Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors.
OBJECTIVE
To characterize orthologous human and murine cDNAs isolated through separate screens designed to identify genes expressed preferentially in retina.


METHODS
By screening bovine, murine, and human retinal cDNA libraries, human UNC-119 clones of two varieties and a murine cDNA clone corresponding to the most abundant human transcript were isolated. Northern blot and reverse transcription-polymerase chain reaction analyses were used to determine tissue distribution of UNC-119 expression; in situ hybridization localized it in retina to photoreceptors. Fluorescence in situ hybridization was used to map the human structural gene, and its intron- exon boundaries were elucidated by polymerase chain reaction amplification and sequencing genomic DNA.


RESULTS
UNC-119 was expressed at high levels in photoreceptors and at low levels elsewhere. The most abundant transcript encoded a protein of 240 amino 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 in humans arose from retention of the 3'-most intron, seemed to be retina-specific, and encoded a protein of 220 amino acids. The human structural gene mapped to 17q 1.2 and comprised at least five exons and four introns. A patient with neurofibromatosis type 1, which also maps to 17q11.2, and cone-rod dystrophy was examined for a deletion of UNC-119 but no abnormalities were found.


CONCLUSIONS
Given its strong degree of evolutionary conservation and abundant and nearly exclusive expression in photoreceptors, it is likely that UNC-119 plays an important role in vision and is a strong candidate gene for retinal diseases that map to 17q11.2.
Predoctoral Training Program in Human Genetics, Johns Hopkins University, Baltimore, Maryland, USA.
D A
DA
Swanson
J T
JT
Chang
P A
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Campochiaro
D J
DJ
Zack
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Valle
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002417:Cattle; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009456:Neurofibromatosis 1 / Q000235:genetics; D010786:Photoreceptor Cells / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D012162:Retinal Degeneration / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; C098176:UNC-119 protein, C elegans