Pre-implantation screen/policy Flashcards
Define diagnostic testing, what information may it provide?
Confirms a diagnosis in an affected person, may provide prognostic info
Define predictive testing. What are the 3 types?
Testing of unaffected individuals, usually in the absence of corroborating evidence.
Pre-symptomatic - determine whether/not a person will develop disease
Carrier - determine whether person could have affected offspring
Prenatal/pre-implantation - predict whether a child will be born with/develop disease
Define screening testing
Testing of individuals at population-level risk of disease
Define somatic testing
Testing of tumour tissue (not germline testing)
Define pharmacogenetic testing
Drug metabolism/toxicity
What are some considerations of sampling?
- purpose of testing
- biochemistry vs RNA vs RNA testing
- risk to patient (invasiveness, bleeding risk)
- abundance of sample
What is peripheral (whole) blood sample?
Where is it extracted from?
Why is it a preferred source of DNA testing?
DNA found in nucleated cells.
Extracted from white blood cells.
Because it is plentiful, easy access and minimally invasive
What is buccal cells, urine and skin samples and when are they used? What does it compare?
An alternative to blood used if difficult to get blood for some reason. Collected via swab of cheek, morning urine or biopsy. For comparison of tumour DNA to constitutional DNA.
What is chorionic villus sampling and amniocentesis and when is it used?
Chorionic villus sampling: extraembryonic tissue (placenta) at 11-14 weeks
Amniocentesis sampling: foetal cells from amniotic fluid at 15-18 weeks
What are the risks of chorionic villus sampling and amniocentesis?
- Bleeding and infection
- loss of pregnancy
- potential for incorrect results due to contamination with maternal cells
What is cell free DNA sample and when is it used?
DNA not contained by membranes but floating free in circulation can be isolated from peripheral blood. Used for non-invasive prenatal testing (NIPT) - as early as 5 weeks
How to choose which test to use?
- Which change trying to be detected?
- size (molecular or cytogenetic)
- where it occurs (single or multiple loci)
- type of change (sequence, CN, methylation)
- volume of samples being tested
- purpose of testing (known or unknown mutation)
What is targeted and untargeted testing?
Targeted testing: specific alleles or CNVs are tested for the mutation being looked for is there no not
Untargeted testing: whole or multiple genes, whole genome; more than one disease variant may be found, but which ones are causative?
Define pathogenicity
Whether the variant is able to cause the disease
What is the 5 tier classification system of pathogenity?
Class 1 - benign Class 2 - likely benign Class 3 - Uncertain significance Class 4 - likely pathogenic Class 5 - Pathogenic
What types of evidence is used to determine pathogenicity?
- Public resources
- in silico prediction
- functional studies
- segregation of genotype with disease
What’s informed consent? What does it have implications for?
The process by which a healthcare provider informs a patient of their treatment options, risks and benefits etc.
Has implications for non-paternity and relatedness, extended family and insurance.
What are some ethical challenges of informed consent?
- life choice (marriage, family, occupation)
- continuation of pregnancy
- access to insurance
- testing of a family member (should the others know? Do they want to know?)
What is population screening?
Involves test being offered to all individuals in an eligible group, as part of an organised program. Screening offered at recommended intervals. Aim of bringing health benefits to community. Based on WHO principles of screening
What are the criteria of population screening?
- targeted health condition
- screening and assessment test
- treatment and management of individuals diagnosed
- requires more benefit than harm to target population
- strong evidence based
What are some types of population screening?
- Cancer (breast, bowel, cervical)
- pre-implantation screening
- prenatal screening
- newborn bloodspot screening
What is prenatal screening?
Routine health assessments for the mother and baby, including tests for maternal diabetes and infections, ultrasounds to access fetal growth and placental placement, blood tests for iron levels and rhesus factor, screening for chromosome and structural anomalies.
How is prenatal diagnosis tested?
With cells collected via amniocentesis or chorionic villus sampling:
- fetal DNA in maternal DNA
- karyotyping (chromosome)
- fluorescence in situ hybridisation
- DNA testing
What is the newborn bloodspot screening test? How many rare genetic conditions are approximately tested?
Almost every baby in WA is screened through the WA Newborn Bloodspot screening program (Guthrie test). Via tandem mass spectrometry testing for ~25 rare genetic conditions
What are the limitations of the newborn bloodspot screening test?
- screening test only (indicates possibility only, more testing needed)
- not all affected will be identified via screening
- accuracy of test varies
What is preimplantation genetic testing?
One or more cells from an embryo are removed/biopsied and their chromosome/DNA tested for genetic abnormality. For people at risk of passing on a serious condition, genetic testing is done before implantation of an embryo
What is preimplantation genetic diagnosis (PGD)?
One or more cells from an embryo are tested for the presence of gene/s that may harm the embryo. No and normality of chromosomes (also known as aneuploidy screening)
What can PGD test for?
- single gene (monogenic) conditions
- sex-linked conditions
- translocations
What is the reproductive technology council? What does it consider
Approval from the WA reproductive tech countril (RTC) needed before a fertility clinic can create embryos for PGD.
Considers:
- the risk and severity of condition
- how safe and reliable the test is
- the impact of the condition on the child and family
How do you seek PGD approval?
Discussion:
- with genetic counselling
- may follow a GP
Consultation with a fertility clinic:
- genetic counsellor will inform
- GP or specialist referral required for IVF
For single gene disorders, fertility clinic will apply for RTC on your behalf (~1 month)
What are the PDG process steps?
- discussion with genetic counsellor
- IVF clinic consultation
- IVF clinic counselling
- Feasibility test
- application for PGD
What is IVF?
In vitro fertilisation: egg is fertilised in lab through natural sperm penetration
What is ICSI?
Intracytoplasmic sperm injection: single chosen sperm is inserted into an egg in lab. Preferred method for PDG
What are the steps for IVF/ICSI for PDG?
- Fertility drugs for women (stimulate ovulation and eggs)
- Blood and ultrasound tests (check woman’s follicle development - egg collection can be timed)
- egg collection
- fertilisation (IVF/ICSI)
- Biopsy of cells at 3 days
- Lab analysis
- Embryo freezing
- Transfer
What is the accuracy and risks of PGD?
about 98% accurate
risks:
- health risks of the IVF cycle
- embryo may not develop
- not all embryos suitable after biopsy
- may not be any unaffected embryos for transfer
- test results may be inconclusive
- no pregnancy after transfer
