Gene - Function - Clinic Flashcards
What % of cancers are the BRCA1 and BRCA2 genes responsible for?
. 16% of familial cancers
this accounts for 5-10% of all breast cancers
How does possessing a BRCA gene increase risk of breast cancer?
average woman has 12% risk of developing breast cancer by 90
BRCA1 or BRCA2 increase the risk of breast cancer to 85% by 70
How do the BRCA1 and BRCA2 genes affect risk of ovarian cancer?
normal risk is < 2%
With BRCA1, risk is elevated to 55%
With BRCA2, risk is elevated to 25%
What are the 4 main advantages to testing for BRCA mutations?
- women may feel relieved knowing whether or not they are at a higher risk for breast cancer
- women with breast cancer may have better responses to treatments specifically designed for BRCA positive patients
- women may take preventative measures to reduce their risk of breast cancer (e.g. diet, tamoxifen)
- other family members may want to be tested based on the results
What are 2 treatments for breast cancer specifically designed for BRCA positive patients?
cisplatin and PARP
What are the 4 main disadvantages to testing for BRCA mutations?
- women may become worried, panicked or stressed if they discover they have a higher than average risk
- women who test positive may have difficulty telling family members, who may also have the mutation
- women who test negative may falsely believe they will never get breast cancer
- women who test positive may have to deal with comlications with health or life insurance
What are the options for prophylactic surgery in women who test positive for BRCA mutations?
removing the ovaries after having a family reduces risk by 85%
having a preventative mastectomy reduces risk by 90%
What is the problem with screening for some late onset disorders?
they can be predicted but not prevented
e.g. Huntingdon disease, retinitis pigementosa (late onset blindness)
What is the role of diagnostics and counselling in clinical practice?
- can confirm clinical diagnosis
- can identify carriers of recessive mutations
- can identify cases of non-penetrance
What is meant by non-penetrance/reduced penetrance?
Non-penetrance means that someone carries the gene but do not develop the phenotype
What is Treacher Collins syndrome?
an autosomal dominant disorder with variable penetrance
it is characterised by deformities of the ears, eyes, cheekbones and chin
What complications are most common in Treacher Collins syndrome?
- breathing problems
- problems with sight
- cleft palate
- hearing loss
What is significant about the genetics of the family members of someone with Treacher Collins syndrome?
quite often the parents and grandparents may carry the same mutation as the affected child, but not express the phenotype
What are the main 2 invasive methods of prenatal diagnosis?
Amniocentesis at 17 weeks
Chorionic villus sampling at 11 weeks
What is NIPD? How does it work and what is it used for?
Non invasive prenatal diagnosis - conducted at 10 weeks
It screens the mother’s blood to identify the foetal DNA
It is used for sex determination testing and testing for triploidy and single gene disorders
Why is NIPD termed “cell-free DNA screening”?
Maternal serum contains placental DNA which matches the foetus genome
NGS genome sequencing is performed in the cell-free DNA and the results can identify trisomies
Why is NIPD more likely to be used in the future?
The results are far more accurate than in amniocentesis and have a lower false positive rate
It is also non-invasive, so women are more likely to take it
What is the main drawback of prenatal screening?
Women are having prenatal tests early on in their pregnancy and choosing to terminate them e.g. Down’s syndrome
This means that in Iceland, there are very few Down’s syndrome children
What is meant by preimplantation diagnosis?
It is a form of in utero fertilisation where the embryos are tested first to see if they are positive for a certain known mutation
Only the unaffected embryos are implanted in the uterus
What are the 2 main benefits of preimplantation diagnosis?
- HLA typing can be conducted to match cord blood stem cells for siblings
- Non-disclosure testing can be performed for conditions such as Huntingdon’s disease
What is meant by non-disclosure testing?
Testing that is done without the knowledge of the disease status of the parent
How does non-disclosure testing work?
Instead of screening for the actual mutation, you look for genetic markers either side of the mutation
These are highly polymorphic microsatellite repeats
In this example, how would non-disclosure testing be performed?
- affected grandma has an a allele and a c allele flanking their HD gene - one of these must be affected
- mother has a c allele and a d allele flanking their HD disease
- we do not know whether it is an a or a c allele that carries the HD mutation
- we only implant the embryos that have inherited the d allele from the mother as these have come from the grandad who does not have HD
What is gene therapy? How is classic gene therapy conducted?
It is the use of genetic material - DNA or RNA - as a medicine
Classic gene therapy involves the introduction of functional genes, in the form of DNA, to replace mutated genes
