A TRANSCRIPT MAP OF THE DOWN-SYNDROME CRITICAL REGION ON CHROMOSOME-21

A catalogue of the genes encoded by chromosome 21 would provide a fram ework for assigning roles in the etiology of Down syndrome (DS) to ind ividual genes. We have begun generating such a catalogue, starting wit h a 1.2 Mb region surrounding the marker D21S55. Our efforts utilized the yeast artificial chromosome (YAC) and cosmid-clone based high reso lution physical maps that we have constructed of this region. Direct-s election of fetal brain cDNAs with YAC DNA was used to isolate transcr ibed sequences. The selected cDNA fragments were analyzed by limited D NA sequence analysis, Northern blot hybridization and screening of cDN A libraries. The cDNA fragments were assigned positions on the physica l map by hybridization to a collection of cosmid clones. The accurate determination of map positions for individual cDNA fragments allowed u s to determine sources of variability in the cDNA selection procedure. The combined analysis and mapping was used to estimate the completene ss of our mapping efforts and to identify procedures that would facili tate large-scale transcript mapping. The transcribed sequence map that we have assembled will allow the importance to DS of genes in this re gion to be examined and will aid in the design of strategies for large r scale efforts.