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 sh own to contain a gene(s) important in the pathogenesis of Down syndrom e. We constructed a long-range restriction map of the D21S55-D21S65 re gion covering the proximal part of the DCR. Pulsed-field gel electroph oresis of lymphocyte DNA digested with three rare cutting enzymes, Not I, NruI, and MluI, was used to establish two physical linkage groups o f 5 and 7 markers, respectively, spanning 4.6 Mb on the NotI map. Mapp ing 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 mark ers to be ordered, including 4 NotI linking clones, 9 polymorphic mark ers, the CBR gene, and the AML1 gene. The distances between markers co uld also be estimated. This physical map and the location of eight Not I sites between D21S55 and D21S17 should facilitate the isolation of p reviously unidentified genes in this region. (C) 1994 Academic Press, Inc.