General Info - Test 1 Flashcards
Alternate segregation
Quadrivalent crisscross: catty corner chromosomes go together to same cell
-Result: one normal cell, one balanced translocation cell
Adjacent I segregation
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
Adjacent II segregation
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
3:1 segregation Option 1
- take two normal chromosomes and one odd, other odd goes the other way
- Result: tertiary trisomy or tertiary monosomy
3:1 segregation Option 2
- Take both odd chromosomes and one normal, other normal goes the other way
- Result: interchange trisomy or interchange monosomy
Tertiary trisomy
- 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
Tertiary monosomy
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
Interchange trisomy
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
Balanced Translocation Microarray
terminal dup and del on DIFFERENT chromosomes
Pericentric inversion
- 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%
Paracentric inversion
- 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%
Pericentric Inversion on microarray
(only showing unbalanced offspring) Terminal deletion and terminal duplication on SAME chromosome
Ring chromosomes
o Common clinical features:
Growth restriction
Mild-mod ID
Minor dysmorphic features
Infertility
o On CMA: both ends of one chromosome are deleted
Isochromosomes
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)
Do novo structural arrangements most common origin
Meiosis I, sperm
Non-Allelic Homologous Recombination (NAHR)
Mediated by segmental duplications dispersed between genes –> can line up inappropriately leading to dups/dels/inversions
Most common cause of recurrent structural variants
Non-Homologous End Joining
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)
Common Robertsonian Translocations
-Der(13;14): Most common structural chromosome rearrangement
(Increased prevalence in infertile men)
-Der(14;15)
-Der(15;15)
-Der(13;14
Mike Bertram, Murray Barr
Discovered the barr body (inactive X)
Mary Lyon and Liane Russel
Lyon Hypothesis: X-inactivation
Ultrasound Signs of Aneuploidy
-Nuchal translucency (big in Turner)
-Absent nasal bone (T21)
-Renal malformations (T21, Turner)
-Brain malformations (T13, T18)
-Clefting (T13)
-Clubfoot (T13, T18)
-Omphalocele (T18)
Screening Tests
maternal serum, NIPT (placental cell free DNA), US
Diagnostic tests
CVS, amniocentesis
Maternal Serum Testing
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
NIPT
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
CVS
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
Amniocentesis
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)
