Genetic Testing

Question 1

Genetic Testing is defined as…

Answer 1

The analysis of chromosomes, DNA, RNA, proteins, or other analyses to detect abnormalities that can cause genetic disease.

Question 2

Broad indications for genetic testing include:

Answer 2

• Prenatal diagnosis
• heterozygote carrier detection
• Presymptomatic diagnosis of genetic disease

Question 3

______ is large-scale testing of populations for disease in an effort to identify persons who probably have the disease and those who probably do not.

Answer 3

Population screening

Question 4

Is population screening for
genetic variants that can cause the disease in the
person carrying the variant or in the descendants
of the carrier.

Answer 4

Genetic screening

Question 5

The test’s validity involves two components:

Answer 5

sensitivity and specificity

Question 6

Sensitivity reflects…

Answer 6

The ability of the test to
correctly identify those
with the disease

Question 7

Specificity is the ability of
the test to correctly
identify…

Answer 7

those without the
disease.

Question 8

Mendelian disorders

Answer 8

These disorders result from mutations that have high penetrance (proportion of individuals presenting with the disease or phenotype among carriers of the mutation and the mode of
inheritance) and varying expressivity (different clinical/pathologic manifestations from mild to
severe disease).

Question 9

Evaluation of clinical test diagram:

Answer 9

Question 10

_____ screening programs represent an ideal opportunity for pre-symptomatic detection and prevention of genetic disease.

Answer 10

Newborn screening programs

Question 11

Heterozygote screening

Answer 11

can be applied to the detection of unaffected carriers of disease-causing mutations.

Question 12

Genetic diseases amenable to heterozygote screening are typically…

Answer 12

Autosomal recessive disorders for which prenatal diagnosis and genetic counseling are available, feasible, and accurate.

Question 13

An example of Heterozygote screening effort is the…

Answer 13

Tay–Sachs screening program in North America. Common among Ashkenazi Jews.

Question 14

Infantile Tay–Sachs disease is an autosomal recessive
lysosomal storage disorder in which…

Answer 14

the lysosomal enzyme β- hexosaminidase A (HEX A) is deficient, causing a buildup of the substrate, GM2 ganglioside, in neuronal lysosomes.

Question 15

The accumulation of this substrate (GM2 ganglioside) damages the neurons and leads to:

Answer 15

-blindness
-seizures
-hypotonia
-death by about 5 years of years of age.

Question 16

_______ (another serious autosomal recessive disorder) is especially common among many Mediterranean
and South Asian populations.

Answer 16

β-Thalassemia major

Question 17

Presymptomatic Diagnosis has become feasible for many genetic diseases.

Answer 17

At-risk persons can be tested to determine whether they have inherited a disease-causing mutation.

Question 18

Presymptomatic diagnosis is available for:

Answer 18

-Huntington’s disease
-adult polycystic kidney disease
-Autosomal Dominant breast/ovarian cancer

Question 19

Prenatal diagnosis is a major focus of genetic testing; the principal aim of prenatal diagnosis is to…

Answer 19

supply at-risk families with information to make informed choices during pregnancy. The potential
benefits of prenatal testing include:

Question 20

Amniocentesis is typically performed at…

Answer 20

15 to 17 weeks after a pregnant woman’s last menstrual period (LMP)

Question 21

Chorionic Villus Sampling (CVS) is performed by…

Answer 21

Aspiring fetal trophoblastic tissue (chorionic villi) by either a transcervical or transabdominal approach. Because it is usually performed at 10 to 11 weeks post-LMP, CVS has the advantage of providing a diagnosis much earlier in pregnancy than second-trimester amniocentesis.

Question 22

What are the preferred method to access fetal blood?

Answer 22

the preferred method to access fetal blood is Cordocentesis, or percutaneous umbilical blood sampling (PUBS)

Question 23

PUBS is usually carried out after the____ of gestation.

Answer 23

16th week of gestation and is
accomplished by ultrasound-guided puncture of the umbilical cord and withdrawal of fetal blood.

Question 24

Ultrasonography diagram

Answer 24

Question 25

One of the most important maternal serum screenings in the First and Second Trimesters are:

Answer 25

Alpha-fetoprotein screening

Question 26

What does AFP screening measure, and how is it related to amniotic fluid AFP levels?

Answer 26

AFP diffuses across the fetal membranes into maternal serum, meaning maternal serum AFP (MSAFP) levels correlate with amniotic fluid AFP levels. Noninvasive screening can be done by taking a maternal blood sample at 15 to 17 weeks post-LMP to measure amniotic fluid AFP.

Question 27

What abnormalities can maternal serum AFP (MSAFP) screening detect?

Answer 27

MSAFP screening can detect various fetal abnormalities, including neural tube defects (NTDs), trisomy 18, and Down syndrome. It provides a noninvasive approach to increase prenatal detection of these conditions.

Question 28

How can the accuracy of Down syndrome screening be improved beyond MSAFP?

Answer 28

The accuracy of Down syndrome screening can be improved by measuring serum levels of unconjugated estriol, human chorionic gonadotropin (hCG), and inhibin-A, in addition to MSAFP. This combined approach is known as the “quadruple screen.”

Question 29

What is the detection rate of Down syndrome with MSAFP alone vs. the quadruple screen?

Answer 29

MSAFP alone identifies about 40% of Down syndrome pregnancies. However, the quadruple screen (MSAFP, unconjugated estriol, hCG, and inhibin-A) increases detection to approximately 80%, with a false-positive rate of 5%.

Question 30

What is Noninvasive Prenatal Screening (NIPS) and how does it work?

Answer 30

NIPS involves analyzing fetal cells and DNA isolated from maternal blood to screen for genetic abnormalities during pregnancy. This noninvasive approach opens new opportunities for prenatal screening and diagnosis.

Question 31

What is the role of cell-free DNA (cfDNA) in Noninvasive Prenatal Screening (NIPS)?

Answer 31

Cell-free DNA (cfDNA) from the fetus enters maternal circulation and can be evaluated for mutations or aneuploidy using high-throughput sequencing. This method poses no risk of fetal loss and offers greater specificity and positive predictive value for aneuploidy detection than traditional first- and second-trimester screening.