Basic genetics Flashcards
what are chromosomes made of?
Chromosomes are thread
-like structures located
inside the nucleus of animal and plant cells. * Each chromosome is made of protein and a single
molecule of deoxyribonucleic acid (DNA)
Karyotype - what is this?
(kary has chromosomes)
we don’t usually order these - it is a specific test. If there is an issue, you need to test both partners.
- Cytogenetic test (examines chromosomes)
- identification of numerical and structural chromosomal
abnormalities.
Euploid (correct # of chromosomes) or ANEUPLOID (missing or additional chromosome)
- An individual with a normal number of chromosomes would
be considered EUPLOID. (46 XX or 46 XY). - If there is an abnormality regarding the chromosomes,
this would be considered ANEUPLOIDY (image).
Karyotype…
Limitations
cost, TAT (turn around time) 3+ weeks to result, lab quality/resolution, pt history (bone marrow transplant) - instead of blood cells, need check or skin cells to interpret
Genetic Carrier Screening
- Determines the risk for passing an inherited genetic condition.
- Done preconception, can allow the couple to decide how to best grow their family.
- Genetic conditions are dominant (affected individual) or recessive (carrier) & x-linked
- Screening offered preconception focuses on recessive (carrier) & x-linked genetic conditions.
- Examples of recessive diseases:
- Cystic Fibrosis, Spinal Muscular Atrophy (SMA), Hemoglobinopathies, etc…
- Examples of X-linked disease:
- Fragile X
autosomal recessive conditions
Two copies of an abnormal gene must be present in order for
the disease or trait to develop - 25% unaffected 50% carriers (usually not symptomatic), 25% affected
Horizon - what are sperm providers tested for?
- SPRING works with Natera (this is the lab that runs the screening)
- Natera’s carrier screening test is named Horizon.
- Expanded Carrier screening that SPRING utilizes:
- Horizon-up to 421 Carrier Screening panel
- Egg provider: includes X-linked conditions
- Sperm provider: Not screened for X-linked conditions
- Offered to all patients by Provider
- PN reviews option and helps to schedule/follow up
how to inform patients of this option
- Everyone is expected to be a carrier of at least one genetic condition, most are healthy (60% screen positive)
- Both partner positive for recessive condition : ~1 in 4 chance of an affected pregnancy
- X-linked condition:
- Boys: 1 out of 2 chance for boys to be affected
- Girls: 1 out of 2 chance for girls to be carriers
- Appropriate for all patients of any and all ethnicities (pan-ethnic)
- Many conditions being tested for may not be life altering
- Family history is important to determine what other genetic testing could be relevant
- Encourage discussion of results with family members
- Genetics counselors can advise patient on results and options
carrier screening completed at an outside facility
- Some comparable panels will be accepted per ethnicity screening of the couple – see chart CN11
- Report must be uploaded to the patient documents
- Utilize the test name “Genetic Carrier Screening” that are not Horizon.
- Add details under remarks on the lab panel –panel name & number of conditions tested.
- GC must be tasked to review results, inc. document title and page number of CR result, if applicable.
- The GC will review report/input and sign off in Blood/Lab tests.
- If acceptable expanded carrier screening (ECS) panel completed (as per Table 1 in CN11) it is NOT recommended that they repeat screening.
- Checklist item cannot be checked as completed unless waiver signed and review/sign-off completed by APP (NP/PA).
- For patients selecting a sperm donor, the carrier screening results of IP/donor MUST be cross checked by an APP/GC.
- CA—task APP, NP or PA for your site, to review CR-results prior to patient purchasing.
- NYC- formal counseling by Spring GC or GeneScreen is required prior to purchase. This must be uploaded to chart.
- PDX- TBD
we don’t really want ppl to repeat screening if they’ve had it already bc it leads to confusion
what is PGT testing?
(embryo pagent)
- Preimplantation genetic testing (PGT) can be done to evaluate an embryo prior to transfer.
GC calls patient with:
- Embryo testing,(PGT), POC(Anora) and
Panorama (NIPT) results. - Can provide risk assessment/education
- PGT options
- Donor results, etc
formal apt.
- $300, full consult ~ 1hr, insurance not currently
accepted unless Progyny - $100, for 15min call, if indicated per ECS, etc..
- Send order to Finance to obtain auth for
Progyny or to provide CL (cost letter) to pt. prior to appt.
Genetics Consult Types - formal
Paid Consult
* Spring Genetics Counselor
* Outside Genetics Counselor
* Genescreen (NYC)
* Per Insurance or patient preference
Genetics Consult Types -Genetics Information Session (GIS)
- Free Consult (~15 min or less)
- Testing Lab’s GC (Natera)
PGT-A : Aneuploidy testing ** Most common**
(A line)
This only tells if the chromosomes are lined up accurately -
Identify/transfer only Euploid embryos (46 XY or XX)
what does PGT-M test for?
(my genetic disease)
monogenic (single gene mutations) conditions - Identify embryos affected with inherited genetic disease
Must be aware of condition to develop proper test/probe for the family
PGT-SR - what does it test for? and what are the 3 types?
(sir, that’s structure)
(sir, that’s RIR)
structural rearrangement
if patient had a child or pregnancy with a chromosome rearrangement or if patient or partner are a carrier of an:
Inversion
Reciprocal translocation is Balanced/Unbalanced
Robertsonian translocation-
X-linked conditions - what are the % for boys and girls?
We only test the egg provider - we don’t want to diagnose the sperm carrier. Gene causing the trait or the disorder is located on the X chromosome
(sperm provider only has one X, so if it’s on the X, the male is affected)
unaffected son - 25%, affected son 25%, unaffected daugher - 25%, carrier daughter 25%
PGT - at what stage of development can we do this? and what day is this? (think where the tissue is coming from)
It has to grow to the blastocyst phase before we can test it.
- Trophoblastic cells (eventually become the placenta - NOT the fetal cells) can be removed from a blastocyst (day 5/6 embryo) and sent for testing.
what are the indications for PGT? (4 of them)
- Recurrent Miscarriage
- Advanced maternal age
- Known Chromosomal Condition
- Known genetic disease
horizon - how quickly to get results?
Results in ~ 2 weeks
Can Test one partner first
* Test other partner if the first screens positive
* Test couple together
* Results needed prior to treatment – egg freezing optional
* Waiver must be signed if declining
Inversion
a segment of a chromosome is flipped and reinserted upside down.
Reciprocal translocation
pieces of genetic material break off from two different chromosomes and swap places. Balanced/Unbalanced
Robertsonian translocation
(join robert)
Robertsonian translocation-two chromosomes join together to form one large chromosome, giving an overall chromosome count of 45 instead of 46.
CR screening waiver required
- CR screening waiver required depending on panel/mutations screened if not deemed comparable with currently offered screening.
- If patient/partner completed a panel that is not listed in Table 1 CN11.
- If the patient and partner both completed CR screening utilizing different panels, waiver will need to be signed.
when is karotype ordered?
(Kary and BF are recurrent and DOR)
- Not routinely ordered but may be indicated for:
- Recurrent pregnancy loss (female/male) - usually 1st trimester lost
- Unexpected embryologic outcome (female/male)
- Suggested on PGT-A results
- High suspicion form family history (female/male)
- Severe DOR in younger population (female)
- Severe male factor infertility (male)
PGT-A - who does it help?
increases chance of live birth in older women or those with recurrent miscarriage
Family balancing
