Faculty Collaboration Database

Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet 2002 Aug 01;11(16):1823-33

Date

07/26/2002

Pubmed ID

12140185

DOI

10.1093/hmg/11.16.1823

Scopus ID

2-s2.0-0036667730 (requires institutional sign-in at Scopus site)   164 Citations

Abstract

Cone degeneration (cd ) is an autosomal recessive canine disease that occurs naturally in the Alaskan Malamute and German Shorthaired Pointer breeds. It is phenotypically similar to human achromatopsia, a heterogeneous autosomal recessive disorder associated with three distinct loci. Both the canine disease and its human counterparts are characterized by day-blindness and absence of retinal cone function in adults. We report linkage of the canine cd locus to marker C29.002 on canine chromosome 29 at recombination fraction theta = 0.0 with a maximum LOD score of 24.68 in a series of informative outbred pedigrees derived from cd-affected Alaskan Malamutes. Conserved gene order between CFA29 and the long arm of human chromosome 8 argued for homology between the cd locus and the human achromatopsia locus, ACHM3, at 8q21-22. The canine homolog of the cyclic nucleotide-gated channel beta-subunit gene (CNGB3), responsible for the human ACHM3 disease phenotype, was mapped within the zero-recombination interval for the cd locus. A deletion removing all exons of canine CNGB3 was identified in cd-affected Alaskan Malamute-derived dogs. A missense mutation in exon 6 (D262N, nucleotide 784) within a conserved region of the same gene was detected in German Shorthaired Pointers affected with an allelic disorder. Identification of these canine disorders as homologs of human ACHM3 underscores the power of recent developments in canine genomics, and provides a valuable system for exploring disease mechanisms and evaluating potential therapeutic measures in disorders of cone photoreceptors.

Author List

Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan DR, Aguirre GD, Acland GM, Ostrander EA

Author

Danielle Sidjanin Maier PhD Nurse Practitioner in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Chromosome Mapping
Color Vision Defects
Cyclic Nucleotide-Gated Cation Channels
DNA
Dog Diseases
Dogs
Female
Genetic Linkage
Humans
In Situ Hybridization, Fluorescence
Ion Channels
Male
Mutation
Pedigree
Photoreceptor Cells
Retinal Cone Photoreceptor Cells
Retinal Diseases
Species Specificity