Exam 2 - Genetic testing and Gene therapy

Question 1

Goal of screening

Answer 1

Early identification of a disorder so that intervention can prevent or reverse the disease process

Assist in reproductive decisions

Question 2

Determines the genotypes in individuals that:

Answer 2

1) Already have a disease or predisposed to a disease
e. g. newborn screening
2) Are presymptomatic for a disease
e. g. Huntington disease, breast cancer, colon cancer

3) May have a disease genes that could be passed down to descendants
e. g. Fragile X gene in carrier females

Question 3

Parameters for genetic screening tests:

Answer 3

Validity
Specificity
Sensitivity

Question 4

Validity

Answer 4

Refers to the ability of a test to separate individuals who have the disease from those who do not.

Validity involves 2 components: sensitivity and specificity

Question 5

Sensitivity

Answer 5

the ability to correctly identify those with the disease . It is measured as the proportion of affected individuals who test positive (i.e. true positives)

Question 6

Specificity

Answer 6

ability to correctly identify those without the disease. It is measured as the proportion of unaffected individuals in whom the test is negative (i.e. true negatives)

Question 7

_____ and _____ are determined by comparing the screening results with those of a _____ diagnostic test

Answer 7

Sensitivity
specificity
definitive

Question 8

Test result vs true status

Answer 8

(true status)
+ -
(test) + A B

        -    C     D

Question 9

Sensitivity (calc)

Answer 9

a/a+c

Probability that test is positive when person actually has the disease

Question 10

Specificity (calc)

Answer 10

d/b+d

Probability that test is negative when person truly does NOT has the disease

Question 11

False Positive

Answer 11

b/b+d

Test reports positive for person who does NOT have the disease

Question 12

False Negative

Answer 12

c/a+c

Test reports negative for person who actually has the disease

Question 13

High ____ value results in high ____

Answer 13

“a”

sensitivity

Question 14

High ____ value results in high ____

Answer 14

“d”

specificity

Question 15

PPV

Answer 15

Positive Predictive value

Question 16

Positive Predictive value

Answer 16

• Proportion of positive test results that are truly positive
• answers the question: if my test is positive, what is the chance that I am truly positive for the condition?
• a/a+b

Question 17

NPV

Answer 17

Negative Predictive value

Question 18

Negative Predictive value

Answer 18

Proportion of negative test results that are truly negative

Answers the question: if my test is negative, what is the chance that I am truly unaffected??

d/c+d

Question 19

____ of a test varies based on _____ of the condition in a given pop

Answer 19

PPV

prevalence

Question 20

The ____ the condition in a given pop, lower the ____

Answer 20

rarer

PPV

Question 21

More detailed PPV calculation

Answer 21

Sensitivity x prevalence
(divided by)
(sensitivity x prevalence) + (1-specificy) (1-prevalence)

Question 22

In trying to cast a wider net to catch more patients, the trade off is having __________

Answer 22

increased false-positive rate

Question 23

Screening tests are never 100% ____ and 100% ____.

Answer 23

sensitive

specific

Question 24

non- invasive pre-natal screening methods:

Answer 24

Ultrasound 
Nuchal Translucency Index
Maternal Serum screening 
Triple screen; quad screen 
Fetal cells 
Cell free fetal DNA

Question 25

Invasive pre-natal diagnostic methods:

Answer 25

Amniocentesis Chorionic Villus Sampling (CVS) Percutaneous Umbilical Blood Sampling

Question 26

Ultrasound

Answer 26

Can be used to determine presence of spina bifida (meningomyelocele) displayed as a fluid filled sac in the spinal column

Question 27

Nuchal Translucency Index

Answer 27

Uses ultrasound to measure the translucent space in the tissue at the back of your developing baby's neck.

Question 28

Nuchal Translucency Index used to determine:

Answer 28

baby's risk for Down syndrome (DS) and other chromosomal abnormalities, as well as major congenital heart problems.

Question 29

Babies with abnormalities tend to accumulate more:

Answer 29

fluid at the back of their neck during the first trimester. Result is an enlargement in this region

Question 30

US vs Sonogram

Answer 30

US - the machine that allows you to see your baby during your pregnancy Sonogram - the picture taken of your baby during the ultrasound.

Question 31

______ take _____ images, or 3D sonograms, and adds the element of time to the process.

Answer 31

4D Ultrasounds | 3D Ultrasound

Question 32

In prenatal screening, confirmation of a _____ result should be followed up with _____

Answer 32

positive | diagnostic testing

Question 33

Amniocentesis

Answer 33

20-30 mL of amniotic fluid is withdrawn transabdominally with US guidance

Question 34

Amniocentesis usually occurs:

Answer 34

15-17 weeks gestation

Question 35

CVS procedure:

Answer 35

a catheter is inserted through the cervix and several mg of villus tissue is suctioned with US guidance

Question 36

Fetal treatment is _____

Answer 36

rare

Question 37

Fetal treatment used in the following 3 conditions:

Answer 37

Congenital Adrenal Hyperplasia Biotin-responsive Multiple Carboxylase Deficiency fetal surgery for a neural tube disorder

Question 38

In NBS, _____ screen results need to be followed up with further _______ that is specific for _________

Answer 38

Positive confirmation testing each condition identified

Question 39

Methods of DNA analysis of biosamples:

Answer 39

PCR ASO (allele specific oligonucleotide) using dot blot DNA sequencing Many other methods

Question 40

allele specific oligonucleotide used frequently for:

Answer 40

Sickle cell and cystic fibrosis

Question 41

_________ Is the UltimateWay to Characterize a Clone

Answer 41

DNA Sequencing

Question 42

DNA that you saturate the filter paper with (ASO method)

Answer 42

Probe

Question 43

Antisense strand

Answer 43

Sample DNA from patient that complements either prode

Question 44

Based off how the hybridization occurs in ASO:

Answer 44

You can tell whether patient is homozygous normal, a carrier, or diseased

Question 45

Newer methods of sequencing associated with Next Generation Sequencing (NGS):

Answer 45

Pyrophosphate sequencing

Question 46

DNA sequencing by the _______ developed by _____

Answer 46

chain termination method | Sanger

Question 47

Pyrophosphate sequencing relies on the "___________" principle rather than chain termination

Answer 47

sequencing by synthesis

Question 48

Pyrophosphate sequencing step 1:

Answer 48

ss DNA template is immobilized, and solutions of A, C, G, and T nucleotides are added sequentially to allow for synthesis of complementary strand. Unattached nucleotides are washed off

Question 49

Pyrophosphate sequencing step 2:

Answer 49

Light is emitted when the nucleotide attaches to template. The sequence of light signals allows determination of DNA template sequence.

Question 50

ATPs role in Pyrophosphate sequencing

Answer 50

ATP acts as fuel for luciferase-mediated conversion of luciferin to oxyluciferin that generates visible light in amounts that are proportional to the amount of ATP.

Question 51

How is light captured in Pyrophosphate sequencing

Answer 51

Light produced in the luciferase-catalyzed reaction is detected by a camera/scanner