L13- Gene - Function - Clinic

Question 1

Advantages to testing for BRCA mutations

Answer 1

Women with breast cancer may have better responses to certain treatments that are specifically designed for BRCA positive patients (eg. cisplatin and PARP inhibitors).

Women may take preventive measures to help reduce their risk of breast cancer if they test positive for BRCA mutations (diet, exercising, tamoxifen).

Other family members may decide if they wish to be tested for BRCA mutations based on the results of a woman’s test.

Question 2

Disadvantages to testing for BRCA mutations

Answer 2

Women may become worried, panicked, or stressed if they discover they have a higher than average risk for breast cancer.

Women who test positive for BRCA mutations are faced with the difficulty of telling family members (some of whom may also have the mutation).

Women who test negative for BRCA mutations may falsely believe they will never get breast cancer.

Women who test positive for BRCA mutations may have to deal with complications with health or life insurance.

Question 3

Presymptomatic screening can help to predict which diseases

Answer 3

Late onset disorders – Huntington’s disease
Retinitis pigmentosa
Breast Cancer
Colon cancer

Predict but can’t prevent

Question 4

Prenatal diagnosis methods

Answer 4

Amniocentesis (~17 weeks)

Chorionic villus sampling (~11 weeks)

Maternal peripheral blood (sex)

New non-invasive method based on NGS of mothers blood (10 weeks).

Question 5

What is Non-disclosure testing?

Answer 5

Testing for diseases in embryo? Without knowledge of disease status of the parent

e.g Huntingtons

Question 6

Leptin deficiency

Answer 6

is the satiety hormone…and a deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight.

Leptin replacement therapy is the management

Question 7

What is Gene Therapy

Answer 7

Gene therapy is the use of genetic material- DNA or RNA- as a medicine

It can be seen as the introduction of functional genes, in the form of DNA, to replace mutated genes.

repair mutated genes, silence overactive genes and to also provide our immune cells with the tools they need to recognise and kill cancer cells and infections

Question 8

Leber’s congenital amaurosis (LCA)

Answer 8

Rare inherited eye disorder

Blindness at birth or in infancy

Accounts for 10-18% of congenital blindness

RPE65 (important in light transduction) mutations identified in 1997 in LCA families

Recessive inheritance pattern

Can only see the central part of vision

Question 9

Why is gene therapy convenient in the eye?

Answer 9

Eye is immune privileged

Eye is accessible for subretinal injection

Question 10

How is Leber’s congenital amaurosis (LCA) managed?

Answer 10

Gene therapy

Sub-retinal injection between RPE and photoreceptors with adeno-associated virus containing human RPE65 and human RPE65 promotor

Question 11

What are Cytochrome P450 oxidases

Answer 11

Multigene family of enzymes found predominantly in the liver

Responsible for the metabolic elimination of most drugs currently used

Also important for converting pro-drugs to their active forms (eg codeine)

Question 12

CYP2D6, which drug does it metabolise?

Answer 12

Highly polymorphic cytochrome 450 family member

Involved in Tamoxifen metabolism

CYP2D6 rate limiting step converting tamoxifen to its active metabolite endoxifen

Poor metabolizers due to CYP2D6 polymorphisms are associated with worse survival

Question 13

What is Personalized Medicine

Answer 13

Information about a persons genotype or gene expression profile used to tailor medical care