GENOMIC STRUCTURE OF THE HUMAN GT334 (EHOC-1) GENE-MAPPING TO 21Q22.3

Several inherited diseases have been mapped to the distal tip of human chromosome 21. In our recent efforts to clone candidate genes for som e of these disorders, we have assembled a cosmid and BAC contig spanni ng 770 kb. We have identified expressed sequences from this contig by means of a cDNA hybrid selection scheme. We present here the isolation , cDNA sequence, genomic organization, and polymorphisms analysis of o ne such expressed sequence, GT334, which had been identified independe ntly and designated EHOC-1. GT334 is split into 23 exons, and spans an estimated 95 kb of genomic DNA. A pseudogene of the histone H2AZ gene has been identified, and maps within the third intron. We have identi fied an ORF potentially encoding a protein 1259 amino acids in length, longer than that described in the EHOC-1 gene. The GT334 gene was scr eened for single base pair changes using single-strand conformation po lymorphism (SSCP) analysis and we have identified seven sequence varia tions within this gene. These polymorphisms can be used as markers in the genetic mapping of other diseases localized to this region. (C) 19 97 Elsevier Science B.V.