Causes of genetic mutations Flashcards
what is a mutation?
germline vs somatic mutation?
mutation: sudden change in genetic trait. drives allelic variation
somatic: mutation occurs first in the person.
germline: mutation is passed down from one generation to next
somatic mutations can turn into germline mutations
how can you classify types of mutations? explain each type (3)
at scale of mutation:
1. genomic change: whole chromosome gain / loss
2. chromosomal change: result from rearrangement of genetic material and give rise to visible structural changes in chr.
- gene mutation: vast majority are single base pair changes / small number of base pair changes
what are point mutations?
what are the differnent mutations that are consequences of point mutations(4)?
point mutations: change in single base pair mutations. occur in DNA replication errors. most common mutation. substitution, insertion, deletion or inversion of base pairs.
consequences:
a) silent mutation - no change to a.a. sequence
b) missense mutation: changes one a.a. to another (conservative: swaps for a.a. with similar properties, non-conservative: swaps for a.a. with dissimilar properties)
c) Nonsense mutation: creates an early stop codon (creates shorter a.a. highly damaging)
d) frameshift: due to deletion or insertion shifts entire coding sequence by one or more bases due to deletion or insertion of bases
what is a framework mutation?
single base is inserted or deleted -> whole reading sequence of a.a. is shifted
name the regions of non-coding DNA that can still affect resulting a.a. sequence
- regulatory region
- splice site
- UTR
- intergenic regions
what is the change that occurs in Hb S?
Single base mutation of Adenine to Thymine. Produces a substitution of valine for glutamic acid at the sixth codon of the beta-globin chain. Hb gene found on chromosome 11
what causes the differences in CF?
which is the most common deletetion in CF?
numerous mutations found in CF, causing differences in CFTR.
BUT: different severity of CF disease arise from severity of effect of the mutation of CFTR protein. (most to least: Type 1 -> Type 6)
most common mutation: phenylalanine 508 deletion (deletion of CTT: frameshift mutation = less stable protein)
give an example of disease caused by a frameshift mutation
Tay-Sachs disease
- autosomal recessive disease
- stops nerves working and is usually fatal
- mutation in Hex-A gene
- mutations: 6 deletions, 2 insertions
in Ashkenzai Jew pop: get 4 base pair insertion in exon 11
what are the different types of chromosomal mutations?
deletion, duplication (part of a chr breaks off and attaches to sister chromatid), inversions (part of a chr breaks off and reinserts backwards), insertions (part of one getes inserted to another chr), translocation (part of chr breaks off and attaches to different chr)
name two diseaese / disorders from chromosomal mutations?
1. Y - chromosome infert: deletetion part of Y-chromsome. called azoospermia factor (AZF) A, B or C
2. Charcot-Marie-Tooth disease (CMT1A): duplication of regions of chr 17. progressive loss of neurons
what are non-disjunction diseases?
Nondisjunction means that a pair of homologous chromosomes has failed to separate or segregate at anaphase so that both chromosomes of the pair pass to the same daughter cell.
lead to:
gain or loss of whole chromosomes. e.g. Down Syndrome: trisomy
what causes genetic mutations?
spontaneous mutations
induced (environmental) mutations (e.g. radiation, chemicals, infectious agents)
what are someo of the different mechanisms of spontaneous mutations?
1. tautomeric shift (base substitution)
2. depurination
3. deamination
(4. errors in proof reading
5. depyrimidation (very low occurance)
6. oxidation )
what are tautomers?
tautomers: all DNA bases (CTAG) have different forms depending on their position on the atoms
- common form of of bases are amino (C&A) and keto (G & T) forms. But sometimes can get rare form of base pairs: imino (C’ & A’) and enol (G’ & T’).
- (C’ binds with A, T’ binds with G, A’ binds with C, G’ binds with T)
what is a tautomeric shift?
- what is the number of a) wild types b) mutants of the DNA exist that occur after second generation progeny after a tautomeric shift?
tautomeric shift:
- when a tautomer occurs in DNA replication, the imino or enol pairs with non-complementary base -> base sub
- BUT: after the first DNAreplication occurs, the BP that was a tautomer reverts back to its stable form. HOWEVER, the the other non-complementary BP stays! (the mutation)
result: in 3x wild type, 1 mutant. transition mutation. means can go undetected as shape of protein doesnt really change
what is depurination mutation?
- loss of a purine base (A or G)
- leads to deletion mutation
(can occur in double DNA helix)
what is a deamination mutation?
- removal of the amino (-NH3) group through hydrolysis water
- leads to substitution reaction
how does UV radiation cause direct mutations?
direct damage
- cause DNA phoshpate backbone to break
- break BP connections
- alter bases
- cause intra-/inter- stand cross links
how does UV radiation cause indirect mutations?
indirect effects: ionizing radiation creates free radicals that damage DNA by reacting with it
what is the effect of DNA damage by UV radiation to melanocytes?
in melanocytes: pyrimindine dimers -> formed when cyclobutane rings occur between adjacent, same strand pyrimidines in DNA
- (disrupts p53 gene (tumour supressor))
