Structural Rearrangements Flashcards
Percent of structural abnormalities in patients with ID or autism
15-20%
Incidence of structural abnormalities (livebirths and conceptions)
1:400 livebirths, 1:200 conceptions
Structural abnormalities more likely to occur in maternal or paternal meiosis
paternal
Interstitial deletions percent
84% paternal
Terminal deletions percent
70% paternal
Duplications percent
58% paternal
Translocations percent
62% paternal
Reciprocal translocations percent
96% paternal
Robertsonian translocations are mostly maternal or paternal in origin
maternal
Recurrence risk for numerical abnormalities
1% in mid 30s
Recurrence risk for structural abnormalities
1-50%
Incidence of robertsonian translocation
1:1,000
Acrocentric chromosomes
13, 14, 15, 21, 22
Most common robertsonian translocation and percent
13;14 75-85%
Second most common type of robertsonian translocation and percent
14:21 8-10%
least common type of robertsonian translocation and what type of inheritance event
homologous and de novo
21;21 rob translocation is what risk
100%
Reciprocal translocation incidence
1:700-1:1000
Reciprocal translocation
exchange of genetic material between non-homologous chromosomes or at non-homologous sites
Percent of balanced reciprocal translocations that are inherited
70%
If reciprocal translocation is inherited, what is the risk
no increased risk
If reciprocal translocation is de novo, risk is
6-7%
Percent of reciprocal translocations that are de novo
30%
small distal segments lead to
small imbalances and large risks for clinically affected live born children
Large distal segments lead to
large imbalances and low risks for having live born abnormal children (high risks for miscarriages and period of infertility)
Partial trisomies compatiable with life
8, 9, 13, 18, 21, x, y
Partial monosomies that are compatible with life
4p, 5p, x, y
Empiric risk of unbalanced liveborn child with previous child with unbalance
20-25%
Empiric risk of unbalanced liveborn child with multiple miscarriages and no liveborn unbalanced individuals
2-4%
Empiric risk of unbalanced liveborn child who was accidentally ascertained (ex: through amnio)
4-5%
Factors that help drive reproductive risk for translocation
mode of ascertainment, size of exchanged segment, and chromosome regions involved
Inversions
two-break intrachromosomal rearrangement in which material flips over or reverses orientation
Percent of inversions that are inherited
80-90%
Pericentric inversions
centromere is included between the two breakpoints
Paracentric inversion
centromere is not between two breakpoints
Duplication-deficiency recombinant chromosomes
odd number of crossovers that leads to loss of material
Normal recombinant chromosomes
even number of crossovers, no net gain or loss of material
The larger the inversion
higher risk for live born abnormal child
- have small distal segments, which produce small imbalances
- farther apart the breakpoints, the more likely crossovers will occur between them and form recombinant duplication/deficiency chromosomes
Small inversions
less likely to be associated with live born abnormal child
Empiric risk of pericentric inversion through abnormal child
5-15%
Empiric risk of pericentric inversion if ascertained fortuitously through prenatal diagnosis
1%
Types of chromosomes formed from paracentric inversions
dicentric and acentric
Empiric risk of unbalanced offspring with paracentric inversion is
.1-.5%
Insertions
3 break rearrangements where a piece of chromosomal material is excised from one location and inserted at a new location
Incidence of insertions
1:80,000-1:10,000
Intrachromosomal insertions
all 3 breaks within the same chromosome
Interchromsomal insertions
break points in different chromosomes
Empiric risk of intrachromosomal insertion in abnormal child
50%
Empiric risk of interchromosomal insertion abnormal child
32-36%
Ring chromosome
when a chromosome undergoes 2 breaks and the broken ends reunite in ring structure
result from a ring chromosome that replaces normal chromosome
partial monosomy
Result of a supernumerary ring chromosome
partial trisomy
How are ring chromosome usually passed down
de novo
incidence of ring chromosomes
1:27,225
Most common ring chromosomes
13 and 18
Typical phenotype of ring syndrome
severe growth restriction without major malformations, mild-moderate ID, minor anomalies
Ring chromosomes are _________ during mitosis
unstable
Dynamic mosaicism seen more commonly in what kind of rings
larger
Percent of non-supernumerary rings that are inherited and by who
1% and mother
Empiric risk of transmission of ring chromosome
40%
Number of ring chromosome cases with severe phenotype
1:3
Probability that parent is balanced carrier when child is balanced carrier Trisomy 21
50-60%
Reproductive risk for balanced carriers of Trisomy 21
unbalanced offspring, miscarriages, UPD
How do balanced translocation chromosomes pair during meiosis and types
quadrivalent formation in meiosis, alternate, adjacent 1, adjacent 2
alternate 2:2 segregation forms
balanced offspring
adjacent 1 segregation
second most likely type of segregation
Adjacent 2 segregation is typically
lethal
Inverted homologues form
inversion loops during meiosis I
Offspring of parents who have recombinant imbalanced chromosomes are more likely to inherit what type of structural rearrangement
a balanced inversion
Which of the following statements are true about rings
Rings are responsible for dynamic mosaicism which can cause variation in skin
pigmentation and growth reduction.
A mother with a 46, XX karyotype and a father with a 45, XY, rob(14;21)(q10;10) karyotype plan to have a child together. They are worried about having a child with Down Syndrome. Which of the following gametes produced from the father would the child not have Trisomy 21 but still be a carrier for a Robertsonian translocation after fertilization, given that the mother gives a gamete with an independent chromosome 14 and an independent chromosome 21
A gamete with a derivative 14, 21 chromosome only
Which of the following situations could not produce a gamete that could lead to a child with a partial or full trisomy
anaphase lag
