Autosomal Reciprocal Translocations
What is the prevalence rate for autosomal reciprocal translocations (ART)?
1:500
What is the prenatal risk for a ART carrier?
They have a risk of having a child with many congenital anomalies due to the inheritance of unbalanced gametes.
What is an example of a translocation associated with cancer?
chromosome 3 alteration and renal cell carcinoma.
What are the possible outcomes of 4:0 segregation?
double trisomy or double monosomy, never viable.
How is risk determined for translocation carriers?
risk must be determined individually, concerning the specific translocation and the size of segments involved.
What is a quadrivalent?
the formation of 4 chromosomes that occurs during meiosis, where common segments come together to form a cross shape that matches homologs.
t(9;21)(q12;q11) is a common example of adjacent-2 segregation. What would the possible outcomes be, and which would be viable/not viable?
the least imbalanced gamete would have the normal 9 and the der(9), where the conceptus will be dup9 and del21p. 9p is small in trisomic state, and monosomy 21p has no phenotypic effect. trisomy 9p is a known viable aneuploidy. the gamete with the der(21) causes monosomy 9p which is not viable.
What is 2:2 alternate segregation?
when one centromere goes to one pole and the next centromere goes to the other pole. only segregation that leads to complete and balanced offspring.
When does a single segment exchange occur?
when one of the translocated segments is very small and compromises only the telomeric region.
What is the risk at amnio for a unbalanced translocation carrier after a recurrent miscarriage?
about 5%
What formation would a subtelomeric translocation form, rather than a quadrivalent?
bivalent
What are the two types of 3:1 segregation?
tertiary and interchange
What is adjacent-1 segregation?
when unlike centromeres travel together. this is the most common form of mal-segregation.
What can lead to the predication of 3:1 segregation?
a lopsided quadrivalent resulting from involvement of 13, 18, and 21 chromosomes.
What is the basic population's risk for spontaneous abortion?
about 15%
What is the risk for spontaneous abortion for a balanced translocation carrier?
about 20-30%
What is the risk at amnio for a unbalanced translocation carrier if they had a previous abnormal child?
about 25%
What is the most frequent mode of segregation in reciprocal translocations?
alternate
Why is prenatal diagnosis risk for a translocation higher than at birth?
because there is a different survival rate in pregnancy due to the chance of a spontaneous abortion.
What are the portions of the derivative chromosome that are not involved in the translocation?
centric segments
What is the derivative chromosome?
der, is the rearranged chromosome that is defined by its centromere.
Where do the breakpoints most commonly occur in adjacent-2 segregation?
in the upper arm of one chromosome and right below the centromere in the other.
What must occur if a balanced translocation occurs post zygotically?
50 metaphase cells must be counted in the child to rule out mosaicism.
Do most balanced translocations occur in non-mosaic or mosaic state?
non-mosaic
What is an unbalanced translocation?
when only one of the der chromosomes is inherited by the child.
What can lead to the predication of adjacent-2 segregation?
when the centric segments are small.
What is the % range for translocation carrier risk?
0-30%
What number of chromosomes leads to the only viable outcome of 3:1 segregation?
47 chromosomes, 45 only seen in PGD.
What is the most common human reciprocal translocation in the population? (hint; it results from tertiary 3:1 segregation)
47,+der,der(22)t(11;22)(q23;q11)
What are the possible outcomes of 3:1 tertiary segregation?
either trisomy or monosomy depending on the combined content of the der chromosomes. trisomy gamete has 2 normal and one der, while monosomy has one der.
What are the possible outcomes of 3:1 interchange segregation?
full autosomal trisomy or full monosomy. trisomy would have 2 ders and one normal, while monosomy would have one normal.
What is usually the only viable conceptus involving adjacent-1?
single segment imbalances.
What are the 4 factors that determine the magnitude of risk for translocation carriers?
1) mode of ascertainment 2) predicted type to determine potential viable gametes 3) sex of transmitting parent 4) assessment of imbalance (size of segments).
What are the three modes of segregation?
2:2, 3:1, and 4:0
What are the carrier percentages for mothers and father with reciprocal translocations?
61% mothers and 39% fathers.
Why are males less frequently the translocation carrier?
Infertility resulting from nonviable sperm.
What is 2:2 adjacent segregation?
when adjacent centromeres travel together. there are two types; adjacent-1 and adjacent-2.
What can lead to the predication of 4:0 segregation?
when all chromosomes involved are large.
When does a double segment exchange occur?
when both translocated segments are large.
What is adjacent-2 segregation?
when like centromeres travel together. this is uncommon and resembles nondisjunction.
What types of chromosomes does adjacent-2 segregation involve?
most commonly involve p arms of 9 and D/G chromosomes. whole short arms are viable in a trisomic state.
What is the risk for a parent who is a balanced translocation carrier at amnio?
no increased risk for phenotypic abnormalities. could result from cryptic imbalances, position effect, or a non chromosomal cause.
Why is there a risk for cancer in rare, familial translocations?
the rearrangement may promote map-segregation and disrupt tumor suppressor gene. observed in 5q, 11q, and 17q.
What can lead to the predication of adjacent-1 segregation?
when the translocated segments are small.
