GEN: Contribution of genetic changes to human disease

Question 1

what is single nucleotide substitution?

Answer 1

straight substitution of one base for another

Question 2

what are the 2 types of single nucleotide substitution divisions?

Answer 2

• transition - base conserved (a → g or c → g), ie purines and pyrimidines stay as they are.
• transversion - base changes (a → t or g → c)

Question 3

how many more possible transversions are there than transition?

Answer 3

transitions are 2x more common as transversions even though theres more possible transversions as transitions

Question 4

what are deletions?

Answer 4

loss of single base or sequence block

Question 5

what are insertions?

Answer 5

insertion of a base/bases between two previously adjacent bases

Question 6

what is tandem duplication in insertion?

Answer 6

Question 7

what are inversions?

Answer 7

Question 8

what are translocations?

Answer 8

Question 9

what are the 3 effects of coding regions?

Answer 9

silent

missense

nonsense

4 silent, 4 missense, 1 nonsense

Question 10

what is a silent mutation

Answer 10

not affect protein directly but can affect splicing

Question 11

what is a missense mutation

Answer 11

Will cause a single amino acid change, whose affect may be neutral or harmful
(resulting in gain of function, or direct/indirect loss of function).

Question 12

what is a nonsense mutation

Answer 12

Will cause premature termination of the reading frame, resulting in a truncated protein or NMD.

Question 13

what is more important than the extent of the variant?

Answer 13

effect on reading frame

Question 14

what are the commenest consequences of variants in splice sites?

Answer 14

• exon skipping
• use of cryptic splice sites (exon or intron)
• intron retention (small introns only)
• combinations of above

Question 15

in large rearrangements what is the critical determinant of the effect?

Answer 15

whether or not the removal or insertion of exon(s) affects reading frame

Question 16

what are the two types of Muller’s Morphs?

Answer 16

• function loss
• function gain

Question 17

what are the 2 function loss mutations?

Answer 17

• amorph: complete loss of gene function
• hypomorph: partial loss of gene function

Question 18

what are the 3 functions gain mutations?

Answer 18

• hypermorph: increase in normal gene function
• antimorph: acts in opposition to normal gene activity
• neomorphic: dominant gain of gene function different to normal

Question 19

why do proteins lose the ability to perform normal functions?

Answer 19

1. little or no protein produced
2. unstable protein or inappropriately targetted and degraded
3. residue or domain essential for function missing or critically altered

Question 20

what are the ways that function loss alleles exhibit dominant inheritance forms?

Answer 20

Question 21

how do proteins gain functions?

Answer 21

1. loss of regulation
2. novel function

Question 22

what is regulation loss?

Answer 22

Question 23

what is novel function?

Answer 23

Question 24

what type of effect does the change of arg to stop have on the SIAT9 gene?

Answer 24

nonsense

Question 25

what does the SIAT9 gene encode?

Answer 25

GM3 synthase

^ this is a critical enzyme in synthesis of a- and b- series gangliosides for membrane stability

Question 26

difference between purines and pyrimidines

Answer 26

pyrimidines both have Y in them

Question 27

which nucleotides are double ring and single ringed, which causes double bonds and which cause triple bonds

Answer 27

T-A (double bonds)
G-C (triple bonds)

Question 28

“small” rearrangements (deletions, insertions, duplications, inversions) refer to
those whose effects are confined to a single _____ of a gene.

Answer 28

EXON

Question 29

what are 3 qays in which “loss of unction” alleles exhibit a DOMINANT form of inheritance

Answer 29

Question 30

what is infantile onset epilepsy caused by

Answer 30

GM3 synthase deficiency

GM3 is encoded for by SIAT9

its autosomal DOMINANT