Applied Genetics in Medicine

Question 1

What is the first step in diagnosis for population screening?

Answer 1

Confirmatory testing

Question 2

What is the goal behind population screening?

Answer 2

Allow intervention of affected individuals and/or more informed reproductive decisions in carriers

Question 3

Which of the following newborn screening test is not required in all 50 states?

• Phenylketonuria
• Galactosemia
• Hypothyroidism
• Hemoglobinopathies

Answer 3

*Hemoglobinopathies

Question 4

What is Phenylketonuria?

Answer 4

Inability to process AA phenylalanine

Question 5

What can Phenylketonuria cause if not treated early?

Answer 5

Mental impairment

Question 6

Who developed the method to diagnose Phenylketonuria?

Answer 6

Robert Guthrie

Question 7

What causes Cystic Fibrosis?

Answer 7

Abnormal transport of chloride in alveolar epithelium leading to thickened secretions + pulmonary infections

Question 8

What kind of screening is involved for Cystic Fibrosis?

Answer 8

Heterozygote Screening

Question 9

What mutation causes Cystic Fibrosis?

Answer 9

F508; causes loss of phenylalanine

Question 10

Prenatal screening is (invasive/non-invasive)

Answer 10

Both

Question 11

How is non-invasive prenatal screening done?

Answer 11

Detectable at 6 to 8 weeks using cell-free DNA from fetal tissue

Question 12

Is non-invasive prenatal screening a confirmation of a particular diagnosis?

Answer 12

No, still requires amnio or chorionic villus sampling (invasive)

Question 13

BRCA1 and BRCA2 mutations are more prevalent in what ethnicity?

Answer 13

Scandinavians + Askenazi Jewish descent

Question 14

APOE protein transports what?

Answer 14

Lipids, particularly cholesterol

Question 15

Which allele of APOE gene increases risk for cardiovascular disease?

Answer 15

epsilon 4 allele (ε4)

Question 16

Besides cardiovascular diseases, what else does epsilon 4 allele cause?

Answer 16

Alzheimer’s disease risk

Question 17

Risk due to APOE4 (for Alzheimer’s) is higher in which race?

Answer 17

Asians

Question 18

What percentage of Alzheimer’s pts are APOE4 negative?

Answer 18

1/3

Question 19

What percentage of drugs are associated w/ severe adverse drug reactions (SADRs)?

Answer 19

15%

Question 20

How can you treat for long QT syndrome?

Answer 20

Block Calcium & Sodium

Question 21

Why is it hard to treat hypertension via ACE inhibitors or Beta-blockers?

Answer 21

None of the variants are commonly tested

ACE inhibitors - if pt is homozygote (recessive), they are responsive to inhibitors due to having reduced activity because of deletion

Question 22

What is an example of a variant w/ BROAD effects?

Answer 22

CYP2D6; affects metabolism of more than 25% of pharmaceuticals

Question 23

Rather than race, which is a better predictor of ancestry?

Answer 23

Genetic information

Question 24

What is sensitivity?

Answer 24

Ability to detect true positives

Question 25

What is specificity?

Answer 25

Ability to detect true negatives

Question 26

What are the polymorphisms that are helpful in determining risk for complex diseases?

Answer 26

There are none lol

Question 27

What acts as a surrogate for genetic information?

Answer 27

Family history

Question 28

Genetic tests are used nearly exclusively for what?

Answer 28

1. Mendelian traits (like birth defects)
2. Metabolic disorders
3. Cancer

Question 29

For complex diseases, very few polymorphisms provide info not available thru family history due to what?

Answer 29

Genetic etiology of complex diseases

Question 30

Rare alleles have (large/small) effect sizes with (high/low) penetrance

Answer 30

large size + high penetrance

Question 31

Common genes have (large/small) effect sizes with (high/low) penetrance

Answer 31

small size + low penetrance