T2: From gene to function to clinic Flashcards
How is genetics used in medicine today?
- Diagnosis: presymptomatic, prenatal and preimplantation
- Counselling
- Treatment
- Therapy
- Prevention
How is the BRCA1 and BRCA2 gene involved in the development of breast cancer?
This family of genes is responsible for 16% of familial cancers. It accounts for 5-10% of all breast cancers.
The average woman has a 12% risk of developing breast cancer. BRC1 or BRCA2 increases the risk to 85%. It also increases the risk of developing ovarian cancer.
What types of prenatal testing is available?
- Amniocentesis (~17 weeks)
- Chorionic villus sampling (~11 weeks)
- NIPD - New non-invasive method based on NGS of mothers blood (10 weeks).
- NHS offer sex determination testing
- Use for triploidy and single gene disorders testing in NHS trials
How does non-invasive prenatal testing/diagnosis work?
Maternal serum contains placental DNA which matches the foetus genome. NGS genome sequencing is performed on the cell-free DNA and the results can identify trisomy’s. It is very accurate.
What is preimplantation testing?
PGD, also known as preimplantation genetic testing (PGT-M), is a treatment which involves checking the genes or chromosomes of your embryos for a specific genetic condition. The embryos without the condition can then be implanted using IVF.
What is non-disclosure testing?
Non-disclosure testing - we can perform screening of the embryos without diagnosing the parent.
What is precision therapy?
A strategy that integrates molecular information with clinical data to select the best therapeutic intervention. We would just give the patient what benefits them.
What is gene therapy?
- Gene therapy is the use of genetic material- DNA or RNA- as a medicine.
- Classic gene therapy - introduction of functional genes, in the form of DNA, to replace mutated genes.
- Using gene technology to 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.
What is CYP2D6?
YP2D6 - Highly polymorphic member of the cytochrome P440 oxidase enzyme family. Metabolises 25% of drugs. However 6-10% of Caucasians are non-metabolisers as they have no active form of the gene. 7% of Caucasians are ultra-rapid metabolisers (they have multiple copies of the genes, leading to multiple copies of the protein and so they metabolise the drug much faster than it can have an effect).
How can gene knowledge be used in the prescription of Tamoxifen?
Tamoxifen metabolism
- CYP2D6 rate limiting step converting tamoxifen to its active metabolite endoxifen.
- Poor metabolizers due to CYP2D6 polymorphisms are associated with worse survival.
Genetic testing now available privately.
What is preventative medicine?
Information about a persons genotype or gene expression profile used to tailor medical care to prevent disease.
What are incidental findings?
Incidental rings are previously undiagnosed medical or psychiatric conditions that are discovered unintentionally and are unrelated to the current medical or psychiatric condition which is being treated or for which tests are bing performed. You can only report back actionable results - this is known as secondary findings.
