W12 l1 Thues Genetic screening Flashcards
type of genetic screening/testing
-Preimplatation genetic
-Prenatal
-Postnatal
type of screening in preimplantation screening
- Polar body or embryo biopsy
- Karyotyping
- Polygenic embryo selection
Type of screening in prenatal screening
- Maternal blood (fetal cell sorting & cell free DNA)
- Fetal blood sampling
- Invasive (Chorionic Villus Sampling & amniocentesis)
Type of screening in post natal
- Neonatal
- Childhood (paternity, single gene, late onset disease)
- Adult (carrier, predictivepresymptomatic, personalise
treatment, direct to consumer testing)
Maternal Blood
Fetal cell sorting vs cell free DNA
Cell free - very accurate for Trisomy 21 and 18, not as much for trisomy 13 - failure rate up to 4%)
-Fetal cells (70% of pregnancies) in very low numbers (cells from previous pregnancy may remain). Identify cells using Y probe (males) or different surface markers (females).
Fetal blood sampling
Often from umbilical cord, can be from blood vessel in liver or heart of fetus
Risky:
Bleeding (20 - 30%)
Heart rate changes (5 - 10%)
Infection
Amniotic fluid leak
Possible death (1.4% pre 28 weeks)
-Verify genetic / chromosomal abnormalities, and identify
other diseases (anaemia, oxygen levels, infection, Rh status)
Chorionic Villus Sampling
- Performed at 10 - 13 weeks
- Spontaneous abortion rate 5% (increased 0.8% by CVS)
- 10 - 30 mg chorion required
- Separate maternal and fetal tissue
- Mosaicism
Amniocentesis
- Performed at 15 - 20 weeks
- Spontaneous abortion rate 3.2% (increased 0.3% by AMN)
- 200 ml amniotic fluid (at 16 wk)
- Recommended >37 years
Key consideration for invasive test
-Testing > 24 weeks can have better diagnosis and the law allows for abortion if at least 2 Drs agree it is appropriate.
-Considerations: Medical, current/future physical, psychological, social.
Neonatal Guthrie - heel prick
Look at protein level
-Phenylketonuria (high phenylalanine)
-Cystic fibrosis (high trypsinogen) - followed by sweat test (increased NaCl)
-Hypothyroidism (high thyroid stimulating hormone)
+ 25 others (in Victoria)
Childhood Paternity testing
Human Genetics Society of Australia recommends consent from both parents, but mother is not required for testing . Test for a number of SNPs.
Childhood genetic disease testing
-Presymptomatic and predictive testing <18 years of age (at own or parent / guardian request) does not occur.
Current recommendations for late onset diseases:
-Only for conditions for which there is potential medical benefit (surveillance, prevention strategies or medical interventions) in the immediate future.
Adult genetic testing
Carrier testing - family planning (esp. for couples with affected children)
Presymptomatic - (at-risk family) e.g. Huntington disease, various cancers
Predictive (risk of developing disease) cumulative SNPs associated with disease risk.
Treatment testing - Given a polygenic disease, specific treatments may have higher success rate for specific genotypes.
Why do we carry preimplantation screening
-Couples with repeated pregnancy loss due to genetic abnormality.
-Tissue match (for transplantation) for sick sibling (preimplantation tissue typing)
-Couples with child with genetic disease.
- sex selection (in AU only for X linked condition)
Polar body biopsy
Predicting genotype of eggs from carrier mothers.
No detrimental effects - not used in fertilisation.
