduced effect, increased effect, side effects or an allergic reaction
Describe loss of function vs gain of function in regard to mutations
In general recessive mutations cause loss of function and often affect biochemical pathways
In general dominant mutations cause increased function and often cause structural abnormalities
