Evolution - DNA Mutations Flashcards
Missense Mutaiton
A change in DNA resulting in different amino acids being encoded at specific positions in the resulting protein.
Point Mutaitons
The change of a single nucleotide
Indels
Insertions/Deletions of nucleotides into genomic DNA
Transposable Elements
NA sequences that can change position within the genome, altering cell identiy and genome size
Inversions
Where segments of the chromosome break off and reattach in the reverse direction
How large can Transposable Elements be?
100 to 10,000 BP
Retrotansposons
TE replication through reverse transcription of an RNA copy and integration product DNA into new sites of the host.
DNA transposons
Small DNA strands that can move from one place of the genome to another.
Knockout Mutation
A permanent stoppage of gene expression.
What are the two types of Transposable Elements?
Retrotransposons and DNA Transposons
Where do Transposable Elements occur?
Mostly in non essential genomic regions
Frameshift Mutation
Those in which indels are in numbers not multiples of threes
What does a frameshift mutation mean for the gene of which it is in?
The expressed protein will be non-functional due to changes in amino acid sequence.
Anticipation
Genetic conditions becoming more severe and appearing earlier as disorder is passed through generations.
What causes increased Anticipation?
Increased numbers of tandem repeats
Replication Slippage
Where DNA strands misallign during replication of repeated DNA sequences.
What is the process of Replication Slippage?
Replication strand synthesis, complex disassciates then reassociaties, 3’ of strand reanneals to template, pairing with upstream set of repeats.
What causes expansion in Replication Slippage?
Different number of repeats between daughter and template strand, nucleotide excision repair system introduces expanded region into template strand.
What causes FMR1 inactivation?
Methyl group addition to cytosine NT in 5’ region of the FMR1 gene, repressing gene at high densities.
G Quartet
Four Guanine residues forming a ring like structure where each NA is both a donor and acceptor for hydrogen bonds
FMRP
Transports mRNA molecules in synapses and regulates local translation.
AMPA receptors
Responsible for bulk of synaptic transmission through CNS.
How does FMRP relate to AMPA?
FMRP regulates translation of mRNA movement at synpases, like AMPA.
What is an example of a frameshift mutations?
Cystic Fibrosis, cronhs disease and many cancers
CF Transmembrane Conductance Regulator
Helps in maintenance of balance of salt and water on surfaces in the body like the lung.
Minor Allel Frequency
The Frequency of which the second most common allele occurs in a population.
What are the most frequent mutations?
Single NT variants like SNP or SNV.
Dynamic Mutations
Unstable heritable elements where expression probability is a function of number of copies of the mutations, thus progeny has different mutation likelihood than predecessor.
What is an example of a dynamic mutation
FMR1 mRNA trinucleotide repeat expansions silence promoters at 55-200 CGG-CCG repeats.
What repeats can undergo expansion?
Trinucleotide repeats, microsattelites and minisattelites
Sherman Paradox
The incidence of fragile X can increase with subsequent populations, where X chromosomes duplicate, the triplet CGG is repeated again and again.
What is the average amount of repeats in the FMR1 gene?
30 in humans
What are examples of diseases caused by dynamic mutations?
Huntingtons, spinal-bulbar muscular atrophy
What are tandem repeats most often caused by?
Strand-slippage replication
What diseases are tandem repeats associated with?
Neurodegenerative diseases
How much of the entire genome is tandem repeats?
3%, 8% of this being in coding regions.
What are hypothetical functions of tandem repeats?
Bacteria as contingency genes allowing pre-emptive mutational events to improve microbial survival.
What do contingency genes do in bacteria?
Cause frameshift mutations to express different proteins that may assist in avoidance of immune systems.
What genes can STRs assist in?
PIG3 gene
Tyrosine Hydroxylase
Epidermal Growth Factor
Tyrosine Hydroxylase
This synthesise dopamine from glutamine
What is the mutation rate of STR?
10^-2 nt per generation.
What are the potential causes of mutation of STR?
Homologous chromosomes crossover in meiosis, retrotransciprt STR synthesised A-rich STRS a function of retro transcription but probably polymerase slippage.
What are kinds of mutation?
Germline vs Somatic
Point Mutations
Spontaneous vs Induced
What mays can mutations occur?
Change in gene position/number or nucleotide sequences
Somatic Mutations
These are not passed onto offspring, on from all cells derived from the original mutaiton
How much cancer caused by somatic mutations?
85%
Germ-line Mutations
Passed onto offspring causing inherited genetic disease being natural selection basis
What is an EG of base pair mutation?
Sickle Cell Anemia
What is Sickle Cell based on?
Adenine replaced by a thymine in the HBB gene resulting in codon change from glutamic acid to valine
Why does Haemoglobin S cause SCA?
Cannot polymerise forming sickle chape with beta globin altered and blood vessel blockage by RBC conglomeration
What causes spontaneous mutation?
DNA replicaiton like base tautomerism
What is an example of spontaneous mutation?
Nucleotidal change to isomeric or tautomeric conformations
Why is tautomerism significant?
As DNA structures exist primarily in one tautomeric form, that being the keto form
What might cause SNP?
Slippage with DNA secondary structures where misallignment with template result in NT addition
What may cause Induced mutations?
Chemical
Physical
What are the types of Chemical modificaitons?
Checmical resembling DNA bases pairing incorrently when incorporated
Deamination
Hydrocarbon addition to NT base
How may 5 BromoUracil cause mutation?
Incorporates though it was thymine rearranging to resemble cytosine being a base analogue
Base Analogue
These are molecuels that can substitue for normal bases in nucleic acids
What does mutatability of 5BU derive from?
Ability to nudergo tautomeric shifts converting from keto to enol forms
What is the most common form of deamination?
Cytosine to Uracil with DNA replication mispairing, resulting in A insertion instea dof C
Alkylating Agents
These are compounds reacting with electron-rich atoms in biological molecuiels to form covalent bonds
What derives Alkylating Agents capacity to mutate?
High electrophilicity allowing reacting to nucleophiles
Where do alkylating agents nuclephilically attack?
Nitrogen/Oxygen present in DNA bases with alkyl group transfer
What is the most common chemical modificaiton?
Methyl/Ethyl group additiosn to N7 of guanine
Ethyl Methanosulfonate
This is a mutagenic, teratogenic and carcinogenic agent
Intercalating Agents
These are hydrophobic, heterocyclic ring molecules resembling ring structures of base pairs
What is an example of a Intercalating Agent?
Ethiidium Bromide causing frameshift mutations
What does ionizsing radiation derive from?
High energy particles like X-ray, Gamma rays and alpha-beta particles
What does ionising radiaiton form?
ROS of hydroxyl radicals and superoxide radicals
What does UV radiation result in?
Pyrimidine dimer formation by UV-B radiation
How does UV light exert its effects?
Promote electrons to higher energy states
How many pyrimidine dimers be repaired?
Nucleotide Excision Repair Pathway
What does NER deficiency result in?
Xeroderma Pigmentosum
How can carcinogens be identifed?
Ames Test
Ames Test
This is a bacterial short-term test for indetificaiton of carcinogens using mutagenicicty in bacteria as an endppint
