Increased Recombination Adjacent to the Huntington

Huntington disease (HD) is caused by a genetic defect dis-tal to the anonymous DNA marker D4SlO in the terminal cytogenetic subband of the short arm of chromosome 4 (4~16.3). The effort to identify new markers linked to HD has concentrated on the use of somatic cell hybrid panels that split 4~16.3 into proximal and distal portions. Here we report two new polymorphic markers in the proximal por-tion of 4~16.3, distal to D4SlO. Both loci, D4S126 and D4Sl27, are defined by cosmids isolated from a library enriched for sequences in the 4pter-4p15.1 region. Physi-cal mapping by pulsed-field gel electrophoresis places D4S126 200 kb telomeric to D4SI0, while D4S127 is lo-cated near the more distal marker D4S95. Typing of a ref-erence pedigree for D4S126 and 049127 and for the re-cently described VNTR marker D4S125 has firmly place