Genetics Intro

Question 1

What are the 2 general uses for genetic testing?

- are these methods directive or non-directive?

Answer 1

1. Medical Management
   - Directive
2. Personal Decision Making
   - Non-directive

Question 2

What are the reasons to get a genetic test for Medical Management?

Answer 2

• Diagnosis
• Treatment
• Predictive with a TREATMENT

Question 3

What are the reasons to get a genetic test for personal decision making?

Answer 3

• Predictive WITHOUT a treatment
• Carrier Testing/screening
• Prenatal Diagnosis

Question 4

Someone gets a test to see if they are a carrier of Huntington’s, does this fall under the category of Medical Management or Personal Decision making?

Answer 4

• Personal Decision Making because there is no treatment for the disease

Question 5

You want to see if a patient has CF what kind of test would you start out with?

Answer 5

• Targeted: 75% of CF cases involve a mutation at a single point so you are likely to catch the disease by this test if its there

Question 6

What are two ways to scan a gene?

Answer 6

• Sequence

- Gene Array

Question 7

What is population stratification?

Answer 7

• Varying Allele Frequencies across populations

Question 8

CFTR

• Mode of Inheritance
• % point mutations
• % large deletions/duplications

Answer 8

• Autosomal Recessive
• 90% = point mutations
• 10% = large deletions/duplications

Question 9

BRCA1

• Mode of Inheritance
• % point mutations
• % large deletions/duplications

Answer 9

• Autosomal Dominant
• 85% = point mutations
• 15% = large deletions/duplications

Question 10

T or F: CFTR and BRCA1 have a high de novo mutation rate

Answer 10

False, they have a low de novo mutation rate so most cases its an inherited condition

Question 11

What disease that we’ve studied has a high mutation rate?

Answer 11

• DMD, lot of allelic Heterogeneity

Question 12

What is the mode of inheritance for DMD?

Answer 12

• X-linked Recessive

Question 13

What is the mode of inheritance for Huntington’s?

Answer 13

• Autosomal Dominant

Question 14

T or F: gene panels can be targeted for specific mutations

Answer 14

False, but MUTATION panels are considered targeted because you’re just looking for one mutation here or there that causes the disease

Question 15

What are the strengths and limitations of targeted testing?

Answer 15

Strengths:
1. HIGH accuracy for the SPECIFIC alleles being tested

2. Widely available at low cost

Limitations:
1. No Information about other potentially significant variants

Question 16

When is Gene Scanning the appropriate method for detecting the cause of a disease?

Answer 16

• If there is lots of allelic heterogeneity aka “private mutations”

Question 17

T or F: with gene scanning you are likely to uncover many deviations from the normal gene sequence

Answer 17

True - you will likely uncover many SNPs that are benign

Question 18

With Scanning tests you are likely to still miss a lot of information. What info. are you likely to miss with these types of tests?

Answer 18

• Repetitive Sequences

- Introns usually are not sequenced

Question 19

With a Scanning Test what does it mean to have:

• Positive Result
• Negative Result

Answer 19

Positive:
- Pathogenic Variant identified

Negative:

• Test Failed to Provide Useful information
• Risk of False Negative

Question 20

T or F: Benign Variants are always expected in scanning tests

Answer 20

True, also VUSs often accompany but they cannot be used to make any clinical decisions

Question 21

What are the strengths and limitations to gene scanning?

Answer 21

Strengths:

• Comprehensive
• Good Sensitivity
• Can identify so cheaper targeted testing can be used in the future

Limitations:

• Not all Mutations Will be Detected
• Negative Results do NOT rule out hereditary risk
• Results may be hard to interpret

Question 22

Why do negative results not rule out hereditary risk in gene scanning?

Answer 22

• It could be the case that there’s a strong family history of the disease but the scan simply misses the pathogenic part

Question 23

What are the only 2 types of results that can be obtained from a targeted approach?

Answer 23

1. Has the mutation

2. Does not have mutation

Question 24

What type of test would you use for:

• HBOC
• CFTR

Answer 24

HBOC - Sequencing

CFTR - Targeted

Question 25

What does clinical utility of a genetic test refer to?

Answer 25

The ability of a test to improve outcome

Question 26

T or F: regardless of gene and general approaches a sequencing test should be used to look for KNOWN FAMILIAL mutations.

Answer 26

False, it a certain mutation occurs within the family then TARGETED approach should be used