COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia.
Oculoskeletal dysplasia segregates as an autosomal recessive trait in the Labrador retriever and Samoyed canine breeds, in which the causative loci have been termed drd1 and drd2, respectively. Affected dogs exhibit short-limbed dwarfism and severe ocular defects. The disease phenotype resembles human hereditary arthro-ophthalmopathies such as Stickler and Marshall syndromes, although these disorders are usually dominant. Linkage studies mapped drd1 to canine chromosome 24 and drd2 to canine chromosome 15. Positional candidate gene analysis then led to the identification of a 1-base insertional mutation in exon 1 of COL9A3 that cosegregates with drd1 and a 1,267-bp deletion mutation in the 5' end of COL9A2 that cosegregates with drd2. Both mutations affect the COL3 domain of the respective gene. Northern analysis showed that RNA expression of the respective genes was reduced in affected retinas. These models offer potential for studies such as protein-protein interactions between different members of the collagen gene family, regulation and expression of these genes in retina and cartilage, and even opportunities for gene therapy.
Goldstein
Orly
O
Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853, USA.
Guyon
Richard
R
Kukekova
Anna
A
Kuznetsova
Tatyana N
TN
Pearce-Kelling
Susan E
SE
Johnson
Jennifer
J
Aguirre
Gustavo D
GD
Acland
Gregory M
GM
D000818:Animals; D000831:Animals, Newborn; D001168:Arthritis / Q000235:genetics / Q000662:veterinary; D001483:Base Sequence; D002386:Cataract / Q000235:genetics / Q000662:veterinary; D024081:Collagen Type IX / Q000235:genetics*; D024161:Collagen Type XI / Q000172:deficiency; D003240:Connective Tissue Diseases / Q000235:genetics / Q000662:veterinary; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000662:veterinary; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D004392:Dwarfism / Q000150:complications / Q000235:genetics*; D015785:Eye Diseases, Hereditary / Q000150:complications / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000662:veterinary; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics / Q000662:veterinary; D010375:Pedigree; D012163:Retinal Detachment / Q000235:genetics / Q000662:veterinary
D024081:Collagen Type IX; D024161:Collagen Type XI