Winn Grant Report
W12-022: Molecular characterization of Bengal progressive retinal atrophy; $4,221, Dr. Robert Grahn, University of California, Davis
Inherited blindness is a devastating disease common to many mammalian species. In people, over 25 different forms of inherited retinal blindness have been clinically characterized. Cats also have several forms of blindness that destroy the photoreceptors at the back of the eye. These conditions will randomly occur in a particular cat breed and then will be inherited. Some forms of blindness attack the photoreceptors shortly after birth, while other forms take longer to destroy the layer of the eye responsible for vision.
Several Bengal cats have been diagnosed with a form of blindness that destroys their vision around five months of age. A genome wide case control association study has indicated a candidate region for Bengal progressive retinal atrophy (PRA).
The objective of this study was to sequence a candidate gene found in the genomic region linked to the disease. The candidate gene, FAM161A, has been demonstrated to cause progressive retinal atrophy in people. The goals were to sequence both the RNA copy of the gene, and if no variants were found, to sequence the noncoding regions of the gene to detect potential splice variants.
FAM161A RNA isolated from the retinas of affected and unaffected cats were completely sequenced. No differences were detected between the two transcripts. The 5’ untranslated as well as some intronic data were generated. Differences in the noncoding region of the gene were found. Affected cats are homozygous and distinct from the control cats. However, this difference did not segregate with the disease; thus, FAM161A was effectively eliminated as a candidate gene.
Additional cats were added to the association study and a new, refined linkage region was identified. A gene related to feline PRA (CEP290 in Abyssinians) is located within this new linkage region. Genome sequencing is being pursued by the investigators to determine if this is a marker for the condition in Bengal cats. [MK]
Rah H, Maggs DJ, Blankenship TN, et al. Early-onset, autosomal recessive, progressive retinal atrophy in Persian cats. Invest Ophthalmol Vis Sci 2005;46:1742-1747. [free, full text]