MAMMALIAN ORTHOLOGS OF C-ELEGANS UNC-119 HIGHLY EXPRESSED IN PHOTORECEPTORS

PURPOSE. TO characterize orthologous human and murine cDNAs isolated t hrough separate screens designed to identify genes expressed preferent ially in retina.METHODS. By screening bovine, murine, and human retina l cDNA Libraries, human UNC-119 clones of two varieties and a murine c DNA clone corresponding to the most abundant human transcript were iso lated. Northern blot and reverse transcription-polymerase chain reacti on analyses were used to determine tissue distribution of UNC-119 expr ession; in situ hybridization localized it in retina to photoreceptors . Fluorescence in situ hybridization was used to map the human structu ral gene, and its intron- exon boundaries were elucidated by polymeras e chain reaction amplification and sequencing genomic DNA. RESULTS. UN C-119 was expressed at high levels in photoreceptors and at low levels elsewhere. The most abundant transcript encoded a protein of 240 amin o acids with homology to Caenorhabditis elegans UNC-119. Rat and human cDNAs of UNC-119 have been previously reported as human retinal gene 4 and rat retinal gene 4 (HRG4 and RRG4). An alternative splice form i n humans arose from retention of the S'-most intron, seemed to be reti na-specific, and encoded a protein of 220 amino acids. The human struc tural gene mapped to 17q11.2 and comprised at least five exons and fou r introns. A patient with neurofibromatosis type 1, which also maps to 17q11.2, and cone-rod dystrophy was examined for a deletion of UNC-11 9 but no abnormalities were found. CONCLUSIONS. Given its strong degre e of evolutionary conservation and abundant and nearly exclusive expre ssion in photoreceptors, it is likely that UNC-119 plays an important role in vision and is a strong candidate gene for retinal diseases th; it map to 17q11.2.