The Reciprocal Hnpp Deletion

HNPP mapped to the same region as CMT1A and all 17p12 genetic markers known to be duplicated in CMT1A were shown to be deleted in HNPP (31). The HNPP deletion breakpoints

Fig. 3. Nonallelic homologous recombination (NAHR) generates the reciprocal CMT1A duplication and HNPP deletion. Schematic representation of the unequal crossover resulting from misalignment of the low-copy repeat elements, the proximal CMT1A-REP (green) and the distal CMT1A-REP (yellow) sizes of the CMT1A region and CMTlA-REPs are indicated in number of nucleotides or bases. The CMTlA-REPs share 99% of DNA sequence identity. The CMT1A-REP copies can act as substrates for homologous recombination with reciprocal crossovers (numbered 1 and 2) resulting in either the CMT1A tandem duplication or the reciprocal HNPP deletion as alternate products of NAHR.

Fig. 3. Nonallelic homologous recombination (NAHR) generates the reciprocal CMT1A duplication and HNPP deletion. Schematic representation of the unequal crossover resulting from misalignment of the low-copy repeat elements, the proximal CMT1A-REP (green) and the distal CMT1A-REP (yellow) sizes of the CMT1A region and CMTlA-REPs are indicated in number of nucleotides or bases. The CMTlA-REPs share 99% of DNA sequence identity. The CMT1A-REP copies can act as substrates for homologous recombination with reciprocal crossovers (numbered 1 and 2) resulting in either the CMT1A tandem duplication or the reciprocal HNPP deletion as alternate products of NAHR.

mapped to the same intervals as those in the CMT1A duplication. The 1.4-Mb HNPP deletion was demonstrated to be the reciprocal recombination product to the CMT1A duplication by the identification of predicted PFGE junction fragments and by showing the expected one copy of CMT1A-REP on the recombinant deleted chromosome (Fig. 3) (32,33). Thus, the HNPP deletion and CMT1A duplication represent the products of a reciprocal NAHR involving CMT1A-REP.

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