MAPPING OF THE HUMAN HOLOCARBOXYLASE SYNTHETASE GENE (HCS) TO THE DOWN-SYNDROME CRITICAL REGION OF CHROMOSOME 21Q22

Exon trapping/amplification was used to clone portions of genes from t he Down syndrome critical region (DSCR) of human chromosome 21q22, Two trapped sequences showed complete homology with nucleotide sequence D 23672 of genbank which corresponds to the gene for the human holocarbo xylase synthetase (HCS) that was previously assigned to chromosome 21, We precisely mapped this gene to the DSCR by somatic cell hybrids, ch romosome 21-specific YACs, and hybridization to chromosome 21-specific cosmids; it localizes to YACs 745H11 and 230E8 of the Chumakov et al, (Nature 359:380, 1992) YAC contig in a region of less that one megaba se between markers D21S333 and D21S267, This HCS gene may contribute i n a gene dosage-dependent manner to the phenotype of Down syndrome.