Genetic variation in disease

Question 1

DNA packaging

Answer 1

heterochromatin
euchromatin
histones
looping structure

Question 2

Start codon

Answer 2

AUG
encodes methianine
starts translation of all proteins

Question 3

stop codon

Answer 3

3 codons stop protein translation

Question 4

what are the types of DNA change?

Answer 4

single base substitutions
deletions of 1 or more nucleotides
insertions of 1 or more nucleotides

Question 5

single base substitutions

Answer 5

SNPs

replacement of a single nucleotide by another

Question 6

what are the categories of effects of changes to DNA sequences?

Answer 6

synonymous/ silent variation and non-synonymous mutations

Question 7

synonymous variation

Answer 7

silent variation
no change to the amino acid sequence
no change in function
doesn’t cause disease

Question 8

non-synonymous mutations

Answer 8

changes amino acid sequence of protein
can change structure of protein
can change function of protein
can cause disease and normal variation

Question 9

different types of mutations

Answer 9

silent
missense
nonsense

Question 10

silent mutation

Answer 10

does not alter the polypeptide product of gene
often single base-pair substitution at 3rd position of a codon
degeneracy of genetic code will often result in another triplet that codes for same amino acid
no alteration in the properties of resulting protein
could be outside of the coding region - intron(ic region)

Question 11

Nonsense mutation

Answer 11

formation of stop codons causing premature termination of translation of a peptide chain . Premature stop codon may lead to expression of a truncated protein . BUT usually the mRNA is degraded by nonsense-mediated decay so no protein is made .

Question 12

Nonsense mediated decay

Answer 12

RNA surveillance that degrades faulty mRNA/ truncated mRNA which protects the body from possible consequences of truncated proteins interfering with normal function .

Question 13

stop codons

Answer 13

UAG
UAA
UGA

Question 14

Missense mutations

Answer 14

coding for a different amino acid
synthesis of an altered protein
if the new amino acid is chemically dissimilar the structure of the protein will be altered

Question 15

Non-conservative substitution

Answer 15

gross reduction or complete loss of biological activity

qualitative changes in the function of the protein may occur

Question 16

what are the types of missense mutations?

Answer 16

non-conservative and conservative

Question 17

conservative substitution

Answer 17

some single base pair substitutions result in replacement of a different amino acid that is chemically similar and so there is no or very little difference in the function

Question 18

frameshift mutations

Answer 18

insertion or deletion

Question 19

what happens when there is a frameshift mutation?

Answer 19

if a multiple of 3 nucleotides is not inserted or deleted the mutation will disrupt the reading frame so the amino acid sequence of the protein subsequent to the mutation bears no resemblance to the normal sequence
adversely effects function of the protein and usually results in a premature stop codon downstream to the mutation

Question 20

variant

Answer 20

used to describe an alteration that may be benign, pathogenic or of unknown significance . being used in place of mutation

Question 21

mutation

Answer 21

rare variant in DNA sequence - disease causing

Question 22

polymorphism

Answer 22

common variant in DNA sequence - benign - non disease causing . present in more than 1% of the population

Question 23

what are the CFTR mutations?

Answer 23

p. Gly542Ter (stop)
p. Gly551Asp
p. Phe508del
p. Ala455Glu
p. Arg347Pro

Question 24

p.Gly542Ter (stop)

Answer 24

unstable mRNA, protein not made

Question 25

p.Gly551Asp

Answer 25

protein reaches cell membrane but channel gate does not open and close. A potentiator drug may help

Question 26

p. Phe508del

Answer 26

Protein misfolded so can not reach cell membrane . Targeted for degradation . A corrector drug may help

Question 27

p.Ala455Glu

Answer 27

splicing errors mean insufficient protein is made . What is made gets to cell membrane and works properly . A potentiator drug may help .

Question 28

p.Arg347Pro

Answer 28

protein is made and moves to cell membrane, appropriate amounts made but channel doesn’t work properly . A potentiator may work .