Journal of Heredity Advance Access published online on May 16, 2007
Journal of Heredity, doi:10.1093/jhered/esm019
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Published by Oxford University Press 2007.
Mutation in CEP290 Discovered for Cat Model of Human Retinal Degeneration
From the Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, MD 21702 (Menotti-Raymond, David, Wells, O'Brien); National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20894 (Schäffer); Advanced Biomedical Computing Center, National Cancer Institute-Frederick, Frederick, MD 21702 (Stephens); Department of Ophthalmology, Tufts University School of Medicine, Boston, MA 02111 (Kumar-Singh); and Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Columbia, MO 65211 (Narfström); and Department of Ophthalmology, Mason Eye Institute, University of Missouri-Columbia, Columbia, MO 65211 (Narfström)
Address correspondence to M. Menotti-Raymond at the address above, or e-mail: raymond{at}ncifcrf.gov.
A mutation in the CEP290 gene is reported in a cat pedigree segregating for autosomal recessive (AR) late-onset photoreceptor degeneration (rdAc). An initial screen of 39 candidate genes and genomic locations failed to detect linkage to cat rdAc. Linkage was ultimately established on cat B4 with 15 simple tandem repeat markers (logarithm of odds [LOD] range 4.83–15.53, 
= 0.0), in a region demonstrating conserved synteny to human chromosome 12, 84.9–90.63 Mb. The sequence of 10 genes with feline retinal expression was examined in affected and unaffected individuals. A single-nucleotide polymorphism was characterized in intron 50 of CEP290 (IVS50 + 9T>G) that creates a strong canonical splice donor site, resulting in a 4-bp insertion and frameshift in the mRNA transcript, with subsequent introduction of a stop codon and premature truncation of the protein. A population genetic survey of 136 cats demonstrated that the rdAc mutation is in low frequency in Abyssinian populations (0.13, Sweden; 0.07, United States) and absent in breeds of non-Abyssinian heritage. Mutations in CEP290 have recently been shown to cause two human diseases, Joubert syndrome, a syndromic retinal degeneration, and Leber's congenital amaurosis, an AR early-onset retinal dystrophy. Human AR retinitis pigmentosa is among the most common causes of retinal degeneration and blindness, with no therapeutic intervention available. This identification of a large animal model for human retinal blindness offers considerable promise in developing gene-based therapies.
Corresponding Editor: Roger Reeves
Received March 3, 2007
Accepted March 19, 2007
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