We identified four candidate retinal disease genes at four independent loci. Using the predicted translational product of these transcripts and BLAST, we compared the amino-acid sequence of these putative proteins with the public protein databases (NCBI). Of these four genes, two encode protein motifs showing homology with known proteins
(Table 3) . Clone 6 human orthologue (
Homo sapiens; AW964851) encodes for a putative protein with a central TLC homology domain containing five transmembrane α-helices (GenBank accession no. NP_113666). Overall, the predicted translation product of this gene is very well conserved in vertebrates, showing ∼94% amino-acid identity with the mouse (
Mus musculus; XP_133706) and ∼70% amino-acid identity with zebrafish (
Danio rerio; AAH59567). We also found a putative protein in
Drosophila (
Drosophila melanogaster; AF181646) that shows ∼34% identity with human NP_113666. A sequence comparison with other proteins revealed that NP_113666 possesses ∼49% identity and ∼67% similarity with CT120 and ∼28% identity and ∼50% similarity with CLN8.
CT120 encodes a membrane-associated protein that is conserved in different organisms, including plants, and it appears to be involved in amino-acid transport and glutathione metabolism.
43 CLN8 encodes a transmembrane protein and is the gene mutated in the mouse mutant motor neuron (
mnd) degeneration and in humans with the autosomal recessive disorder progressive epilepsy with mental retardation (EPMR; Mendelian Inheritance in Man [MIM] 600143).
44 These diseases are part of the neuronal ceroid lipofuscinoses, a group of neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in various tissues. Notably,
mnd mice display photoreceptors degeneration whereas another lipofuscinoses-related gene,
CLN3, is the mutated gene in Batten-disease, a degenerative disorder characterized by early-onset retinal pigmentary degeneration and later mental deterioration.
45 46 Coincidentally, the
CLN3 gene is located at 16p11.2, thus relatively close to AW964851 at 16p12.1 (http://www.sph.uth.tmc.edu/retnet/disease.htm; RetNet). The other candidate disease gene we identified and which displays homology with known genes is clone 8. Clone 8 is weakly homologous (52% of homology) to nectin-like 1 (
necl-1). Necl are a recently characterized group of proteins that share structural similarities with nectins. Nectins are a family of Ca
2+-independent immunoglobulin-like cell–cell adhesion molecules involved in the formation of cadherin-based adherens junctions.
47 In turn, Necls heterophilically interact with nectins to regulate cell polarization and migration. Thus, clone 8 could be involved in cell–cell interactions between the RPE and photoreceptors to either stabilize or organize adherens junctions.