Genetic and Prenatal Testing Flashcards
What are the two types of prenatal genetic testing?
Screening tests and diagnostic tests
What do prenatal screening tests do?
Estimate chances that a fetus has an aneuploidy or other disorder
What are the main prenatal screening tests?
First Trimester Screen (Mother) Triple Screen (MSAFP) Quad Screen (Mother) Carrier Screening (Mother and/or Father) Cell-Free DNA Testing (Fetus) Ultrasound (both screening and diagnostic)
What do prenatal diagnostic tests do?
Confirm if a fetus actually has a certain disorder
What are the main prenatal diagnostic tests?
Amniocentesis Chorionic Villus Sampling (CVS) Percutaneous umbilical blood sampling Preimplantation genetic diagnosis Ultrasound (both screening and diagnostic)
These tests use cells from the fetus or placenta
First Trimester Screen
11-14 weeks (1st Trimester)
Screens for trisomy 13, 18, and 21
Measures nuchal translucency (via US) and B-hCG and PAPP-A (via maternal serum)
First Trimester Screen Interpretations
Trisomy 21: increased NT, increased B-hCG, decreased PAPP-A
Trisomy 13 and 18: increased NT, decreased B-hCG, and decreased PAPP-A
Triple Screen
15-20 weeks (2nd Trimester)
Screens for trisomy 13, 18, 21, and NT defects
Measures maternal serum for MSAFP + uE3 + hCG
Quad Screen
Same as triple screen + checks for inhibin A
Triple Screen Interpretation
Trisomy 21: decreased MSAFP, decreased uE3, increased hCG
Trisomy 13 and 18: decrease in –> MSAFP, uE3, hCG
Nural tube defect (NTD): Large increase in MSAFP
What does MSAFP stand for?
maternal serum alpha-fetoprotein
What does uE3 stand for?
unconjugated estriol
What does hCG stand for?
Human chorionic gonadotropin
What does NTD stand for?
Nural tube defect
What does NT stand for?
Nuchal translucency
Cell-Free DNA
After 10 weeks of gestation, circulating free DNA (cfDNA) are released from placenta into maternal circulation. Can be used to screen for trisomy 13, 18, and 21 using next generation sequencing
Also called NIPT or NIPS: Non-Invasive Prenatal Testing/Screening
Ultrasound
20 weeks
Screens for anatomical alterations and NTDs
Chorionic Villus Sampling
10-13 weeks
Biopsy of the chorionic villi of placenta
Chromosome analysis (aneuploidy, translocations, deletions, duplications, single-gene disorders)
Miscarriage risk slightly higher than amniocentesis
Amniocentesis
16-20 weeks
Needle obtains amniotic fluid which contains cells of fetal origin which can be used for karyotype, FISH, comparative microarray analysis.
Risks infection and miscarriage
Preimplantation genetic diagnosis (PGD)
~5 trophectoderm cells removed from blastocyte-stage embryo (5-6 days)
For in vitro fertilization
Percutaneous umbilical blood sampling
At or after 18 weeks
Sample of feta blood withdrawn from umbilical cord
Rarely used, has been largely replaced by other methods
What does PAPP-A stand for?
Pregnancy-associated plasma protein A
What can Karyotyping test for?
Aneuploidy + Large CNV
What does CNV stand for?
Copy number variant; when the number of copies of a particular gene varies from one individual to the next
What can FISH test for?
Aneuploidy + Large CNV + Small CNV
What can chromosomal microarray test for?
Aneuploidy + Large CNV + Small CNV
What can next gen sequencing and targeted sequencing test for?
Aneuploidy + Large CNV + Small CNV + single-gene variant
Single gene sequencing
Helps to identify a single gene or short list of genes pertaining to a suspected syndrome
Good for identifiable symptoms or known family history
Phenotype specific panel testing
Tests for a group of genes related to phenotypes
Good for when an identifiable group of features is present but not easily specific to one particular syndrome or gene
Whole-Exom Sequencing (WES)
Gives data on all protein-coding regions of the genome
Whole-Genome Sequencing (WGS)
Gives data on entire genome
When are the different trimesters?
First trimester: weeks 1-12
Second trimester: weeks 12-26
Third trimester: weeks 27 until the end of pregnancy
