Title

Mutation in CEP290 Discovered for Cat Model of Human Retinal Degeneration

Authors

Marilyn Menotti-Raymond, National Cancer Institute at Frederick
Victor A. David, National Cancer Institute at Frederick
Alejandro A. Schaffer, National Institutes of Health - Bethesda
R. Stephens, National Cancer Institute at Frederick
David Wells, National Cancer Institute at Frederick
Rajendra Kumar-Singh, Tufts University
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
Kristina Narfstrom, University of Missouri - Columbia

Document Type

Article

Publication Date

5-2007

Publication Title

Journal of Heredity

ISSN

0022-1503

Volume

98

Issue/No.

3

First Page

211

Last Page

220

Abstract

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, Θ = 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.

Comments

©2007 Oxford University Press

Additional Comments

GenBank accession #: EF028068

NSUWorks Citation

Menotti-Raymond, Marilyn; Victor A. David; Alejandro A. Schaffer; R. Stephens; David Wells; Rajendra Kumar-Singh; Stephen J. O'Brien; and Kristina Narfstrom. 2007. "Mutation in CEP290 Discovered for Cat Model of Human Retinal Degeneration." Journal of Heredity 98, (3): 211-220. https://nsuworks.nova.edu/cnso_bio_facarticles/509

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015