Card Set Information
Genetics prenatal screening
Prenatal screening, genetics
How many DNA bases are packed around a histone?
140-150 DNA bases
In which direction does DNA replication and RNA synthesis proceed?
From the 5' end to the 3' end
DNA polymerase adds free nucleotides to which end of the new DNA strand?
the 3' end
What is the funtion of replication bubbles?
To allow DNA replication to happen faster
Where does RNA polymerase bind to begin mRNA synthesis?
Promoter site on the DNA
The template strand is also referred to as...
the antisense strand
What is the 5' cap?
Chemically modified guanine nucleootides added to the 5' end of new RNA molecule
Keeps mRNA from being degraded during synthesis
What is the Poly-A tail?
100-200 adenine bases added to the 3' end of mRNA
What are housekeeping genes?
Genes transcribed in all cells of the body that encode products that are required for a cell's maintenance and metabolism
Name three important transcription factors
Homeobox-containing genes (HOX, PAX)
SOX genes (SRY)
GLI (involved in hedgehog signalling pathways)
What are HOX genes?
Highly conserved developmental genes
3' genes expressed anteriorly and earlier than 5' genes
Forms a posterior/anterior axis
Effects of HOX genes in development
HOX gene products are molecular switches (transcription factors)
Promotes cell division, adhesion, apoptosis and cell migration
Where will descendents of SHH show up?
Diagnostic sensitivity compares
the true positives and false negatives in a clinical test
What are characteristics of a highly sensitive test?
The number of false negatives is very low
A negative result is a reliable way to rule OUT a disease
Diagnostic specificity compares...
True negatives to falso positives in a clinical test
Characteristics of a highly specific test
The number of false positives is very low
A positive result is a reliable way to rule IN a disease
What prenatal tests can be done during the 1st trimester?
1. Chorionic Villus Sampling (CVS)
2. First trimester screen (ultrasound, PAPP-A and BhCG)
When does BhCG first appear in serum?
At 2 weeks
What does a first trimester screen consist of?
What prenatal tests can be done in the second trimester?
1. Triple screen
2. Quad screen
3. Penta screen
What does MSAFP stand for?
Maternal serum alpha fetal protein
Which of the second trimester tests are NOT invasive?
(these are maternal blood tests)
Which tests can be done in the third trimester?
1. Biophysical profile
2. Fetal movement monitoring
3. Contraction stress test
4. Glucose challenge screening and glucose tolerance test
5. Group B strep test
What is the most common risk threshold?
What are the current ACOG guidelines for prenatal testing?
1. All pregnant women should be offered screening of down syndrome, regardless of maternal age
2. Ideally should be done BEFORE week 20
3. Non-invasive screening tests are much more reliable than they once were
When are non-invasive screening tests the most reliable?
Before week 20
What information can you obtain from an ultrasound?
1. Placental and fetal size
2. Multiple fetuses
3. Placental abnormalities
4. Abnormal presentations of the fetus
5. Estimation of fetal age
Screening for what is useful to detect Down Syndrome in the late first trimester?
When/ How is PAPP-A measured?
From the maternal serum in the 1st trimester
What are low levels of PAPP-A associated with?
1. Trisomy 13, 18 and 21
2. Small for gestational age
What are high levels of PAPP-A associated with?
Large for gestational age
Where is B-hCG produced and where is it found?
In the syncytiotrophoblast and enters the maternal bloodstream
What does B-hCG do?
It maintains the hormonal activity of the corpus luteum during pregnancy
When does B-hCG show up in urine?
In which trimesters can B-hCG be used for screening?
1st and 2nd trimesters
When can fetal cells be detected in the maternal blood stream?
As early as 8 weeks
What types of fetal cells can be found in the maternal blood stream?
4. Stem cells
5. Nucleated erythrocytes
Which fetal cell that is found in maternal blood is preferred for testing purposes?
Why are nucleated erythrocytes perferred for prenatal screening?
Because they are short-lived in the blood stream
(You know you're not collecting a sample from a pervious pregnancy)
What does a KB test detect?
Detects maternal hemmorage and helps determine amount of Rhogam to use in erythroblastosis fetalis
What is Chorionic Villus Samping used for?
To obtain a karyotype
When is CVS performed?
between the 10th and 12th weeks
What is the risk of miscarriage for CVS?
What molecules does a triple screen test?
When is a triple screen performed?
In the second trimester around the 16th week
What does interpretation of the triple screen rely heavily upon?
What is MSAFP?
Maternal Serum Alpha Fetal Protein
A large serum glycoprotein
Where is MSAFP synthesized?
In the fetal liver, umbilical vesicle and gut
What is the normal level of MSAFP in a non-pregnant woman or man?
What is the normal level of MSAFP in a woman that is 10-15 weeks pregnant?
When do AFP levels in fetal serum peak?
around week 14
AFP in the amniotic fluid is normally found in (high or low) concentrations
High levels of AFP in the amniotic fluid can indicate...
Neural tube defects or abdominal wall defects
Higher levels of AFP are seen in these women, regardless of fetus
African american women
Lowest levels of AFP are seen in this ethnicity
AFP is checked by which test?
High levels of AFP in non-pregnant adults are associated with...
1. Testicular or Ovarian cancer
2. Liver disease
3. Alcohol abuse
AChE should never be found in...
Which gene is important in supressing cancer cells?
Where can UE3 be detected?
In mother's blood and urine
How do the levels of UE3 change in the third trimester?
They normally increase throughout the third trimester
A sudden drop indicates a threatened fetus
Low levels of UE3 are associtated with
Trisomy 18 and 21
In a triple screen a neural tube defect would show...
In a triple screen trisomy 21 would show...
In a triple screen trisomy 18 would show...
In a triple screen molar pregnancy would show...
Very high B-hCG
In a triple screen multiple fetuses would show...
In a triple screen fetal death would show...
What molecules does a quad screen test for?
Where is inhibin A secreted?
by placenta and corpus luteum
What are high levels of inhibin A associated with?
Increased risk for trisomy 21 and preterm delivery
What does inhibin A do?
Down regulates FSH synthesis and inhibits its secretion by the anterior pituitary gland
Which precentage of pregnancies with chromosomal abnormalities can be detected with a quad screen?
What molecules does a penta screen test?
4. Inhibin A
5. hyperglycosylated hCG (h-hCG)
Elevated levels of h-hCG/ invasive trophonlast antigen are associated with..
What are the risks of amniocentesis?
maternal Rh sensitization
When can amniocenteis be performed?
In the second trimester between weeks 16 and 20
When is the earliest amniocentesis can be performed and why is this not advised?
associated with respiratory effects
How much amniotic fluid is taken out during an amniocenteis?
How long are amniocytes typically cultured?
What information can be derived from an amniocentesis?
DNA-based diagnosis (PCRs)
Chromosome analysis (karyotype (slow), FISH (fast))
Cordocentesis is also referred to as
Percutaneous umbilical blood sampling (PUBS)
When is the earliest PUBS can be performed?
From where is the fetal blood obtained?
Umbilical vein, near the placenta
What is Cordocentesis used for?
For rapid diagnosis of blood diseases
and to distinguish between true and falso fetal mosaism
When is the earliest fetal transfusion can be performed?
around 20- 22 weeks
Which procedure can be performed on ANY fetal cell?
What are advantages of FISH?
Can be used on interphase (you don't have to wait as long)
Able to detect small deletions, insertions and chromosomal rearrangements
What is the resolution of FISH?
1Mb (this is generally not possible in karyotyping)
How long must cells be cultured in a karyotype?
Which phase of mitosis do the fetal cells need to be arrested in for karyotypes?
How long do FISH techniques take?
In how many chromosomal pairs does FISH detect problems?
In 9 of the 23 chromosomal pairs
When is Biophysical Profiling performed?
In the third trimester, after 24-26 weeks
What are the 5 attributes of biophysical profiling?
3. Muscle tone
4. Heart rate
5. Amniotic fluid
Biophysical profile: Normal breathing
1 breathing episode in 30 minutes
Biophysical profiling: movement
2 or more moving episodes in 30 minutes
Biophysical profiling: Muscle tone
1 or more episodes of flexion or extension of limbs
Biophysical profiling: heart rate
2 or more episodes of reactive heart accelerations in 20 minutes
Biophysical profiling: Amniotic fluid
1 or more adequate pockets of amniotic fluid