GENO- sequence variation

Question 1

define synonymous mutation

Answer 1

silent mutation (nucleotide change) - no amino acid change

Question 2

define non- synonymous mutation

Answer 2

missense - base mutation which changes amino acid coded for - can be okay - can be pathogenic

nonsense- leads to premature stop codon being produced
impact is dependent on where the mutation is - protein can be degraded / made shorter (truncated)

Question 3

what is a frameshift vs non-frame shift mutation

Answer 3

a mutation which affects the reading frame
e.g., a deletion / addition of 1 base = frameshift
a deletion / addition of 3 bases - non-frameshift

Question 4

what is meant by a mutation that causes loss of function

Answer 4

reduced activity / decreased stability = hypomorph
complete loss of gene product = null allele - amorph

e.g., sickle cell anaemia, phenylketonuria, CF, Gaucher’s

one healthy copy is enough to produce enough protein for the individual to be healthy
recessive disorders

Question 5

what is meant by a mutation that causes haploinsufficiency

Answer 5

when a loss of one allele is sufficient to case a problem
gene dosage
full amount of protein is required

e.g., ehlers-danlos syndrome, MonoMac syndrome, CHARGE syndrome

Question 6

what is meant by a mutation that causes gain of function

Answer 6

increased levels of gene expression
new functions for protein products
mutant allele produced a mutant protein which is damaging to individual (unregulated)

e.g., achondroplasia - decreased bone mass by altered regulation of osteoblasts/ osteoclasts

dominant disease

Question 7

what is meant by a mutation that causes dominant negative

Answer 7

mutant allele produces gene product that interferes with the correct role
protein produce by mutant allele interferes with role of wildtype alleles

mutation in transx factor removes activation domain but still contain DNA binding domain so binds to DNA but cant trigger transcription - blocks wildtype from binding

mutation in protein that is functional as a dimer - lacks functional domain but keeps dimerization domain - forms a dimer with the wildtype protein but resulting dimer is non-functional

Question 8

define substitution in relation to genetic variants

Answer 8

a type of mutation where one nucleotide is switched for another

Question 9

define point mutation in relation to genetic variants

Answer 9

when a single base pair is added/ deleted or changed

Question 10

define single nucleotide variant in relation to genetic variants

Answer 10

general term for the change of a single nucleotide

Question 11

what are some errors in DNA replication that can lead to sequence variants

Answer 11

single base substitutions, deletions, insertions

can alter the reading frame leading to loss / gain of amino acids

Question 12

define germline mutations

Answer 12

affects the gametes and therefore can be inherited and passed down through the generations

Question 13

define somatic mutations

Answer 13

only affects non-germline cells therefore cannot be passed down