3.6-Mb genomic and YAC physical map of the Down syndrome chromosome region on chromosome 21.

The Down syndrome chromosome region (DCR) on chromosome 21 has been shown to contain a gene(s) important in the pathogenesis of Down syndrome. We constructed a long-range restriction map of the D21S55-D21S65 region covering the proximal part of the DCR. Pulsed-field gel electrophoresis of lymphocyte DNA digested with three rare cutting enzymes. NotI, NruI, and MluI, was used to establish two physical linkage groups of 5 and 7 markers, respectively, spanning 4.6 Mb on the NotI map. Mapping analysis of 40 YACs allowed the selection of 13 YACs covering 95% of the D21S55-D21S65 region and spanning 3.6 Mb. The restriction maps of these YACs and their positioning on the genomic map allowed 19 markers to be ordered, including 4 NotI linking clones, 9 polymorphic markers, the CBR gene, and the AML1 gene. The distances between markers could also be estimated. This physical map and the location of eight NotI sites between D21S55 and D21S17 should facilitate the isolation of previously unidentified genes in this region.