General Info - Test 1

Question 1

Alternate segregation

Answer 1

Quadrivalent crisscross: catty corner chromosomes go together to same cell
-Result: one normal cell, one balanced translocation cell

Question 2

Adjacent I segregation

Answer 2

Quadrivalent horizontal sets: pulls one of each centromere type ( i.e. different homologs)  all offspring unbalanced, usually smaller unbalance than Adj II b/c did pull different homologs

Question 3

Adjacent II segregation

Answer 3

quadrivalent vertical sets go together: pulls same centromeres together (i.e. “same” homologs)  all offspring unbalanced, usually bigger unbalance than Adj I b/c pulled same homologs

Question 4

3:1 segregation Option 1

Answer 4

• take two normal chromosomes and one odd, other odd goes the other way
• Result: tertiary trisomy or tertiary monosomy

Question 5

3:1 segregation Option 2

Answer 5

• Take both odd chromosomes and one normal, other normal goes the other way
• Result: interchange trisomy or interchange monosomy

Question 6

Tertiary trisomy

Answer 6

• Normal chrom A, normal chrom B, odd with parts of A and B –> when add partner chromosomes: will be trisomic for the parts of A and B on odd chromosome

Question 7

Tertiary monosomy

Answer 7

Odd with parts of A and B –> when add partners A and B: monosomic for the parts of A and B missing from the odd chromosome

Question 8

Interchange trisomy

Answer 8

have one normal A, odd A/B, complement odd A/B, –> when add partner’s normal A and B have overall complete additional A (Trisomy A) and the odd chroms Bs complement so no other probs

Question 9

Balanced Translocation Microarray

Answer 9

terminal dup and del on DIFFERENT chromosomes

Question 10

Pericentric inversion

Answer 10

• include centromeres (breakpoints in both arms)
• Leads to: meiosis 1 segregation and recombination errors (loop forms, and cross over leads to deletions and duplications)
• Risk of inversion carrier having unbalanced viable offspring Is 5-10%

Question 11

Paracentric inversion

Answer 11

• does NOT include centromere (breakpoints in one arm)
  -Leads to: Meiosis 1 segregation and recombination errors:
  -Classic loop crossover: one dicentric with dup and del, one acentric with dup and del (lost)
  -U-loop exchange: monocentric chromosome with inverted dup, monocentric chromosome with deletion
  -Risk of inversion carrier having unbalanced viable offspring: 0.1-0.5%

Question 12

Pericentric Inversion on microarray

Answer 12

(only showing unbalanced offspring) Terminal deletion and terminal duplication on SAME chromosome

Question 13

Ring chromosomes

Answer 13

o Common clinical features:
 Growth restriction
 Mild-mod ID
 Minor dysmorphic features
 Infertility
o On CMA: both ends of one chromosome are deleted

Question 14

Isochromosomes

Answer 14

Chromatids break apart incorrectly (vertically): 2 p arms together, 2 q arms together
o CMA: Non-supernumerary: trisomy of one arm, monosomy of other
 Supernumerary: tetrasomy of p or q arm
o Examples:
 Isochromosome Xq (variant of Turner syndrome)
 Pallister-Killian Syndrome (mosaic tetrasomy 12p)

Question 15

Do novo structural arrangements most common origin

Answer 15

Meiosis I, sperm

Question 16

Non-Allelic Homologous Recombination (NAHR)

Answer 16

Mediated by segmental duplications dispersed between genes –> can line up inappropriately leading to dups/dels/inversions
 Most common cause of recurrent structural variants

Question 17

Non-Homologous End Joining

Answer 17

 Double strand break (repeats break easily): machinery looks for another broken end –> chews back both until finds overhand that can be stuck together –> stick them together (emergency measure)
 Have breakpoint scaring (do to del/dup at ends)
 Most common cause for nonrecurrent structural variants (translocations, inversions)

Question 18

Common Robertsonian Translocations

Answer 18

-Der(13;14): Most common structural chromosome rearrangement
(Increased prevalence in infertile men)
-Der(14;15)
-Der(15;15)
-Der(13;14

Question 19

Mike Bertram, Murray Barr

Answer 19

Discovered the barr body (inactive X)

Question 20

Mary Lyon and Liane Russel

Answer 20

Lyon Hypothesis: X-inactivation

Question 21

Ultrasound Signs of Aneuploidy

Answer 21

-Nuchal translucency (big in Turner)
-Absent nasal bone (T21)
-Renal malformations (T21, Turner)
-Brain malformations (T13, T18)
-Clefting (T13)
-Clubfoot (T13, T18)
-Omphalocele (T18)

Question 22

Screening Tests

Answer 22

maternal serum, NIPT (placental cell free DNA), US

Question 23

Diagnostic tests

Answer 23

CVS, amniocentesis

Question 24

Maternal Serum Testing

Answer 24

o Timing: can do some in first-trimester, full in second trimester
o What is tested: levels of hCG, Alpha-fetoprotein, etc.  bell curves of normal can show if outside of normal = higher risk of problem
o What can be detected: higher risk for the common genetic conditions:
 Down Syndrome: high hCG, low in others
 T18: low for everything
 NTD: high in AFP
o Pros/cons:
 Non-invasive
 Can be done early
 Shows risks
 Cons: not diagnostic, only see most common genetic conditions, screening can be confusing in results

Question 25

NIPT

Answer 25

o Timing: >10 weeks
o What is tested: DNA that is from placenta in mother’s blood
o What can be detected: common genetic conditions:
 Down Syndrome (good predictive value)
 T18 (good predictive value)
 T13 (lower predictive value)
 Sex chromosome aneuploidies (decent predictive values)
 Triploidy (lower predictive value)
 Note: predictive value better if mother AMA
o No Calls and discordant results:
 Resorbed twins
 Confined placental mosaicism
 Cancer
 Obesity in mother
 Vit B12 Deficiency
 Triplets
 Twin demise
 Anueploidy can throw off less DNA
o Pros/cons:
 Non invasive
 Looking at DNA (not just hormones) so can detect a few more common genetic conditions
 Cons: looking at placental DNA, not diagnostic

Question 26

CVS

Answer 26

o Timing: 11 wks to 13 wks 6 days
o What is tested: placenta
o What can be detected: can do FISH, CMA, karyotype: diagnose a lot of things (but remember PLACENTAL)
o Pros/cons:
 More diagnostic
 Can be done earlier than amnio
 Cons: placental DNA might be different than fetus, risk of miscarriage, higher risk for maternal DNA contamination

Question 27

Amniocentesis

Answer 27

o Timing: 16+ weeks
o What is tested: fetal DNA in amniotic fluid
o What can be detected: can do FISH, CMA, karyotype
o Pros/cons:
 Diagnostic
 Looking directly at fetal DNA
 Cons: Risk of miscarriage, must be done later (16+ weeks)