The approx 3.0-Mb CMT1A duplication, consisting of two tandem 1.4-Mb copies, results from NAHR, whereby the proximal CMT1A-REP and distal CMT1A-REP, that are separated by 1.4 Mb of genomic DNA (27), recombine resulting in a duplication (Fig. 3). This mechanism was supported by genetic evidence that showed the de novo duplication was accompanied by unequal crossover of flanking markers (3). Interestingly, as anticipated, the duplication chromosome has three copies of CMT1A-REP (20) (Fig. 1). Moreover, the CMT1A duplication was shown to be a tandem or direct duplication, and not inverted, by both PFGE and FISH (20,30). The mechanism of NAHR using flanking CMT1A-REP repeats as substrates for recombination predicted the existence of a reciprocal recombination product that would result in a deletion of the same genomic region that is duplicated in the CMT1A duplication (20).
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