NDLI: Genes of the Unfolded Protein Response Pathway Harbor Risk Alleles for Primary Open Angle Glaucoma

Content Provider	PubMed Central
Author	Carbone, Mary Anna Chen, Yuhong Hughes, Guy A. Weinreb, Robert N. Zabriskie, Norman A. Zhang, Kang Anholt, Robert R. H.
Editor	Toland, Amanda Ewart
Copyright Year	2011
Abstract	The statistical power of genome-wide association (GWA) studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG). Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG) remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR) upon overexpression of transgenic human glaucoma-associated myocilin (MYOC). We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.
Related Links	http://dx.doi.org/10.1371/journal.pone.0020649
Starting Page	20649
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	5
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-05-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Overexpression of Myocilin in the Drosophila Eye Activates the Unfolded Protein Response: Implications for Glaucoma

Transcriptional Regulation of VEGF-A by the Unfolded Protein Response Pathway

Risk Factors for Progressive Visual Field Loss in Primary Angle-Closure Glaucoma: A Retrospective Cohort Study

Mitochondrial Genome Analysis of Primary Open Angle Glaucoma Patients

Differences in Unfolded Protein Response Pathway Activation in the Lenses of Three Types of Cataracts

Comparison of Prelaminar Thickness between Primary Open Angle Glaucoma and Normal Tension Glaucoma Patients

Discovery of Genes Activated by the Mitochondrial Unfolded Protein Response (mtUPR) and Cognate Promoter Elements

Extracting Primary Open-Angle Glaucoma from Electronic Medical Records for Genetic Association Studies

Impact of Socioeconomic Status on the Diagnosis of Primary Open-Angle Glaucoma and Primary Angle Closure Glaucoma: A Nationwide Population-Based Study in Taiwan

Genes of the Unfolded Protein Response Pathway Harbor Risk Alleles for Primary Open Angle Glaucoma

Similar Documents

Overexpression of Myocilin in the Drosophila Eye Activates the Unfolded Protein Response: Implications for Glaucoma

Transcriptional Regulation of VEGF-A by the Unfolded Protein Response Pathway

Risk Factors for Progressive Visual Field Loss in Primary Angle-Closure Glaucoma: A Retrospective Cohort Study

Mitochondrial Genome Analysis of Primary Open Angle Glaucoma Patients

Differences in Unfolded Protein Response Pathway Activation in the Lenses of Three Types of Cataracts

Comparison of Prelaminar Thickness between Primary Open Angle Glaucoma and Normal Tension Glaucoma Patients

Discovery of Genes Activated by the Mitochondrial Unfolded Protein Response (mtUPR) and Cognate Promoter Elements

Extracting Primary Open-Angle Glaucoma from Electronic Medical Records for Genetic Association Studies

Impact of Socioeconomic Status on the Diagnosis of Primary Open-Angle Glaucoma and Primary Angle Closure Glaucoma: A Nationwide Population-Based Study in Taiwan

Genes of the Unfolded Protein Response Pathway Harbor Risk Alleles for Primary Open Angle Glaucoma