Genomic Applications

Question 1

What 3 conditions are targeted at Tier 1 genomic applications based on evidence supporting potential for Positive impact on public health?

Answer 1

1. Hereditiary Breast and Ovarian Cancer (HBOC)
2. Lynch Syndrome
3. Familial Hypercholesterolemia

Question 2

What is Lynch Syndrome?

- what gene does the mutation affect

Answer 2

Hereditary Cancer Syndrome, including COLORECTAL and other tumors
- affects mismatch repair genes

Question 3

Familial Hypercholesterolemia (FH)

• Phenotype
• Prevalence
• Inheritance
• number diagnosed

Answer 3

Phenotype:
- Abnormally High Serum LDL

Prevalence:
- 1 in 500

Inheritance:
- Autosomal Dominant

Number Diagnosed:

Question 4

What might you see in the eyelids of a patient with extremely high cholesterol?

Answer 4

xamphomas

Question 5

What screening is used for FH?

Answer 5

Cascade Screening

Question 6

Cascade Screening

- how is it conducted?

Answer 6

1. You diagnose someone with a disease (e.g. FH)
2. Screen 1st degree relatives for the disease (high cholesterol)
3. Screen systematically for 2nd and 3rd degree relatives

**Most of the time genetic testing is only done in the index case

Question 7

Why is Cascade Screening Beneficial?

Answer 7

• It allows for early intervention (put patients on Statins etc.)

Question 8

Compare Traditional Sequencing to Next Generation Sequencing.

• Methods
• Sequences per Reaction Vessel

Answer 8

Traditional:

• Sanger Sequencing
• One Reaction Vessel
• One Sequence

Next-Gen:

• Many different methods
• One Reaction Vessel
• Tons of Genomic Sequence Produced

Question 9

What are the Pros and Cons of doing a genomic Sequence?

Answer 9

Pros:
- Identifies Clinically Significant Pathogenic Variants

Cons:
- Even people who are seemingly normal may be found to have pathogenic variants

Question 10

What are the different methods of Clinical Sequencing?

Answer 10

1. Single Gene
2. Gene Panel
3. Exome
4. Whole Genome
5. Cancer Genome
6. Family Genome

Question 11

What does is mean to target a single gene in clinical sequencing?
- when would you do this?

Answer 11

• You Sequence only one gene
• Do this when Diagnosis is already pretty definitive and you just need conformation

**E.g. DMD, Cystic Fibrosis

Question 12

What does it mean to run a gene panel?

- When would you do this?

Answer 12

• You sequence a panel of genes related to a particular disorder that you suspect is causing disease

Question 13

What does it mean to sequence the exome?

-when would you do this?

Answer 13

• Sequence all of the Coding DNA (~1% of genome)

- Would Use if Unsure what the disease was

Question 14

What would you do if you clincally sequenced clinically sequenced a cancer genome?

Answer 14

• Compare tumor sequence to the normal somatic Sequence

Question 15

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.

Answer 15

True

Question 16

In ANY clinical sequencing case what must you do with the results?

Answer 16

• Compare to Reference Sequence

- Differences analyzed to see if they will be pathogenic

Question 17

What does expression profiling look at?

• Why is this beneficial?
• What does it NOT look at?

Answer 17

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

Question 18

How does expression profiling lead to more targeted treatment of diseases?

Answer 18

• 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

Question 19

What are companion Diagnoistics used to determine?

Answer 19

• 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

Question 20

T or F: Vemurafenib can only be used in the presence of a BRAF V600E Mutation

Answer 20

True, presence of BRAF V600E is necessary for the drug to be effective

Question 21

What is Direct to Consumer (DTC) Testing?

Answer 21

-patient can get genetic testing done outside of the healthcare system

Question 22

What are the main problems with DTC testing?

Answer 22

1. 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
2. Test results may also be misinterpreted