Genetics Flashcards
Define multifactorial inheritance
The presence of multiple small genetic and environmental risk factors.
Three classes of gene involved in tumorigenesis
Proto-oncogenes
Tumor suppressor genes
DNA repair genes
Single gene disorders
A mutation in a single gene is sufficient to cause disease
Non-penetrance
Affected genotype but no change in phenotype
Recurrence risk increases with..
Frequency in population
Number of affected relatives
Age of onset in relatives
Predisposing environmental factors
What is Knudson’s 2-hit hypothesis
Loss of tumour suppression requires LOF of both alleles of a relevant gene
Mode of inheritance for TS gene
AD
Inhibition of TS gene may be caused by..
LOF mutation Epigenetic silencing (methylation of promotor)
Example of DNA repair gene
BRCA1/2
What factors should lead you to suspect hereditary breast cancer
Pedigree suggests AD Early onset breast cancer Multi focal/bilateral breast cancer Male breast cancer Ovarian cancer
Why does BRCA fit into 2-hit hypothesis
20% of people with mutation don't get cancer Variable expressivity (age, location, males less)
Groups that have common BRCA mutations
Afrikaners
Ashkenazi Jews
Icelanders
[Founder effect]
Process of genetic counseling and genetic testing
- Identify most at risk = cost effective.
- Start genetic test in affected person (more confident gene causes disease)
- Offer fam member the genetic test
