Human cochlear expressed sequence tags provide insight into cochlear gene expression and identify candidate genes for deafness

To identify candidate genes for human hearing disorders and to understand b etter human hearing at the molecular level, we constructed a human cochlear cDNA library. An aliquot of the unsubtracted cochlear library was contribu ted to the IMAQE Consortium at Lawrence Livermore National Laboratory for t he generation of expressed sequence tags (ESTs) by the Merck/WashU EST proj ect. Over 4000 ESTs were developed from the cochlear cDNA library and depos ited in the GenBank EST database. Sequence clustering shows that the majori ty of clones are in low copy numbers, demonstrating the high complexity of the library. The sequences of 1388 cochlear ESTs (33%) match 517 known huma n genes. Among these are genes previously shown to cause both syndromic and non-syndromic hearing loss. A number of the cochlear ESTs show high homolo gy to non-human genes, suggesting new gene family members or human homologs of animal genes. We also report the chromosomal map positions of 437 cochl ear ESTs. These provide positional candidate genes for 18 different nonsynd romic hearing disorders. A Human Cochlear EST Database web site (http://www .bwh, partners.org/pathology) has been created to provide access to the coc hlear clone data for gene discovery investigations.