gene function

Question 1

what comprises hypothesis generating?

Answer 1

without any prior knowledge we can identify which genes, proteins and pathways are involved in development and disease whether they are monnogenic or complex. Identification of genes allows for accurate diagnosis, counselling and determination of function and also identifies a target for therapy

Question 2

how is genetics used?

Answer 2

for diagnosis, counselling, therapy treatment and prevention

Question 3

what diagnosis can there be for neonates?

Answer 3

presymptomatic, preimplantation or prenatal

Question 4

what genes may involve counselling?

Answer 4

BRCA1/2 for ovarian and brast cancer development

Question 5

what is BRCA mutations responsible for?

Answer 5

responsible for 16% of familial cancers and 5-10% of all breast cancers

Question 6

what is the increase of risk for breast and ovarian cancer with BRCA1/2 gene?

Answer 6

usual breast risk is 12% by 90y/o
with BRCA mutations increases risk to 85% by 70y/o
usual ovarian risk is <2%
with BRCA1 is 55% and BRCA2 25%

Question 7

what are the benefits of being tested for BRCA?

Answer 7

mind at rest
risk reducing activities such as diet and tamoxifen
treatment plans
other family members

Question 8

why does testing direct treatment plan?

Answer 8

BRCA mutations in cancer respond to other treatments better than usual treatments - cisplatin and PARP inhibitors

Question 9

what are the disadvantages of testing for BRCA?

Answer 9

anxiety
guilt
false reassurance of never getting breast cancer
complications e.g. insurance

Question 10

what are the prophylactic options for BRCA?

Answer 10

removal of ovaries after having a family - reduces risk by 85%
preventative masectomy - reduces risk by 90%
these are popular due to advances in reconstructive surgery

Question 11

what can you presymptomatically test for?

Answer 11

late onset disorders - breast and colon cancer, HDD and retinitits pigmentosa

Question 12

why would diagnostics help counselling?

Answer 12

confirm the clinical diagnosis, identify carriers of recessive mutations and identify cases of non-penetrance

Question 13

what is TCS?

Answer 13

it is a congenital abnormality where there is deformity of ears, eyes, cheekbones and chin and can range from mild to severe

Question 14

how would TCS be tested for?

Answer 14

prenatal diagnosis
amniocentesis - 17 weeks
CVS - 11 weeks
NIPD - 10 weeks

Question 15

what else can be tested for in prenatal diagnosis ?

Answer 15

triploidy and single gene disorders

Question 16

what is NIPD?

Answer 16

non invasive prenatal diagnosis - it is a new non invasive method that is based on NGS of the mothers blood at ten weeks - cell free DNA screening

Question 17

what is the process of NIPD?

Answer 17

the maternal serum contains placental DNA that matches the foetal genome. NGS genome sequencing is performed on the cell free DMA and the results will identify trisomies

Question 18

what are the advantages of NIPD?

Answer 18

much more accurate (<99% compared to current 85% for Downs) and much lower false positive rate (0.06% compared to current 5.4% for Downs)

Question 19

what is pre-implantation diagnosis?

Answer 19

it is when there is HLA typing to match the cord blood stem cells for siblings for a saviour sibling

Question 20

who oversee pre-implantation diagnosis?

Answer 20

HFEA - human fertilisation and embryology authority

Question 21

when can pre-implantation non disclosure testing be performed?

Answer 21

for HDD - without knowledge of the disease status of the parent

Question 22

what is gene therapy?

Answer 22

it is the use of genetic material such as DNA or RNA as a medicine q

Question 23

what is classic gene therapy?

Answer 23

it is the introduction of functional genes in the form of DNA to replace mutated genes

Question 24

what is novel gene therapy?

Answer 24

it is using gene technology to repair mutated genes, silence overactive genes or provide immune cells with the tools that they need to recognise and kill cancer cells and infections

Question 25

what is Leber’s congenital amaurosis?

Answer 25

LCA is a rare inherited eye disorder that has over 22 genes implicated and is a recessive inheritance pattern. It account for 10-18% of congenital blindness, and results in blindness at birth or in infancy, or impaired visual function resulting in inability to see wise with only a small circle of vision. It is a target of gene therapy

Question 26

why is the eye a target for gene therapy?

Answer 26

it is immune privileged and is accessible for subretinal injections

Question 27

what is an example of gene therapy in LCA?

Answer 27

RPE65 mutations have been identified in LCA families which is a retinal enzyme. A sub-retinal injections between RPE and photoreceptors that is made of adeno associated virus containing RPE65 and RPE65 promoter may restore vision - unsure of benefits as of yet

Question 28

what is DNA editing?

Answer 28

CRISPR/Cas9 is a find and replace process. A cell is transfected with an enzyme complex containing a guide molecule to find the target DNA strand, healthy DNA copy and a DNA cutting enzyme. The enzyme cuts off the defective DNA strand and it is replace with a healthy copy

Question 29

what does pharmacogenetics show?

Answer 29

there is a correlation between the effect of drugs and the genetic constitution of patients

Question 30

what is the prevalence of adverse drug reactions?

Answer 30

5-7% of hospital admissions are due to adverse drug reactions

Question 31

what is the cytochrome P450 oxidases?

Answer 31

they are a multigene family of enzymes that are found predominantly in the liver and are responsible for the metabolic elimination of most drugs used and the conversion of pro-drugs into their active forms

Question 32

what is codeine converted into?

Answer 32

the analgesic morphine

Question 33

what is CYP2D6?

Answer 33

it is a highly polymorphic cytochrome 450 member that converts codeine to morphine. The desired analgesic effect is not achieved in CYP2D6 poor metabolisers - where there is no active CYP2D6.

Question 34

what is the role of CYP2D6 other than for codeine?

Answer 34

it metabolises 25% of drugs

Question 35

what is the prevalence of CYP2D6 mutations?

Answer 35

6-10% of caucasians are non-metabolisers

7% of caucasians are ultra rapid metabolisers - multiple copies of CYP2D6

Question 36

is there genetic testing for CYP2D6 poor metabolisers?

Answer 36

privately yes

Question 37

why are some people poor CYP2D6 metabolisers?

Answer 37

due to polymorphisms in CYP2D6

Question 38

what is poor metabolism of CYP2D6 associated with?

Answer 38

poor survival with tamoxifen

Question 39

what is the active metabolite of tamoxifen and how is it coverted?

Answer 39

endoxifen is the active metabolite

CYP2D6 is the rate limiting step that converts tamoxifen to endoxifen

Question 40

GPs have access to genotyping tests. How does this affect the treatment of conditions?

Answer 40

there is information about a person genotype or gene expressionn profile. This is used to tailor medical care. They can prescribe depending on the results and change lifestyles to fit results

Question 41

what are direct to consumer tests?

Answer 41

they are £125 tests for over 240 diseases that patients receive the results for at home and are advised to see HCP

Question 42

what are three examples of direct to consumer tests?

Answer 42

parkinsons
BRCA
delta F508 mutation in CF