GENE IDENTIFICATION IN 1.6-MB REGION OF THE DOWN-SYNDROME REGION ON CHROMOSOME-21

The Down syndrome (DS) region has been defined by analyses of partial trisomy 21. The 2.5-Mb region between D21S17 and ERG is reportedly res ponsible for the main features of DS. Within this 2.5-Mb region, we fo cused previously on a distal 1.6-Mb region from an analysis of Japanes e DS patients with partial trisomy 21. Previously we also performed ex on-trapping and direct cDNA library screening of a fetal brain cDNA li brary and identified a novel gene TPRD. Further screening of a fetal h eart cDNA library was performed and a total of 44 possible exons and 9 7 cDNA clones were obtained and mapped on a BamHI map. By rescreening other cDNA libraries and a RACE reaction, we isolated nearly full-leng th cDNAs of three additional genes [holocarboxylase synthetase (HCS), C protein-coupled inward rectifier potassium channel 2 (GIRK2), and a human homolog of Drosophila minibrain gene (MNB)] and a coding sequenc e of a novel inward rectifier potassium channel-like gene (IRKK). The gene distribution and direction of transcription were determined by ma pping both ends of the cDNA sequences. We found that these genes, exce pt IRKK, are expressed ubiquitously and are relatively large, extendin g from 100 kb to 300 kb on the genome. These nearly full-length cDNA s equences should facilitate understanding of the detailed genome struct ure of the DS region and help to elucidate their role in the etiology of DS.