Genomic Applications Flashcards
What 3 conditions are targeted at Tier 1 genomic applications based on evidence supporting potential for Positive impact on public health?
- Hereditiary Breast and Ovarian Cancer (HBOC)
- Lynch Syndrome
- Familial Hypercholesterolemia
What is Lynch Syndrome?
- what gene does the mutation affect
Hereditary Cancer Syndrome, including COLORECTAL and other tumors
- affects mismatch repair genes
Familial Hypercholesterolemia (FH)
- Phenotype
- Prevalence
- Inheritance
- number diagnosed
Phenotype:
- Abnormally High Serum LDL
Prevalence:
- 1 in 500
Inheritance:
- Autosomal Dominant
Number Diagnosed:
What might you see in the eyelids of a patient with extremely high cholesterol?
xamphomas
What screening is used for FH?
Cascade Screening
Cascade Screening
- how is it conducted?
- You diagnose someone with a disease (e.g. FH)
- Screen 1st degree relatives for the disease (high cholesterol)
- Screen systematically for 2nd and 3rd degree relatives
**Most of the time genetic testing is only done in the index case
Why is Cascade Screening Beneficial?
- It allows for early intervention (put patients on Statins etc.)
Compare Traditional Sequencing to Next Generation Sequencing.
- Methods
- Sequences per Reaction Vessel
Traditional:
- Sanger Sequencing
- One Reaction Vessel
- One Sequence
Next-Gen:
- Many different methods
- One Reaction Vessel
- Tons of Genomic Sequence Produced
What are the Pros and Cons of doing a genomic Sequence?
Pros:
- Identifies Clinically Significant Pathogenic Variants
Cons:
- Even people who are seemingly normal may be found to have pathogenic variants
What are the different methods of Clinical Sequencing?
- Single Gene
- Gene Panel
- Exome
- Whole Genome
- Cancer Genome
- Family Genome
What does is mean to target a single gene in clinical sequencing?
- when would you do this?
- You Sequence only one gene
- Do this when Diagnosis is already pretty definitive and you just need conformation
**E.g. DMD, Cystic Fibrosis
What does it mean to run a gene panel?
- When would you do this?
- You sequence a panel of genes related to a particular disorder that you suspect is causing disease
What does it mean to sequence the exome?
-when would you do this?
- Sequence all of the Coding DNA (~1% of genome)
- Would Use if Unsure what the disease was
What would you do if you clincally sequenced clinically sequenced a cancer genome?
- Compare tumor sequence to the normal somatic Sequence
T or F: if you do a clinical sequence on a family then any de novo sequences are likely to be the cause of the disease.
True
In ANY clinical sequencing case what must you do with the results?
- Compare to Reference Sequence
- Differences analyzed to see if they will be pathogenic
What does expression profiling look at?
- Why is this beneficial?
- What does it NOT look at?
Looks at levels of RNA expression
- We can look at the sequences (proteins) being overproduced and underproduced
DOES NOT look for genetic mutations
***We just want to know how cell Expression of existing genes has changed
How does expression profiling lead to more targeted treatment of diseases?
- has high PROGNOSTIC value (what is the tumor type etc.)
Example:
- Breast Cancer patient may not need Chemo after surgery if the RNA expression is consistent with a tumor with so metastatic potential
What are companion Diagnoistics used to determine?
- They determine if a patient possesses a target (using targeted sequencing) that makes a certain treatment an option possible
***Treatment options here can ONLY be used if a POSITIVE test result is obtained
T or F: Vemurafenib can only be used in the presence of a BRAF V600E Mutation
True, presence of BRAF V600E is necessary for the drug to be effective
What is Direct to Consumer (DTC) Testing?
-patient can get genetic testing done outside of the healthcare system
What are the main problems with DTC testing?
- May test for Common Polymorphisms that are linked to disease
- issue because this may be only one risk factor among many needed to produce deleterious phenotype - Test results may also be misinterpreted
