Genetic variation in disease Flashcards Preview

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Flashcards in Genetic variation in disease Deck (28)
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1
Q

DNA packaging

A

heterochromatin
euchromatin
histones
looping structure

2
Q

Start codon

A

AUG
encodes methianine
starts translation of all proteins

3
Q

stop codon

A

3 codons stop protein translation

4
Q

what are the types of DNA change?

A

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

5
Q

single base substitutions

A

SNPs

replacement of a single nucleotide by another

6
Q

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

A

synonymous/ silent variation and non-synonymous mutations

7
Q

synonymous variation

A

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

8
Q

non-synonymous mutations

A

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

9
Q

different types of mutations

A

silent
missense
nonsense

10
Q

silent mutation

A

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)

11
Q

Nonsense mutation

A

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 .

12
Q

Nonsense mediated decay

A

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

13
Q

stop codons

A

UAG
UAA
UGA

14
Q

Missense mutations

A

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

15
Q

Non-conservative substitution

A

gross reduction or complete loss of biological activity

qualitative changes in the function of the protein may occur

16
Q

what are the types of missense mutations?

A

non-conservative and conservative

17
Q

conservative substitution

A

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

18
Q

frameshift mutations

A

insertion or deletion

19
Q

what happens when there is a frameshift mutation?

A

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

20
Q

variant

A

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

21
Q

mutation

A

rare variant in DNA sequence - disease causing

22
Q

polymorphism

A

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

23
Q

what are the CFTR mutations?

A

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

24
Q

p.Gly542Ter (stop)

A

unstable mRNA, protein not made

25
Q

p.Gly551Asp

A

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

26
Q

p. Phe508del

A

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

27
Q

p.Ala455Glu

A

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

28
Q

p.Arg347Pro

A

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