Predictive Genetic Tesing Flashcards
Types of genetic testing?
Diagnostic genetic testing
Predictive genetic diagnosis
Prenatal (and preimplantation) genetic diagnosis
Carrier testing
Autosomal recessive
Sex-linked or chromosomal rearrangement
Susceptibility testing
Identity Testing
Ancestry testing
Predictive testing?
CK - Duchenne and Beckers
Coag factos for haem
Renal USS for polycystic kidney disease
Colonoscopy for familial adenomatour polyposis coli
Sweat electrolytes for cystic fibrosis
Enzyme assays or biochemistry for inborn erros on urine blood or cells.
Testing in children?
Should be predictive:
A medication needs to be present
or if parents are anxious
otherwise you need to defer until adult of competent.
Triplet repeat disease?
HD, SCA(s), myotonic dystrophy, Kennedy’s
Common mutations? (Founder effects)
Ashkenazi BRCA1/2 mutations; FH in Quebec
HD repeat severity?
<27 repeats - normal
27-35 repeats – intermediate (unstable)
36-39 repeats – reduced penetrance
40+ repeats – full penetrance
~60 up to ~100 – juvenile onset
Homozygous <27 - ? failure to detect an expansion
Counselling for BRCA1/2?
Decisions about prophylactic surgery
mastectomy, öophorectomy
Medical approaches to risk reduction
eg tamoxifen
Improved access to surveillance for tumours
Dangers of increased surveillance ??
prediciton
Prediction = Mendelian
– the predominant risk factor within that family
• Susceptibility = risk assessment for a complex
disease (i.e. multifactorial disease)
– relative risks over given period of time
– compared to background risk in that population
– early life experiences may be important, as in
Predictive Adaptive Responses – the Barker effect
risk assessment
Genome-Wide Association Studies
– Single nucleotide polymorphisms = SNPs
– Ancient and therefore weak associations
– Account for only modest proportion of heritability
• Interpretation of Whole Genome Sequence
– plus methylation, chromatin conformation, …
– may prove to be much more helpful
