Exam 4 - PGT (cont.) and Birth Defects Flashcards
What can be determined from PGS (PGT-A) and PGD (PGT-M)?
PGS/PGT-A : number of chromosomes, aneuploidy, sex, mosaicism, etc.
PGD/PGT-M: specific gene mutations/single gene disorders
What are arguments in favor of universal PGT-A?
decreased termination due to aneuploidy
increased pregnancy rates
reduced miscarriage rates
What is aCGH?
array comparative genomic hybridization
Why does PGT-A increase ongoing pregnancy rates and decrease pregnancy loss rate?
embryos with aCGH testing prior to transfer means only euploid embryos get transferred
What are some considerations for PGT?
genetic counseling must include alternate strategies (such as donor gametes or adoption)
diagnostic methodology may be expensive
biopsy may damage embryo
not all genetic abnormalities can be diagnosed
there may be no “unaffected” embryos to transfer
controversial applications (gender selection, savior siblings, designer babies)
misdiagnosis may result from mosaicism
prenatal diagnosis is recommended for confirmation of PGS/PGD
What is a birth defect?
abnormality of structure, function, or metabolism that is present at birth and results in a physical or mental disability/death
What is a congenital defect?
any physical anomaly which is recognizable at birth
How common are birth defects?
about 120,000 babies (1 in 33) in the US are born with birth defects each year
leading cause of death in the first year of life
What are the three causes of birth defects?
chromosomal defects, single gene defects, and environmental factors
What are chromosomal birth defects?
too many or too few chromosomes (aneuploidy) such as trisomy 21, 13, and 18
What are single gene defects?
mutation in a gene (or multiple genes) causes a disorder
ex:
achondroplasia, cystic fibrosis, hemophilia
What are environmental factor birth defects?
teratogens (environmental substances that cause birth defects)
ex:
alcohol (cause fetal alcohol syndrome)
drugs/medication (cocaine, acne medication isotretinoin)
infections (STDs)
How can birth defect risk be reduced?
consult a genetic counselor if birth defects are present in family history, avoid smoking/alcohol/drugs, STD screening, multivitamin with folic acid
What is the recommended folic acid dose?
400 micrograms to 4 mg
When does neural tube formation occur? Why is this important?
15-28 days of development (from fertilization)
often before women know they are pregnant so defects can be attributed to environmental (or genetic) factors
What are the two neural tube defects we discussed? How do they happen?
anencephaly:
- upper part of neural tube does not close all the way
- baby is born with parts of brain and skull missing
spina bifida:
- can happen anywhere along the spine where lower part of the neural tube doesn’t close all the way
- causes physical and mental disability that range from mild to severe
Failure of the neural plate to fuse in what regions cause anencephaly and spina bifida?
anencephaly: failure to close in region 2
spina bifida: failure to close in region 5
What processes are folic acid important for?
DNA synthesis, DNA repair, DNA methylation, cofactor in biological reactions, rapid cell division and growth, preventing major birth defects in brain and spine such as anencephaly and spina bifida
How much does folic acid decrease risk of neural tube defects?
decrease risk by 50-70%
How has the government tried to increase women’s intake of folic acid?
1992, US Public Health Service recommended women of childbearing age increase consumption of folic acid to reduce spina bifida and anencephalus
1996, FDA authorized that all enriched cereal grain products be fortified with folic acid
What ways can birth defects be diagnosed before birth?
blood tests, ultrasound, chorionic villus sampling, amniocentesis
How can blood tests be used to test for birth defects?
Non Invasive Prenatal Testing (NIPT) done as early as 7 weeks from LMP
uses cell free fetal DNA:
- primary source in maternal circulation though to be apoptosis of placental cells (syncytiotrophoblasts)
- most reliably used for sex determination and sex linked disorders, potential for gender discrimination
- most commonly used to diagnose trisomy 13, 18, and 21 and single gene defects of paternal origin
How is ultrasound used in each trimester?
first trimester: establish dates of pregnancy, detect heartbeat by 7 weeks from LMP, fetal movement at 7-8 weeks, number of fetuses, ectopic pregnancy or miscarriage
second trimester: fetal anatomy for presence of abnormalities, discover sex of fetus around 14 weeks
third trimester: monitor fetal growth, check amount of amniotic fluid, determine position of fetus and placenta
What is CVS?
chorionic villus sampling
- performed between 10-12 weeks from LMP (when placenta is fully functional)
- sample of placental tissue taken under ultrasound guidance (contains same genetic info as fetus and can be tested for chromosomal abnormalities and some other genetic defects)
- does not provide info on neural tube defects
