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You searched for subject:(Canine PRA). Showing records 1 – 3 of 3 total matches.

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Cornell University

1. Goldstein, Orly. Insight Into Sight: Deciphering The Heterogeneity Of Hereditary Retinal Degeneration In The Canine Population.

Degree: PhD, Veterinary Medicine, 2014, Cornell University

As of October 2013, around 285 million people are visually impaired worldwide. For an important subset of these, this visual impairment is genetic. That is, they have inherited mutant genes that prevent sight by affecting an element critical for vision. Understanding the genetic basis of these diseases offers insight into the mechanisms involved in photoreceptor development, function, and maintenance as well as significant potential for therapies addressed at cure or prevention. In recent decades, understanding of the cellular and molecular mechanisms of vision has expanded dramatically. In particular, many genes have been discovered that are vital for normal function of the retina, the delicate, multilayered, light-sensitive layer at the back of the eye that connects by the optic nerve to the brain. Retinitis pigmentosa (RP) is a subgroup of inherited eye diseases causing retinal degeneration. In the U.S.A alone, an estimated 100,000 people have inherited RP, either as an autosomal dominant, autosomal recessive, or X-linked disease. Among these, about 50% of cases of autosomal recessive RP cannot be explained by so far identified genes, and for many of the known genes, their role in vision is unclear. The dog also suffers from inherited eye diseases. The canine disease homolog of RP is referred to as Progressive Retinal Atrophy (PRA). Because of the unique population structure and genetic differences within and among the various breeds of dogs, this animal model offers a remarkable tool for discovering genetic mechanisms in vision and serves as a therapeutic model for potential gene therapy. In the present work, we have investigated nine different canine diseases (OSD, erd, prcd, cd, crd1, crd2, crd3, Basenji PRA, and Italian Greyhound PRA), characterized them, discovered the genes responsible for their phenotype, and determined the broad spectrum of breeds affected by them. These studies utilized classical genetic methods such as linkage and candidate gene approaches, and were expanded to employ Linkage Disequilibrium and Association Studies. We discovered two novel genes, PRCD and STK38L, both of which cause PRA in dogs, but had not previously been recognized as involved in vision or visual disorders, and thereby identified novel pathways critical for vision, as well as genes potentially responsible for human RP. We also identified novel mutations in six known genes (COL9A2, COL9A3, ADAM9, PDE6B, IQCB1, and SAG) that cause five different diseases, and thereby established new animal models for potential gene therapy in their human counterparts. We identified the exact deletion points of the cd disease in a broad spectrum of breeds affected by this disease, showing that they are all inherited Identical By Descent (IBD). We discovered the potential involvement of a microRNA in retinal degeneration in the Italian greyhound PRA, the first such evidence in a large animal model, and the first suggestion that retinal degeneration can be caused by alteration in gene expression regulated by microRNA. We developed screening… Advisors/Committee Members: Acland, Gregory Maurice (chair), Meyers-Wallen, Vicki N (committee member), Schimenti, John C. (committee member), Coonrod, Scott A. (committee member).

Subjects/Keywords: Retinal degeneration; Genetic mutation; Canine PRA

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APA (6th Edition):

Goldstein, O. (2014). Insight Into Sight: Deciphering The Heterogeneity Of Hereditary Retinal Degeneration In The Canine Population. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/36147

Chicago Manual of Style (16th Edition):

Goldstein, Orly. “Insight Into Sight: Deciphering The Heterogeneity Of Hereditary Retinal Degeneration In The Canine Population.” 2014. Doctoral Dissertation, Cornell University. Accessed March 06, 2021. http://hdl.handle.net/1813/36147.

MLA Handbook (7th Edition):

Goldstein, Orly. “Insight Into Sight: Deciphering The Heterogeneity Of Hereditary Retinal Degeneration In The Canine Population.” 2014. Web. 06 Mar 2021.

Vancouver:

Goldstein O. Insight Into Sight: Deciphering The Heterogeneity Of Hereditary Retinal Degeneration In The Canine Population. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/1813/36147.

Council of Science Editors:

Goldstein O. Insight Into Sight: Deciphering The Heterogeneity Of Hereditary Retinal Degeneration In The Canine Population. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36147


University of Cambridge

2. Hitti-Malin, Rebekkah. Elucidating the genetic basis of canine progressive retinal atrophies in several breeds of dog.

Degree: PhD, 2020, University of Cambridge

Canine progressive retinal atrophies (PRA) are a group of hereditary diseases characterised by rod and cone photoreceptor cell death in the retina. This study sought to elucidate novel PRA-associated variants of distinct forms of PRA in three breeds of dog: the Lhasa Apso (LA), Giant Schnauzer (GS) and Shetland Sheepdog (SS). A genome-wide association study identified a 1.3 Mb disease-associated region on canine chromosome 33 in LA dogs. Whole genome sequencing (WGS) analysis of a PRA-affected LA revealed a long interspersed nuclear element-1 (LINE-1) insertion in the predicted promoter region of the retinal candidate gene, IMPG2. Validation of the LINE-1 insertion determined it segregated with disease and was likely to be private to LA dogs. Comprehensive WGS analyses alone were utilised to determine PRA-associated mutations in a family of GS dogs, and in a single SS. For the GS breed, WGS was performed on two affected siblings and both non-affected parents. Successive filtering, for autosomal recessive deleterious variants, against 568 canine genomes identified a single nucleotide variant (SNV) in the gene encoding NECAP endocytosis associated 1 (NECAP1): c.544G > A (p.G182R). Screening 5,130 canids revealed only the three PRA-affected GS were homozygous for the SNV, yet heterozygotes were identified in the GS breed and in other breeds of German ancestry. NECAP1 has not previously been associated with retinal degeneration; however, these findings, in parallel with known gene function, indicate NECAP1 should be considered as a strong candidate for retinal degeneration research in other species. Following WGS analysis of the single SS against 176 controls of other breeds, a c.1222G > C (p.A408P) SNV in the Bardet-Biedl syndrome 2 gene (BBS2) was identified. In addition to PRA, homozygotes exhibited features including an upturned nose, unusual coat and dental defects, proposing a novel syndromic form of canine PRA. This research has elucidated three novel PRA-associated mutations for which diagnostic DNA tests have been developed, offering breeders the opportunity to avoid producing PRA-affected dogs. Since PRA shares clinical features to human retinitis pigmentosa (RP) and other phenotypically similar retinal diseases, this study may offer novel insights for consideration in human as well as canine retinal degeneration research and gene therapies.

Subjects/Keywords: Canine; Progressive retinal atrophy; Retinal degeneration; PRA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Hitti-Malin, R. (2020). Elucidating the genetic basis of canine progressive retinal atrophies in several breeds of dog. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.58690 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.818186

Chicago Manual of Style (16th Edition):

Hitti-Malin, Rebekkah. “Elucidating the genetic basis of canine progressive retinal atrophies in several breeds of dog.” 2020. Doctoral Dissertation, University of Cambridge. Accessed March 06, 2021. https://doi.org/10.17863/CAM.58690 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.818186.

MLA Handbook (7th Edition):

Hitti-Malin, Rebekkah. “Elucidating the genetic basis of canine progressive retinal atrophies in several breeds of dog.” 2020. Web. 06 Mar 2021.

Vancouver:

Hitti-Malin R. Elucidating the genetic basis of canine progressive retinal atrophies in several breeds of dog. [Internet] [Doctoral dissertation]. University of Cambridge; 2020. [cited 2021 Mar 06]. Available from: https://doi.org/10.17863/CAM.58690 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.818186.

Council of Science Editors:

Hitti-Malin R. Elucidating the genetic basis of canine progressive retinal atrophies in several breeds of dog. [Doctoral Dissertation]. University of Cambridge; 2020. Available from: https://doi.org/10.17863/CAM.58690 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.818186


University of Cambridge

3. Hitti-Malin, Rebekkah. Elucidating the Genetic Basis of Canine Progressive Retinal Atrophies in Several Breeds of Dog.

Degree: PhD, 2020, University of Cambridge

Canine progressive retinal atrophies (PRA) are a group of hereditary diseases characterised by rod and cone photoreceptor cell death in the retina. This study sought to elucidate novel PRA-associated variants of distinct forms of PRA in three breeds of dog: the Lhasa Apso (LA), Giant Schnauzer (GS) and Shetland Sheepdog (SS). A genome-wide association study identified a 1.3 Mb disease-associated region on canine chromosome 33 in LA dogs. Whole genome sequencing (WGS) analysis of a PRA-affected LA revealed a long interspersed nuclear element-1 (LINE-1) insertion in the predicted promoter region of the retinal candidate gene, IMPG2. Validation of the LINE-1 insertion determined it segregated with disease and was likely to be private to LA dogs. Comprehensive WGS analyses alone were utilised to determine PRA-associated mutations in a family of GS dogs, and in a single SS. For the GS breed, WGS was performed on two affected siblings and both non-affected parents. Successive filtering, for autosomal recessive deleterious variants, against 568 canine genomes identified a single nucleotide variant (SNV) in the gene encoding NECAP endocytosis associated 1 (NECAP1): c.544G>A (p.G182R). Screening 5,130 canids revealed only the three PRA-affected GS were homozygous for the SNV, yet heterozygotes were identified in the GS breed and in other breeds of German ancestry. NECAP1 has not previously been associated with retinal degeneration; however, these findings, in parallel with known gene function, indicate NECAP1 should be considered as a strong candidate for retinal degeneration research in other species. Following WGS analysis of the single SS against 176 controls of other breeds, a c.1222G>C (p.A408P) SNV in the Bardet-Biedl syndrome 2 gene (BBS2) was identified. In addition to PRA, homozygotes exhibited features including an upturned nose, unusual coat and dental defects, proposing a novel syndromic form of canine PRA. This research has elucidated three novel PRA-associated mutations for which diagnostic DNA tests have been developed, offering breeders the opportunity to avoid producing PRA-affected dogs. Since PRA shares clinical features to human retinitis pigmentosa (RP) and other phenotypically similar retinal diseases, this study may offer novel insights for consideration in human as well as canine retinal degeneration research and gene therapies.

Subjects/Keywords: Canine; Progressive retinal atrophy; Retinal degeneration; PRA

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Hitti-Malin, R. (2020). Elucidating the Genetic Basis of Canine Progressive Retinal Atrophies in Several Breeds of Dog. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/311598

Chicago Manual of Style (16th Edition):

Hitti-Malin, Rebekkah. “Elucidating the Genetic Basis of Canine Progressive Retinal Atrophies in Several Breeds of Dog.” 2020. Doctoral Dissertation, University of Cambridge. Accessed March 06, 2021. https://www.repository.cam.ac.uk/handle/1810/311598.

MLA Handbook (7th Edition):

Hitti-Malin, Rebekkah. “Elucidating the Genetic Basis of Canine Progressive Retinal Atrophies in Several Breeds of Dog.” 2020. Web. 06 Mar 2021.

Vancouver:

Hitti-Malin R. Elucidating the Genetic Basis of Canine Progressive Retinal Atrophies in Several Breeds of Dog. [Internet] [Doctoral dissertation]. University of Cambridge; 2020. [cited 2021 Mar 06]. Available from: https://www.repository.cam.ac.uk/handle/1810/311598.

Council of Science Editors:

Hitti-Malin R. Elucidating the Genetic Basis of Canine Progressive Retinal Atrophies in Several Breeds of Dog. [Doctoral Dissertation]. University of Cambridge; 2020. Available from: https://www.repository.cam.ac.uk/handle/1810/311598

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