MAPPING OF A NOVEL HUMAN CARBONYL REDUCTASE, CBR3, AND RIBOSOMAL PSEUDOGENES TO HUMAN-CHROMOSOME 21Q22.2

To find the genes contributing to Down syndrome, we constructed a 4-Mb sequence-ready map spanning chromosome 21q22.2 with megabase-sized co smid/P1-derived artificial chromosome (PAC) contigs. The restriction m ap with rare cutting enzymes, followed by sequencing from the clusteri ng sites, has defined CpG: islands and revealed the genes associated w ith CpG islands (Accession No. D85771). Of these, two human carbonyl r eductases (CBR; EC1.1.1,184) were found in a PAC 25P16 clone. CBR cata lyzes the reduction of a large number of biologically aid pharmacologi cally active carbonyl compounds to their corresponding alcohols and ha s been mapped ill 21q22.1. To confirm these results, we sequenced the PAC clone in shotgun strategies and identified a novel carbonyl reduct ase, designated CBR3, 62 kb downstream from the original CBR, In addit ion, three ribosomal pseudogenes, L23a, S9, and L3, and some cDNAs wit h ESTs were mapped in the sequence. In conclusion, the sequence analys is for CpG islands predicted from the megabase-sized contigs will reve al and identify the genes involved in Down syndrome. (C) 1998 Academic Press.