Canine RD3 Mutation Establishes Rod-Cone Dysplasia Type 2 (rcd2) as Ortholog of Human and Murine rd3
Penn collection
Degree type
Discipline
Subject
splice variant
retinal degeneration
mouse exon
affected dog
rna
polynucleotide
information biomacromolecule
bac clone
nucleic acid
opossum genome
proline
northern blot analysis
amino acid
arginine
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Eye Diseases
Medical Cell Biology
Medical Genetics
Ophthalmology
Optometry
Veterinary Medicine
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Abstract
Rod-cone dysplasia type 2 (rcd2) is an autosomal recessive disorder that segregates in collie dogs. Linkage disequilibrium and meiotic linkage mapping were combined to take advantage of population structure within this breed and to fine map rcd2 to a 230-kb candidate region that included the gene C1orf36 responsible for human and murine rd3, and within which all affected dogs were homozygous for one haplotype. In one of three identified canine retinal RD3 splice variants, an insertion was found that cosegregates with rcd2 and is predicted to alter the last 61 codons of the normal open reading frame and further extend the open reading frame. Thus, combined meiotic linkage and LD mapping within a single canine breed can yield critical reduction of the disease interval when appropriate advantage is taken of within-breed population structure. This should permit a similar approach to tackle other hereditary traits that segregate in single closed populations.