Dalton - Genomic Testing in the NHS Flashcards Preview

MBB329 - Genetics of Human Disease > Dalton - Genomic Testing in the NHS > Flashcards

Flashcards in Dalton - Genomic Testing in the NHS Deck (216)
Loading flashcards...
1

What pathway do samples take in the NHS from being taken to a report being made?

- assessment of test (input of clinical and/or diagnostic info)
- extraction of DNA/RNA/chromosome preps (or all)
- then either direct mutation analysis, genetic mutation detection or linkage analysis
- get results
- report written (so useful to patient)

2

What does the clinical pathway of a sample start and end with?

- the patient

3

When would direct mutation analysis be carried out on a sample undergoing genomic testing?

- if know what mutation is, eg. if in family already

4

WHen would genetic mutation detection be carried out on a sample undergoing genomic testing?

- if query a certain condition but don't know specific mutation
- eg. if query CF then check CFTR gene
- have to have some understanding of clinical presentation to choose right test

5

What is also important to consider when deciding what tests to do on a sample?

- what patient has consented to

6

What is the referral reason important for?

- to decide what to do w/ sample
- eg. may be query CF, or may be more general

7

What types of sample can be taken prenatally?

- pre-implantation genetic diagnosis (PGD)
- free fetal DNA
- chronic villus sampling
- amniocentesis
- placental biopsy
- fetal blood sampling

8

What types of samples can be taken postnatally (and through to adulthood)

- cord blood
- dried blood spot
- salivary brush
- bone marrow
- cell free (tumour) DNA
- skin biopsy
- venipuncture
- post mortem

9

What is PGD and what can it be used for currently?

- take 1 cell from 8
- currently can only test specific region so have to know what looking for

10

What is the future for PGD?

- will be able to test whole genome eventually
- but should we?

11

What is free fetal DNA, and how is it sampled?

- DNA that circulates freely in maternal DNA
- sampled by venipuncture

12

When is chronic villus sampling taken, and what can happen if its done too early?

- 11 weeks
- clubbing

13

What does an amniocentesis sample?

- sampling amniotic fluid surrounding fetus

14

When can placental biopsies be taken?

- any time after 15 weeks

15

When do RBCs contain DNA?

- is fetuses and newborns up to 6 months

16

What sample is taken from all newborns in England?

- dried blood spot

17

What is the issue w/ amniocentesis?

- risk of miscarriage, but v low risk
- having termination at this time is induced labour

18

How are genes labelled, ie. nts, exons, etc.?

*DIAG*

19

Do cDNA and gDNA contain introns?

- gDNA does
- cDNA is cop of RNA so does not

20

What kind of brackets are used in mutation nomenclature to indicate predicted protein change?

- ( )

21

In mutation nomenclature how would a point change be written for cDNA, eg. C changed to T at position 145?

- c. 145 C>T

22

In mutation nomenclature how would predicted protein be written, for eg. Arg to stop at position 49, or to Leu?

- p. (Arg49*)
- p. (Arg49Leu)

23

What is a nonsense mutation, and how likely is this to be pathogenic?

- AA to stop
- more likely to be pathogenic (but not always), as disrupt prod of protein though nonsense mediated decay

24

What is a missense mutation, and how likely is this to be pathogenic?

- changes AA
- much harder to predict, could be pathogenic or not

25

In mutation nomenclature how would a change in the intron be written for cDNA, eg. for G changed to T at position in intron before 51 in the exon?

- don't want to inc gDNA numbering as well, so use last no, from cDNA, ie -1 means go back 1 towards 5' end (can do from either end)
- eg. c. 51-1G>T

26

In mutation nomenclature how would you write an unknown predicted protein change, and why would we not know?

- p. (?)
- if splice site mutation don't know what it does, as how cell deals w/ it can vary --> exon may be removed or intron inc

27

In mutation nomenclature how would a deletion be written for cDNA, eg. a TG deletion at position 104 to 105?

- c. 104_105delTG

28

What is the effect of a 2 base deletion in mammals?

- disrupts ORF as not multiple of 3
- generally get stop w/in 100 AAs, but usually w/in 10 and often immediately

29

In mutation nomenclature how would the predicted protein change be written for a 2 base deletion, if eg. Cys changed to Tyr at position 34, and frameshift of 12 AAs?

- p. (Cys34Tyrfs*12)
- frameshift is at 12AAs from and inc 1st AA changed --> get stop

30

Do frameshift mutations always mean all AAs afterwards are changed?

- no, sometimes can get some AAs after where maintained