-
How many DNA bases are packed around a histone?
140-150 DNA bases
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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
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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
- Stabilizes 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?
Posteriorly
-
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
- "SNOUT"
-
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
- "SPIN"
-
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?
- 1. Ultrasound
- 2. PAPP-A
- 3. BhCG
-
What prenatal tests can be done in the second trimester?
- 1. Triple screen
- 2. Quad screen
- 3. Penta screen
- 4. Amniocentesis
- 5. Cordocentesis
-
What does MSAFP stand for?
Maternal serum alpha fetal protein
-
Which of the second trimester tests are NOT invasive?
- Triple screen
- Quad screen
- Penta screens
- (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?
1/270
-
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?
nuchal translucency
-
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
- 3. Stillbirth
-
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?
3 weeks
-
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?
- 1. Trophoblasts
- 2. Lymphocytes
- 3. Granulocytes
- 4. Stem cells
- 5. Nucleated erythrocytes
-
Which fetal cell that is found in maternal blood is preferred for testing purposes?
nucleated erythrocytes
-
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?
- Kleihaur-Betke test
- 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?
1/100
-
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?
gestational age
-
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?
0-40 mcg/L
-
What is the normal level of MSAFP in a woman that is 10-15 weeks pregnant?
10-150 mcg/L
-
When do AFP levels in fetal serum peak?
around week 14
-
AFP in the amniotic fluid is normally found in (high or low) concentrations
Low
-
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
- Diabetic women
- Obeses women
-
Lowest levels of AFP are seen in this ethnicity
Asian women
-
AFP is checked by which test?
Amniocentesis
-
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...
amniotic fluid
-
Which gene is important in supressing cancer cells?
P53
-
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...
- High MSAFP
- Normal UE3
- Normal B-hCG
-
In a triple screen trisomy 21 would show...
- Low MSAFP
- Low UE3
- High B-hCG
-
In a triple screen trisomy 18 would show...
- Low MSAFP
- Low UE3
- Low B-hCG
-
In a triple screen molar pregnancy would show...
- Low MSAFP
- Low UE3
- Very high B-hCG
-
In a triple screen multiple fetuses would show...
- High MSAFP
- Normal UE3
- High B-hCG
-
In a triple screen fetal death would show...
- High MSAFP
- Low UE3
- Low B-hCG
-
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?
80%
-
What molecules does a penta screen test?
- 1. MSAFP
- 2. UE3
- 3. B-hCG
- 4. Inhibin A
- 5. hyperglycosylated hCG (h-hCG)
-
Elevated levels of h-hCG/ invasive trophonlast antigen are associated with..
Trisomy 21
-
What are the risks of amniocentesis?
- miscarriage 1/200
- 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?
- 11 weeks
- associated with respiratory effects
-
How much amniotic fluid is taken out during an amniocenteis?
15-20mL
-
How long are amniocytes typically cultured?
7 days
-
What information can be derived from an amniocentesis?
- Biochemical assays
- 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?
12 weeks
-
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?
FISH
-
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?
48-72 hours
-
Which phase of mitosis do the fetal cells need to be arrested in for karyotypes?
metaphase
-
How long do FISH techniques take?
2 days
-
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?
- 1. Breathing
- 2. Movement
- 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
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