Isolation of a marker linked to the Charcot-Marie-Tooth disease type IA gene by differential Alu-PCR of human chromosome 17-retaining hybrids.

We report the isolation of a new marker (S6.1) from band p11.2 of human chromosome 17 by differential Alu-polymerase chain reaction (Alu-PCR) of both a monochromosomal hybrid retaining a single human chromosome 17 and a hybrid retaining a del(17)(p11.2p11.2) in addition to other human chromosomes. The method is based on the preferential PCR amplification of human DNA in rodent/human hybrids when primers specific to the human Alu repeat element are used. MspI and SstI RFLPs associated with S6.1 were identified and used in linkage analysis of both a previously reported and a newly identified French-Acadian kindred segregating autosomal dominant Charcot-Marie-Tooth disease (CMT). A cumulative peak lod score of 3.41 at a peak recombination fraction of .12 indicates that this marker is linked to the CMT 1A locus but is at a distance from the disease gene. Thus, the marker S6.1 will be useful in further delineating the candidate region for the CMT gene when its location with respect to pA10-41 and 1516, two other markers from 17p11.2 which have previously demonstrated close linkage to the CMT locus, has been determined.