Board Review Course

Question 1

What are the general instructions for pedigree development as outlined by the standard for pedigree nomenclature

Answer 1

key should contain all info relevant to interpretation of pedigree
for clinical pedigrees
need to include: name of proband, family names/initials as appropriate, name/title of person recording pedigree, historian, date of intake/update, reason for taking pedigree, ancestry
limit identifying information to maintain confidentiality and privacy

Question 2

What is the designation for stillbirth on pedigree? spontaneous abortion? ectopic pregnancy?

Answer 2

stillbirth: SB w GA and karyotype if known
spontaneous abortion: SAB w GA/gender if known
Ectopic: ECT

Question 3

What is the difference between no children by choice or reason unknown vs infertility

Answer 3

no choice or reason unknown: one line under individual w reason if known (ex: tubal/vasectomy)
infertility: two lines under individual w reason if known (ex: azoospermia/endometriosis)

Question 4

What is the difference on a pedigree with adoption into a family and adoption out of a family

Answer 4

Into: dotted lines (aka they are not biologically related to their parents)
Out of: solid line (aka their biological child was given up for adoption)

Question 5

How would you designate someone who is a sperm/egg donor on pedigree? If someone is a surrogate? If a women is BOTH the ovum donor and surrogate?

Answer 5

sperm/egg donor: D
surrogate: S
BOTH: she will only be referred to as a donor; pregnancy symbol and its line of descent are positioned below the woman who is carrying the pregnancy

Question 6

How would you write, on a pedigree, an asymptomatic/presymptomatic carrier

Answer 6

line down the center of the pedigree symbol (square, circle, or diamond)

Question 7

What is digenic inheritance

Answer 7

occurs when dz is caused by variants in two different genes

ex: Rotor syndrome (causes hyperbilirubinemia)

Question 8

What is the coefficient of inbreeding for full siblings, half siblings, two first cousins

Answer 8

F: the chance of homozygosity by descent at a given locus
full sibs: 1/4
half sibs: 1/8 (you H8 your half sibs)
two first cousins: 1/16

Question 9

What is the degree of relatedness (coefficient of relationships) for identical twins, full sibs, 3/4 sibs, half siblings

Answer 9

identical twins: 1 (100% genetically related)
full sibs: 1/2
3/4 sibs: 3/8
half sibs: 1/4
To get F (coefficient of inbreeding) divide these values by 2

Question 10

Define epistaxis

Answer 10

interaction between 2 genes

Question 11

Define pleiotropy

Answer 11

plenty of traits from one copy of a gene (untx PKU –> ID, musty odor, fair skin)
exam questions about pleiotropy will refer to traits in 1 person (vs a family)

Question 12

Define microchimerism

Answer 12

seen during pregnancy (fetal cells enter maternal circulation) or after blood transfusion and organ transplants.
consider tetragametic chimerism (from fusion of non-identical embryos) when you have a pt w 2 distinct karyotypes (both 46,XX and 46,XY)

Question 13

What conditions are the result of somatic mosaicism

Answer 13

Segmental NF1
McCune Albright (GNAS)
Proteus syndrome (AKT)
PIK3CA-related overgrowth spectrum

Question 14

What is a risk allele

Answer 14

increases the risk for a condition. Generally are low penetrance (most people w the allele do not have the condition

Question 15

What is an individual w Gaucher and a carrier for Gaucher at increased risk for

Answer 15

higher likelihood or Parkinson dz in ppl dx w type 1 Gaucher dz who are older than 60; even by 80yo, risk does not exceed 80%
in the carriers of Gaucher dz, there is a higher prevalence of Parkinson dz compared w people of a comparable age who do not have Gaucher mutations

Question 16

What isolated findings are more common to one sex

Answer 16

Clubfoot (males); Cleft palate alone (females); NTD (females); hip dysplasia (males); pyloric stenosis (males)

Question 17

What is the relationship between Bayes and PPV/NPV

Answer 17

Prior (use the prevalence of the dz)
Conditional (use the sensitivity/specificity)
Joint (multiply)
Posterior (reflects PPV or NPV)

Question 18

How can you determine who is the best person to test in a family w recurrent BWS or simplex BWS

Answer 18

you need to test either a MATERNAL parent of an affected child or a MATERNAL grandfather
when the CDKN1C variant is passed through a MALE, his children will be unaffected; if passed through a FEMALE children will be affected
In the “mans” (WiedeMANn, AngelMAN) the “man’s” copy of the gene is imprinted (silenced); thus, if there is a mutation of the maternally inherited copy, this will result in the dz

MAT CDKN1C PVs are the most common cause of recurrent BWS

Question 19

What types of conditions does GINA protect and does NOT protect

Answer 19

protect: presymptomatic screening (HTT, BRCA1/2)
not protect: manifest conditions (CFTR, GBA)

Question 20

What is clonal hematopoiesis

Answer 20

results from somatic mutations in hematopoietic stem cells, which give an advantage to mutant cells, driving their clonal expansion and potentially leading to leukemia. The acquisition of these mutations occurs w normal aging. Have been detected in >10%of individuals > or= 65yrs

Question 21

When would you have to consult an ethics committee

Answer 21

disclosing incidental findings on genetic testing (non-paternity)
deviations from IRB approved research protocols (discovery of medically actionable finding in clinical research when there is no pt notification clause in the study protocol)
medical/lab errors (mistake in IVF/lab mistakenly reports secondary findings when pt opted out of these findings)
conflicts between parents and pts on tx decisions (if not life-threatening)
disagreement between mother and father on whether to proceed with genetic testing/tx for their child
end of life decisions

Question 22

Describe the process of PGT

Answer 22

Dx testing still needs to be offered during the pregnancy to confirm PGT results bc it is a SCREENING test due to the possibility of FP/FN

1. egg fertilization
2. embryos grow for several days (3-5dys
3. embryo bx: a subset of cells is removed from the embryo and submitted for genetic testing
4. the embryos are frozen while results are pending
5. embryos are selected based on genetic test results and transferred to the uterus

Question 23

What is PGT-A

Answer 23

screen embryo for missing/extra chroms
incorrect results may be due to mosaicism in the embryo
mosaic embryos not typically used for transfer since there is limited data on pregnancy outcomes UNLESS all other embryos are euploid

Question 24

What is PGT-SR? PGT-M?

Answer 24

SR: screen for unbalanced t’s or inversions when a parent is a known carrier of a balanced t or other structural chromosome change
M: screen embryo for familial variant that parent has been confirmed to carry

Question 25

How long after a nonreportable result from NIPS due to low ff should you re run it

Answer 25

at least 2 wks

Question 26

Bottleneck

Answer 26

When a population size is greatly reduced, the genetic diversity of the remaining smaller population
is limited.

Question 27

Dominant negative

Answer 27

Genetic variant that results in a
protein that interferes with the normal function of the wild-type protein and negatively affects the cell.

Question 28

Founder effect

Answer 28

Reduction in genetic diversity that
occurs when a small group is separated from a larger population. A genetic variant in this small population can become more prevalent as that population grows.

Question 29

Gene flow

Answer 29

Process where genes move from one population to another. Can occur through migration.

Question 30

Genetic drift

Answer 30

Change in allele frequencies due to
random events or chance such as individuals dying or not reproducing. Effect is strongest in small populations.

Question 31

Haploinsufficiency

Answer 31

Form of dominance. When a gene
has a deletion or loss-of-function mutation, the dosage of the gene product is not enough for typical function. Two wild type copies of a gene are required for the typical phenotype.

Question 32

Define advanced empathy

Answer 32

Counselor is making an informed guess about the patient’s experience.

Question 33

What are the 13 categories that are able to have an IEP

Answer 33

1. Specific learning disability (SLD): dyslexia
2. Speech or language impairment
3. Other heart impairment: ADHD
4. ASD
5. ID
6. Emotional disturbances
7. DD
8. Multiple disabilities
9. Hearing impairment/deafness
10. Orthopedic impairment
11. Visual impairment including blindness
12. Traumatic brain injury
13. Deaf-blindness

Question 34

What are the five assumptions that the Hardy Weinberg equilibrium makes

Answer 34

1. Random mating
2. No gene flow
3. Infinite population size
4. No selection taking place
5. No new mutations

Question 35

What is the inbreeding coefficient

Answer 35

the probability that two alleles at random location are identical and from the same ancestor
F=(1/2)^n
need to determine how many common ancestors they share and the number of people in the inbreeding path
if they share TWO common ancestors, you need to do TWO inbreeding paths and add them together to get inbreeding coefficient