The Principles of Clinical Cytogenetics - Extra Materials - Springer

182 Kathleen Kaiser-Rogers and Kathleen Rao
Fig. 11. Left: A normal 16, an inverted chromosome 16, and a recombinant chromosome 16 [rec(16)dup(16q)
inv(16)(p13.3q23)] resulting from recombination within the inversion loop of the parental inversion carrier.
The recombinant chromosome 16 is missing the material distal to the short arm breakpoint and contains a
duplication of the material distal to the breakpoint within the long arm. Right: A metaphase that has been
hybridized with a FISH probe specific for the subtelomeric region in the long arm of chromosome 16. A signal
is seen on the distal long arm of the normal chromosome 16 (small arrow) and on both arms of the recombinant
chromosome 16 (large arrow), confirming the duplication of long arm material.
inverted segment forms a loop that can then pair with homologous regions on the normal chromosome.
The noninverted portions of the chromosome (the chromosome segments distal to the inversion
breakpoints) pair linearly with homologous regions on the normal chromosome. An odd number
of crossovers between the same two chromatids within the inversion loop will result in the production
of recombinant chromosomes, whereas an even number of crossovers between the same two chromatids
within the inversion loop should result in the production of normal or balanced chromosomes.
Two types of recombinant chromosome are formed when crossing-over occurs between the inversion
breakpoints. One recombinant will contain a duplication of the material distal to the breakpoint
on the short arm and a deletion of the material distal to the breakpoint in the long arm. The second
recombinant is complementary to the first and contains a short arm deletion and a long arm duplication
(Figs. 10 and 11). Both recombinants are known as duplication-deficiency chromosomes.
Alternate models for pairing in an inversion heterozygote are seen in Figs. 10B,C. In inversions
with very small inverted segments (breakpoints are close to the centromere and the distal segments
are large), the noninverted segments of both chromosomes could pair in linear fashion, with asynapsis
or failure to pair in the small inverted segment. In this model, crossing-over can only take place in
the noninverted segments of the chromosomes, and thus abnormal recombinant chromosomes are not
formed. In the opposite situation, where the inverted segment is very large relative to the size of the
entire chromosome and the distal segments are small, pairing could occur only between the inversion
breakpoints and the distal material will remain unpaired. In this situation, a crossover between the inversion
breakpoints would produce recombinant chromosomes in a manner similar to the reverse loop
model discussed previously. Crossing-over could not take place in the segments distal to the inversion
breakpoints because those regions do not pair.
Careful examination of the recombinant chromosomes produced when crossing-over takes place
between the breakpoints in a pericentric inversion reveals that the genetic imbalance always involves
the material distal to the inversion breakpoints. Thus, large inversions have small distal segments and
produce recombinant chromosomes with small duplications and deficiencies, whereas small inversions
have large distal segments and produce recombinant chromosomes with large duplications and