Board Review Course Flashcards
What are the general instructions for pedigree development as outlined by the standard for pedigree nomenclature
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
What is the designation for stillbirth on pedigree? spontaneous abortion? ectopic pregnancy?
stillbirth: SB w GA and karyotype if known
spontaneous abortion: SAB w GA/gender if known
Ectopic: ECT
What is the difference between no children by choice or reason unknown vs infertility
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)
What is the difference on a pedigree with adoption into a family and adoption out of a family
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)
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?
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
How would you write, on a pedigree, an asymptomatic/presymptomatic carrier
line down the center of the pedigree symbol (square, circle, or diamond)
What is digenic inheritance
occurs when dz is caused by variants in two different genes
ex: Rotor syndrome (causes hyperbilirubinemia)
What is the coefficient of inbreeding for full siblings, half siblings, two first cousins
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
What is the degree of relatedness (coefficient of relationships) for identical twins, full sibs, 3/4 sibs, half siblings
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
Define epistaxis
interaction between 2 genes
Define pleiotropy
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)
Define microchimerism
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)
What conditions are the result of somatic mosaicism
Segmental NF1
McCune Albright (GNAS)
Proteus syndrome (AKT)
PIK3CA-related overgrowth spectrum
What is a risk allele
increases the risk for a condition. Generally are low penetrance (most people w the allele do not have the condition
What is an individual w Gaucher and a carrier for Gaucher at increased risk for
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
What isolated findings are more common to one sex
Clubfoot (males); Cleft palate alone (females); NTD (females); hip dysplasia (males); pyloric stenosis (males)
What is the relationship between Bayes and PPV/NPV
Prior (use the prevalence of the dz)
Conditional (use the sensitivity/specificity)
Joint (multiply)
Posterior (reflects PPV or NPV)
How can you determine who is the best person to test in a family w recurrent BWS or simplex BWS
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
What types of conditions does GINA protect and does NOT protect
protect: presymptomatic screening (HTT, BRCA1/2)
not protect: manifest conditions (CFTR, GBA)
What is clonal hematopoiesis
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
When would you have to consult an ethics committee
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
Describe the process of PGT
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
- egg fertilization
- embryos grow for several days (3-5dys
- embryo bx: a subset of cells is removed from the embryo and submitted for genetic testing
- the embryos are frozen while results are pending
- embryos are selected based on genetic test results and transferred to the uterus
What is PGT-A
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
What is PGT-SR? PGT-M?
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
How long after a nonreportable result from NIPS due to low ff should you re run it
at least 2 wks
Bottleneck
When a population size is greatly reduced, the genetic diversity of the remaining smaller population
is limited.
Dominant negative
Genetic variant that results in a
protein that interferes with the normal function of the wild-type protein and negatively affects the cell.
Founder effect
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.
Gene flow
Process where genes move from one population to another. Can occur through migration.
Genetic drift
Change in allele frequencies due to
random events or chance such as individuals dying or not reproducing. Effect is strongest in small populations.
Haploinsufficiency
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.
Define advanced empathy
Counselor is making an informed guess about the patient’s experience.
What are the 13 categories that are able to have an IEP
- Specific learning disability (SLD): dyslexia
- Speech or language impairment
- Other heart impairment: ADHD
- ASD
- ID
- Emotional disturbances
- DD
- Multiple disabilities
- Hearing impairment/deafness
- Orthopedic impairment
- Visual impairment including blindness
- Traumatic brain injury
- Deaf-blindness
What are the five assumptions that the Hardy Weinberg equilibrium makes
- Random mating
- No gene flow
- Infinite population size
- No selection taking place
- No new mutations
What is the inbreeding coefficient
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
