COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia

Goldstein, Orly; Guyon, Richard; Kukekova, Anna V.; Кузнецова, Т. Н.; Pearce-Kelling, Susan E.; Johnson, Jennifer L.; Aguirre, Gustavo D.; Acland, Gregory M.

doi:10.1007/s00335-010-9276-4

Cited by 50 publications

(78 citation statements)

References 25 publications

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“…Oculoskeletal dysplasia segregates as an autosomal recessive trait in Labrador Retriever and Samoyed dog breeds [Goldstein et al, 2010]. Two different causative loci have been identified in these breeds: drd1 and drd2.…”

Section: Discussionmentioning

confidence: 99%

A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome

Baker¹,

Booth²,

Fillman³

et al. 2011

American J of Med Genetics Pt A

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Stickler syndrome is characterized by ocular, auditory, skeletal, and orofacial abnormalities. We describe a family with autosomal recessive Stickler syndrome. The main clinical findings consisted of high myopia, vitreoretinal degeneration, retinal detachment, hearing loss, and short stature. Affected family members were found to have a homozygous loss-of-function mutation in COL9A2, c.843_c.846 + 4del8. A family with autosomal recessive Stickler syndrome was previously described and found to have a homozygous loss-of-function mutation in COL9A1. COL9A1, COL9A2, and COL9A3 code for collagen IX. All three collagen IX α chains, α1, α2, and α3, are needed for formation of functional collagen IX molecule. In dogs, two causative loci have been identified in autosomal recessive oculoskeletal dysplasia. This dysplasia resembles Stickler syndrome. Recently, homozygous loss-of-function mutations in COL9A2 and COL9A3 were found to co-segregate with the loci. Together the data from the present study and the previous studies suggest that loss-of-function mutations in any of the collagen IX genes can cause autosomal recessive Stickler syndrome.

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Section: Discussionmentioning

confidence: 99%

A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome

Baker¹,

Booth²,

Fillman³

et al. 2011

American J of Med Genetics Pt A

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“…Nonsyndromic forms have been reported in several breeds [e.g., Labrador retrievers (Barnett et al 1970) and Bedlington terriers (Rubin 1968)], but the underlying genetic causes are unknown. On the other hand, syndromic retinal dysplasia in Labrador retrievers (osd1) and Samoyeds (osd2) are nonallelic oculoskeletal disorders that model autosomal recessive Stickler syndrome in man; they are caused by mutations in COL9A3 and COL9A2 , respectively, both of which code for components of the type IX collagen fibril (Goldstein et al 2010a; Meyers et al 1983; Nelson and MacMillan 1983). …”

Section: Inherited Retinal Diseases In Dogs: Diverse Phenotypic Groupsmentioning

confidence: 99%

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

2011

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Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.

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“…Syndromic retinal dysplasia in Labrador Retrievers and Samoyeds are oculoskeletal disorders that model autosomal recessive Stickler syndrome in humans (Goldstein et al 2010a). Another developmental disorder is Collie eye anomaly (CEA) variably affecting the retina-choroid-scleral complex ranging from choroidal hypoplasia, scleral coloboma to retinal detachment.…”

Section: Phenotypic Characteristics Of Canine Rdsmentioning

confidence: 99%

Inherited retinal diseases in dogs: advances in gene/mutation discovery

Miyadera

2014

The Journal of Animal Genetics

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1. Inherited retinal diseases (RDs) are vision-threatening conditions affecting humans as well as many domestic animals. Through many years of clinical studies of the domestic dog population, a wide array of RDs has been phenotypically characterized. Extensive effort to map the causative gene and to identify the underlying mutation followed. Through candidate gene, linkage analysis, genome-wide association studies, and more recently, by means of next-generation sequencing, as many as 31 mutations in 24 genes have been identified as the underlying cause for canine RDs. Most of these genes have been associated with human RDs providing opportunities to study their roles in the disease pathogenesis and in normal visual function. The canine model has also contributed in developing new treatments such as gene therapy which has been clinically applied to human patients. Meanwhile, with increasing knowledge of the molecular architecture of RDs in different subpopulations of dogs, the conventional understanding of RDs as a simple monogenic disease is beginning to change. Emerging evidence of modifiers that alters the disease outcome is complicating the interpretation of DNA tests. In this review, advances in the gene/mutation discovery approaches and the emerging genetic complexity of canine RDs are discussed.

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COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia

Cited by 50 publications

References 25 publications

A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome

A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

Inherited retinal diseases in dogs: advances in gene/mutation discovery

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