Basic genetics

Question 1

what are chromosomes made of?

Answer 1

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)

Question 2

Karyotype - what is this?

(kary has chromosomes)

Answer 2

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.

Question 3

Euploid (correct # of chromosomes) or ANEUPLOID (missing or additional chromosome)

Answer 3

• 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).

Question 4

Karyotype…
Limitations

Answer 4

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

Question 5

Genetic Carrier Screening

Answer 5

• 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

Question 6

autosomal recessive conditions

Answer 6

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

Question 7

Horizon - what are sperm providers tested for?

Answer 7

• 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

Question 8

how to inform patients of this option

Answer 8

• 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

Question 9

carrier screening completed at an outside facility

Answer 9

• 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

Question 10

what is PGT testing?

(embryo pagent)

Answer 10

• Preimplantation genetic testing (PGT) can be done to evaluate an embryo prior to transfer.

Question 11

GC calls patient with:

Answer 11

• Embryo testing,(PGT), POC(Anora) and
  Panorama (NIPT) results.
• Can provide risk assessment/education
• PGT options
• Donor results, etc

Question 12

formal apt.

Answer 12

• $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.

Question 13

Genetics Consult Types - formal

Answer 13

Paid Consult
* Spring Genetics Counselor
* Outside Genetics Counselor
* Genescreen (NYC)
* Per Insurance or patient preference

Question 14

Genetics Consult Types -Genetics Information Session (GIS)

Answer 14

• Free Consult (~15 min or less)
• Testing Lab’s GC (Natera)

Question 15

PGT-A : Aneuploidy testing ** Most common**
(A line)

Answer 15

This only tells if the chromosomes are lined up accurately -

Identify/transfer only Euploid embryos (46 XY or XX)

Question 16

what does PGT-M test for?

(my genetic disease)

Answer 16

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

Question 17

PGT-SR - what does it test for? and what are the 3 types?

(sir, that’s structure)

(sir, that’s RIR)

Answer 17

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-

Question 18

X-linked conditions - what are the % for boys and girls?

Answer 18

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%

Question 19

PGT - at what stage of development can we do this? and what day is this? (think where the tissue is coming from)

Answer 19

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.

Question 20

what are the indications for PGT? (4 of them)

Answer 20

• Recurrent Miscarriage
• Advanced maternal age
• Known Chromosomal Condition
• Known genetic disease

Question 21

horizon - how quickly to get results?

Answer 21

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

Question 22

Inversion

Answer 22

a segment of a chromosome is flipped and reinserted upside down.

Question 23

Reciprocal translocation

Answer 23

pieces of genetic material break off from two different chromosomes and swap places. Balanced/Unbalanced

Question 24

Robertsonian translocation

(join robert)

Answer 24

Robertsonian translocation-two chromosomes join together to form one large chromosome, giving an overall chromosome count of 45 instead of 46.

Question 25

CR screening waiver required

Answer 25

* 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.

Question 26

when is karotype ordered? (Kary and BF are recurrent and DOR)

Answer 26

* 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)

Question 27

PGT-A - who does it help?

Answer 27

 increases chance of live birth in older women or those with recurrent miscarriage Family balancing