The Principles of Clinical Cytogenetics - Extra Materials - Springer

166 Kathleen Kaiser-Rogers and Kathleen Rao
Fig. 1. Chromosome rearrangements can be produced by nonallelic homologous recombination between
shared sequences or repeats of identical (direct repeats) or opposite (inverted repeats) orientation. Recombination
between direct, nonallelic repeats on homologous chromosomes (A) or sister chromatids (B) can produce
complementary duplications and deletions. Recombination between direct repeats located at different sites
within a single chromatid can produce both deletions and acentric ring chromosomes (C). If, instead, recombination
occurs between inverted repeats within a single chromatid, a chromosome inversion is produced (D).
Translocations and other more complex rearrangements can occur secondary to recombination events between
shared sequences that are located on different chromosomes (E). Shared sequences or repeats are designated by
arrows, and the lowercase letters represent unique sequences.
events appear to reflect the location, size, and orientation of the LCRs, as well as the number of
crossover events that occur within the LCR.
Direct LCRs (those with the same orientation) located on the same chromosome can mediate both
duplications and deletions as shown in Fig. 1. When a single, nonallelic, homologous recombination
event involving homologous chromosomes (interchromosomal) or sister chromatids (intrachromosomal)
is mediated by direct LCRs, complementary duplications and deletions occur (see Figs. 1A,B).
Only deletions are predicted to occur, however, if nonallelic homologous recombination involving
direct LCRs occurs within a single chromatid (intrachromatid; Fig. 1C). As shown in Fig. 1D, inversions
can form secondary to intrachromatid recombination events within a pair of nonallelic homologous
inverted LCRs. Nonallelic recombination events involving LCRs located on completely different
chromosomes would be expected to produce translocations (see Fig. 1E) as well as other more complex
rearrangements (7).
The size of the inversions, duplications, and deletions produced by the recombination events
described above are dependent on the length and proximity of the LCRs mediating the rearrangement.
In general, the larger the rearranged region, the larger the LCR that mediates the recombination
event. Single-gene rearrangements occur when the recombining homologous sequences flank or are
within a single gene. These rearrangements are submicroscopic, require molecular techniques for
their identification, and typically result in Mendelian genetic disorders such as Charcot–Marie–Tooth
disease type 1A, hereditary neuropathy with liability to pressure palsies (HNPP), hemophilia A, and
many others (6). In contrast to single-gene rearrangements, recombination events that utilize nonal-