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      Ocular morphologic traits in the American Cocker Spaniel may confer primary angle closure glaucoma susceptibility

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          Abstract

          Acute primary angle closure glaucoma is a potentially blinding ophthalmic emergency requiring prompt treatment to lower the elevated intraocular pressure in humans and dogs. The PACG in most of canine breeds is epidemiologically similar to humans with older and female patients overrepresented with the condition. The American Cocker Spaniel (ACS) is among the most common breeds observed with PACG development in dogs. This study initially sought to identify genetic risk factors to explain the high prevalence of PACG in ACSs by using a case–control breed-matched genome-wide association study. However, the GWAS failed to identify candidate loci associated with PACG in this breed. This study then assessed intrinsic ocular morphologic traits that may relate to PACG susceptibility in this breed. Normal ACSs without glaucoma have a crowded anterior ocular segment and narrow iridocorneal angle and ciliary cleft, which is consistent with anatomical risk factors identified in humans. The ACSs showed unique features consisting of posterior bowing of iris and longer iridolenticular contact, which mirrors reverse pupillary block and pigment dispersion syndrome in humans. The ACS could hold potential to serve as an animal model of naturally occurring PACG in humans.

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          Most cited references38

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          PLINK: a tool set for whole-genome association and population-based linkage analyses.

          Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.
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            qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots

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              Primary angle closure glaucoma: What we know and what we don't know.

              Primary angle-closure glaucoma (PACG) is a common cause of blindness. Angle closure is a fundamental pathologic process in PAGC. With the development of imaging devices for the anterior segment of the eye, a better understanding of the pathogenesis of angle closure has been reached. Aside from pupillary block and plateau iris, multiple-mechanisms are more common contributors for closure of the angle such as choroidal thickness and uveal expansion, which may be responsible for the presenting features of PACG. Recent Genome Wide Association Studies identified several new PACG loci and genes, which may shed light on the molecular mechanisms of PACG. The current classification systems of PACG remain controversial. Focusing the anterior chamber angle is a principal management strategy for PACG. Treatments to open the angle or halt the angle closure process such as laser peripheral iridotomy and/or iridoplasty, as well as cataract extraction, are proving their effectiveness. PACG may be preventable in the early stages if future research can identify which kind of angles and/or persons are more likely to benefit from prophylactic treatment. New treatment strategies like adjusting the psychological status and balancing the sympathetic-parasympathetic nerve activity, and innovative medicines are needed to improve the prognosis of PACG. In this review, we intend to describe current understanding and unknown aspects of PACG, and to share the clinical experience and viewpoints of the authors.
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                Author and article information

                Contributors
                smthomasy@ucdavis.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                8 November 2022
                8 November 2022
                2022
                : 12
                : 18980
                Affiliations
                [1 ]GRID grid.27860.3b, ISNI 0000 0004 1936 9684, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, , University of California-Davis, ; Davis, CA 95616 USA
                [2 ]GRID grid.27860.3b, ISNI 0000 0004 1936 9684, Department of Population Health and Reproduction, , University of California-Davis, ; Davis, CA 95616 USA
                [3 ]GRID grid.412807.8, ISNI 0000 0004 1936 9916, Vanderbilt Eye Institute, , Vanderbilt University Medical Center, ; Nashville, TN 37232 USA
                [4 ]GRID grid.5386.8, ISNI 000000041936877X, Department of Clinical Sciences, College of Veterinary Medicine, , Cornell University Ithaca, ; New York, 14853 USA
                [5 ]GRID grid.27860.3b, ISNI 0000 0004 1936 9684, Department of Ophthalmology & Vision Science, School of Medicine, , University of California-Davis, ; Davis, CA 95817 USA
                [6 ]Present Address: Small Animal Specialist Hospital, North Ryde, NSW 2113 Australia
                Article
                23238
                10.1038/s41598-022-23238-1
                9643544
                36348026
                f2caaa5f-7e39-448a-afdd-444bcfb17935
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 May 2022
                : 27 October 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: P30 EY12576
                Award ID: P30 EY12576
                Award Recipient :
                Funded by: AKC Canine Health Foundation
                Funded by: Jane Lin Fong Clinical Trial Support Fund
                Funded by: Center for Companion Animal Health, UC Davis
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                translational research,hereditary eye disease,glaucoma
                Uncategorized
                translational research, hereditary eye disease, glaucoma

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