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Flashcards in G8 Deck (32):
1

describe an autosomal dominant inheritance and and give an example

half of offspring affected
unaffected individual doesnt transmit disease
eg. Anchroplasia - dwarfism

2

describe an autosomal recessive inheritance and give an example

ussually only one generation affected
if both parents carriers = 1/4 affect, 1/2 carries, 1/4 not affects
eg. CF

3

What is X linked recessive inheritance and give an example

carrier females transmit disease to half their sons and carrier status to half their daughters
eg. X linked haemophilia

4

c.76A>T

substitution A->T in coding DNA

5

c.76_78delACT

range of affected resieus 76-78 by deletion of ACT

6

c.76dupA

duplication at 76 of A base

7

c.76delA

deletion at 76 of A

8

c.76-83inv

inversion between 76 and 83

9

c.76_77insG

insertion but it duplication describe as duplication
G inserted between 76 adn 77

10

p:Lys76Asn

p refers to primary translation product
at AA 76 varient results in sub of asparagine instead of normal lysine

11

p.Tyr356X

X indicates a nonsense codon has been generated

12

c.1408+2T>G

second nucleotide after c.1408 that would normally be the invariant T of splice site is insead a G

13

c.789-1G>A

first nucletodie before c.780 that would normally be invariant G of splice site is now an A

14

c.69_71del(p.Val15del)

in frsame deletion deletes aa valine

15

c.546insA(p.Val170fs)

out of frame insertion inserted valine causing frameshift after 170

16

what letters denote each type of reference seqeunce

c= coding DNA
g- genomic DNA
r = coding RNA reference seq
n = non coding RNA ref seq
m = mitochondrial DNA seq

17

What is HGVS

human genome variation society

18

what terms do HGVS use to prevent confusion from using terms like SNP or mutation

sequence variatn
alteration
allelic variant

19

what classes and terms do HGVS use to recognise that some variants can be harmful

5 = affects function
4 = probs affects function
3 = unknown
2- probs doesnt affect function
1= doesnt affect function

20

what casues anchrondoplasia

Fibroblast growth factor receptor 3 p FGFR3 - represses ossification of chondrocytes that proliferate and mature into bones at growth plate
- in anchondroplasia ossification is further pressed

21

what is ossification

process where catilage is turned into bone

22

why is it difficult to predict what the ouctome of splice site mutations will be?

as genes use alternate transcriptional start sites, alternate combos of exons, althhough usually one isoform RNA is shown, cell can produce several different ones at the same time and this remains poorly understood

23

what is nonsense mediated decay?

highly conserved quality control survelliance mechanism
recongises and degrades defective mRNAs with premature termination codons PTCs which if translated could produce harmful aberrant proteins
(can occur indep of any DNA mutations as a result of errors during transcription, processing or packaging)

24

what happens to EJCs in normal splicing and i PTC containing mRNA

normal: proteins of exon junction complec = deposited 2-24 nts upstream of each exon/exon unction, and are displaced by scanning ribosome during inital round of translation.
PTC: upon recognition of stop codon, a termination complex is fomred, in PTC containing mRNA, EJCS downstream of PCR are not displaced allowing the termination complex to interact with the EJC triggering NMD.

25

why do premature stop codons lead to

not neccessarily truncated proteins = often no protein at all through NMD

26

What could PTC read through do?

override NMD degradation mechanisms and allow some proteins to be produced from mutant mRNAs - pioneered in the field of DMD
= clinical practice

27

what do most cases of CF result from

phe580del
change in F508, 3nt deletion, deleting phenylalanine at position 508. created a misfolded protein which is usually degraded in ER, poorly function if does reach cell surface.

28

what kind of mutation is DMD usually caused by

frameshift and nonsense mutations

29

what kind of mutation is backer muscular dystrophy caused by

inframe deletion or change in expression

30

how is it theoretically possible to convert faulty mRNA to produce product

inducing exon skips using antisense constructs and produce an inframe mutation without the framshift nonsense codon

31

what can inframe deletions be

1. disease causing as in CFTR - Phe508
2. better than no protein at all as in dystrophin
3. tolerated with no apaprent ill effect (as heterozygote)

32

Describe the case study of the mutation on ENG

endoglin gene (ENG) causing HHT - autosomal dominant disease causing nosebleeds and abnormal blood vessels, only 2/3 children had HHT = not possible, so found that it was just an endoglin missense polymorphism that had been overinterpreted, seqeunce change was not in pahse with true diesease causing gene.