y5 bio: cluster 3 (mutations and gene editing)

what is a gene mutation?

a permanent structural change to the DNA base sequence in a gene

when do gene mutations normally occur?

errors in base pairing during DNA replication (main enzyme: DNA polymerase III) are the most common origin of mutations

what is an insertion mutation?

the addition of one or more extra nucleotide bases into a DNA sequence, frameshift risk

what is a deletion mutation?

the removal of one or more nucleotide bases from a DNA sequence, frameshift risk

how does a frameshift mutation alter gene expression?

insertions or deletions not in multiples of three shift the reading frame, altering all downstream codons and amino acids

what happens during a base substitution mutation?

one single nucleotide base is replaced by another base in the DNA sequence, reading frame intact (C to T and A to G transitions most common)

what are the 3 possible impacts on phenotypes?

neutral (no effect on phenotype), deleterious (harmful), beneficial (far rarer than neutral and deleterious)

what defines a silent mutation?

a mutation that alters a codon but still codes for the same amino acid due to code degeneracy

what occurs during a missense mutation?

a mutation that changes a codon to code for a different amino acid, altering protein structure

what is a nonsense mutation?

a mutation that accidentally creates a premature stop codon, producing a truncated, non-functional protein (note: it normally has deleterious effect, but if it happens at the near end of the protein, it’s neutral effect)

what specific DNA mutation causes sickle cell anaemia?

a base substitution in the HbA gene changing the codon from GAG to GTG (Glu to Val)

what is a point mutation?

a mutation that alters, inserts, or deletes a SINGLE base pair in the DNA sequence

which base in amino acid can be changed and still code for the same amino acid?

third base, its called a mobile base!

what are SNPs (yes again….from inheritance…)?

single nucleotide polymorphisms, where base substitution is inherited by >1% of population. only neutral or beneficial substitutions stay, harmful ones are selected out

do SNPs change amino acid sequence?

NO! they are silent at protein level, due to degeneracy of genetic code

are SNPs of importance?

YES! they support ancestry testing and personalised drug dosing

what are the causes of gene mutations?

spontaneous errors OR induced mutagens

what is the difference between spontaneous errors?

they occur naturally from background replication errors, made during DNA replication (DNA polymerases do proof reading but some mistakes slip through)

what is an induced mutagen?

a physical or chemical agent that increases the rate of mutations above background levels, examples include chemical mutagens and high level radiation

examples of chemical mutagens?

nitrosamines (found in tobacco smoke), mustard gas (cross link DNA strands), benzene (forms DNA adducts)

examples of high level radiation

UV/gamma rays (breaks phosphodiester bonds), radon gas (source of X-ray exposure)

what is DNA transversion?

type of point mutation where two ring purine base is swapped for one ring pyrimidine base or vice versa

what is DNA transition?

specific type of point mutation where a purine/pyramidine replaces another purine/pyramidine (A for G) or (C for T)

what is DNA hotspot?

region of genome that is highly prone to genetic alteration or DNA damage

what is the difference between a somatic mutation and a germ cell mutation?

somatic mutations occur in body cells, not gametes and and cannot be inherited

potential danger of somatic mutation

when carcinogens enters somatic cells, they cause mutations in proto-oncogenes or tumor suppressor genes, disrupting cell cycle regulation. and if there are MULTIPLE somatic mutations in cell-cycle control genes, there will be uncontrolled cell division and if it forms a tumor…and if it's malignant - CANCER.

why is it so hard to treat inherited gene disease?

due to germ line mutation, the fertilised zygote carries the mutation and every cell derived from zygote by mitosis will inherit the mutation and mutation is now present in all cells…

what are the sources of genetic variation that produce new COMBINATIONS of alleles?

random mating, random fertilisation, crossing over, independent assortment

why are gene mutations impt for genetic variance?

mutations created every allele in existence, no joke. they are the only mechanism that generates new genetic info

why are gene mutations impt for natural selection?

without mutation -> no new alleles arise -> no genetic variation -> natural selection has nothing to act on -> evolution stops

gene mutations are (____) on indiv level but (____) on species level

good, bad

what is gene knockout technology?

silencing a gene to reveal its function, so can prevent gene from spreading diseases

CRISPR Cas 9 real world application?

GABA is a neurotransmitter linked to reducing blood pressure and relaxation! and they normally convert to glutamate during ripening via an enzyme…SO. people have used CRISPR Cas9 to inactivate this enzyme gene, so GABA persists at 4 to 5x higher conc in ripe fruit

CRISPR Cas9 ethical considerations

genetic equity (super $$, so is it only rich get to do it?) and designer babies (slippery slope from cutting diseases to selecting preferred traits)

what is the difference between a conserved and a highly conserved sequence + examples?

conserved: similar sequences across related species, tolerates minor tweaks (e.g., standard metabolic enzymes) highly conserved: near-identical sequences across vastly different species, zero mutation tolerance because changes are lethal (e.g., TATA box, histone proteins)