Types of genetic tests (hint: screening to diagnose and predict prognosis)
"screening to diagnose and predict prognosis"
Diagnostic test (e.g. CF)
Predictive test (e.g. BRCA/cancer)
Prognostic test (cancers)
Test characteristics (2 categories)
Accuracy of disease prediction/how well test predicts disease
Usefulness of test results treatment/patient management
Effect of test results on patient (patient's life basically)
Categories of etiologies
Copy number changes
Point mutation types
Missense (conservative vs nonconservative)
Conservative vs Nonconservative missense mutations
Conservative - results in AA change; new AA resembles WT AA in function (so no functional difference)
Non-conservative - results in AA change; new AA functionally different from WT AA (gain or loss of function)
Types of Copy number changes
Microdeletion/duplication (e.g. CF = loss of 1 bp)
Repeat expansion types and locations
Trinucleotide expansion (CGG) or Dinucleotide
Located within gene, promoter or intron
Methylation of CpG islands
Molecular diagnostic techniques
"RFLP e sequence"
"Microsatellites methylate ASO's"
Methylation testing (via Southern)
RFLPing the sequence!!
Microsatellites methyl8 ASO's!!
Point mutation genetic test used
RFLP (SNP type)
Test for repeat expansions
Test for methylation
Test for copy number changes
Multiplex ligation-dependent probe amplification
Multiplex ligation dependent amplification
Essentially, PCR with 2 primers >>
each w/ probe on one end>>
If mutated sequence = amplification but wrong size
If no mutation = amplification + right size
Next generation sequencing types
Targeted gene panels
Exome sequencing (highest coverage) [coding regions only]
(Whole) Genome sequencing
3 false negative scenarios
Down Syndrome etiologies
Tests for DS
Test to order for DS
Fragile X Syndrome etiology
Tests for Fragile X Syndrome
Which test would you order for Fragile X?
Trinucleotide repeat analysis
Intepret the Southern Blot below of Fragile X patients. Give reasons for each intepretation.
Prader Willi Syndrome etiologies
Why would you choose methylation testing for PWS and not any of the other tests?
MLPA and FISH will only detect gain/loss of genetic info
Microarray won't detect UPD
UPD analysis won't detect deletion