Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration
A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder...
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| creator | Yang, Zhenglin Tong, Zongzhong Chen, Yuhong Zeng, Jiexi Lu, Fang Sun, Xufang Zhao, Chao Wang, Kevin Davey, Lisa Chen, Haoyu London, Nyall Muramatsu, Daisuke Salasar, Francesca Carmona, Ruben Kasuga, Daniel Wang, Xiaolei Bedell, Matthew Dixie, Manjuxia Zhao, Peiquan Yang, Ruifu Gibbs, Daniel Liu, Xiaoqi Li, Yan Li, Cai Li, Yuanfeng Campochiaro, Betsy Constantine, Ryan Zack, Donald J Campochiaro, Peter Fu, Yinbin Li, Dean Y Katsanis, Nicholas Zhang, Kang |
| description | A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits. |
| doi_str_mv | 10.1371/journal.pgen.1000836 |
| format | Article |
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Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1000836</identifier><identifier>PMID: 20140183</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Case-Control Studies ; Chromosomes, Human, Pair 10 - genetics ; Cohort Studies ; Development and progression ; Enzyme Assays ; Female ; Gene expression ; Gene Expression Regulation ; Genes ; Genetic aspects ; Genetic Predisposition to Disease ; Genetics and Genomics/Complex Traits ; Genetics and Genomics/Functional Genomics ; Genetics and Genomics/Gene Discovery ; Genetics and Genomics/Gene Function ; Genetics and Genomics/Genetics of Disease ; Genetics and Genomics/Medical Genetics ; Genomes ; Haplotypes ; Haplotypes - genetics ; High-Temperature Requirement A Serine Peptidase 1 ; Humans ; Identification and classification ; Luciferases - metabolism ; Macular degeneration ; Macular Degeneration - genetics ; Male ; Ophthalmology/Macular Disorders ; Pathogenesis ; Physiological aspects ; Plasmids ; Polymorphism, Single Nucleotide - genetics ; Proteins - genetics ; Proteins - metabolism ; Serine Endopeptidases - genetics ; Serine Endopeptidases - metabolism ; Studies ; Utah</subject><ispartof>PLoS genetics, 2010-02, Vol.6 (2), p.e1000836-e1000836</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>Yang et al. 2010</rights><rights>2010 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Yang Z, Tong Z, Chen Y, Zeng J, Lu F, et al. (2010) Genetic and Functional Dissection of HTRA1 and LOC387715 in Age-Related Macular Degeneration. PLoS Genet 6(2): e1000836. doi:10.1371/journal.pgen.1000836</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c763t-e161a259d292bbf979690005d8841827097effab1693d80c160e01ac5749209e3</citedby><cites>FETCH-LOGICAL-c763t-e161a259d292bbf979690005d8841827097effab1693d80c160e01ac5749209e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816682/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816682/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20140183$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Barsh, Gregory S.</contributor><creatorcontrib>Yang, Zhenglin</creatorcontrib><creatorcontrib>Tong, Zongzhong</creatorcontrib><creatorcontrib>Chen, Yuhong</creatorcontrib><creatorcontrib>Zeng, Jiexi</creatorcontrib><creatorcontrib>Lu, Fang</creatorcontrib><creatorcontrib>Sun, Xufang</creatorcontrib><creatorcontrib>Zhao, Chao</creatorcontrib><creatorcontrib>Wang, Kevin</creatorcontrib><creatorcontrib>Davey, Lisa</creatorcontrib><creatorcontrib>Chen, Haoyu</creatorcontrib><creatorcontrib>London, Nyall</creatorcontrib><creatorcontrib>Muramatsu, Daisuke</creatorcontrib><creatorcontrib>Salasar, Francesca</creatorcontrib><creatorcontrib>Carmona, Ruben</creatorcontrib><creatorcontrib>Kasuga, Daniel</creatorcontrib><creatorcontrib>Wang, Xiaolei</creatorcontrib><creatorcontrib>Bedell, Matthew</creatorcontrib><creatorcontrib>Dixie, Manjuxia</creatorcontrib><creatorcontrib>Zhao, Peiquan</creatorcontrib><creatorcontrib>Yang, Ruifu</creatorcontrib><creatorcontrib>Gibbs, Daniel</creatorcontrib><creatorcontrib>Liu, Xiaoqi</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Li, Cai</creatorcontrib><creatorcontrib>Li, Yuanfeng</creatorcontrib><creatorcontrib>Campochiaro, Betsy</creatorcontrib><creatorcontrib>Constantine, Ryan</creatorcontrib><creatorcontrib>Zack, Donald J</creatorcontrib><creatorcontrib>Campochiaro, Peter</creatorcontrib><creatorcontrib>Fu, Yinbin</creatorcontrib><creatorcontrib>Li, Dean Y</creatorcontrib><creatorcontrib>Katsanis, Nicholas</creatorcontrib><creatorcontrib>Zhang, Kang</creatorcontrib><title>Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.</description><subject>Aged</subject><subject>Case-Control Studies</subject><subject>Chromosomes, Human, Pair 10 - genetics</subject><subject>Cohort Studies</subject><subject>Development and progression</subject><subject>Enzyme Assays</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics and Genomics/Complex Traits</subject><subject>Genetics and Genomics/Functional Genomics</subject><subject>Genetics and Genomics/Gene Discovery</subject><subject>Genetics and Genomics/Gene Function</subject><subject>Genetics and Genomics/Genetics of Disease</subject><subject>Genetics and Genomics/Medical Genetics</subject><subject>Genomes</subject><subject>Haplotypes</subject><subject>Haplotypes - genetics</subject><subject>High-Temperature Requirement A Serine Peptidase 1</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Luciferases - metabolism</subject><subject>Macular degeneration</subject><subject>Macular Degeneration - genetics</subject><subject>Male</subject><subject>Ophthalmology/Macular Disorders</subject><subject>Pathogenesis</subject><subject>Physiological aspects</subject><subject>Plasmids</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Serine Endopeptidases - genetics</subject><subject>Serine Endopeptidases - metabolism</subject><subject>Studies</subject><subject>Utah</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVk12L1DAUhoso7jr6D0QLguJFx3y0TXIjDIPuDgwOrKtXQkjTk06GTjObtKL_3szHLlPwQslFkpPnfZOc5CTJS4ymmDL8YeMG36l2umugm2KEEKflo-QSFwXNWI7yx2fji-RZCBuEaMEFe5pcEIRzhDm9TH5cQQe91anq6tQMne6ti65pbUOAwyR1Jr2-vZnhA7JczSlnDBep7VLVQOahVT3U6VbpoVU-rSGeB7zaS58nT4xqA7w49ZPk2-dPt_PrbLm6Wsxny0yzkvYZ4BIrUoiaCFJVRjBRinifouY8x5wwJBgYoypcClpzpHGJAGGlC5YLggTQSfL66LtrXZCnxASJKaYFQoKUkVgcidqpjdx5u1X-t3TKykPA-UYqH9PQggRuBFEFUtiYnBdUoLzSVBiic0IrWkevj6fdhmoLtYau96odmY5XOruWjfspCcdlyUk0eHcy8O5ugNDLrQ0a2lZ14IYgGaWClpTQSL45ko2KJ7OdcdFQ72k5IwTlGOfxjpNk-hcqthq2VrsOjI3xkeD9SBCZHn71jRpCkIuvN__Bfvl3dvV9zL49Y9eg2n4dXDvs_00Yg_kR1N6F4ME8ZBojua-E-weX-0qQp0qIslfnr_Qguv_69A8hHf8n</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Yang, Zhenglin</creator><creator>Tong, Zongzhong</creator><creator>Chen, Yuhong</creator><creator>Zeng, Jiexi</creator><creator>Lu, Fang</creator><creator>Sun, Xufang</creator><creator>Zhao, Chao</creator><creator>Wang, Kevin</creator><creator>Davey, Lisa</creator><creator>Chen, Haoyu</creator><creator>London, Nyall</creator><creator>Muramatsu, Daisuke</creator><creator>Salasar, Francesca</creator><creator>Carmona, Ruben</creator><creator>Kasuga, Daniel</creator><creator>Wang, Xiaolei</creator><creator>Bedell, Matthew</creator><creator>Dixie, Manjuxia</creator><creator>Zhao, Peiquan</creator><creator>Yang, Ruifu</creator><creator>Gibbs, Daniel</creator><creator>Liu, Xiaoqi</creator><creator>Li, Yan</creator><creator>Li, Cai</creator><creator>Li, Yuanfeng</creator><creator>Campochiaro, Betsy</creator><creator>Constantine, Ryan</creator><creator>Zack, Donald J</creator><creator>Campochiaro, Peter</creator><creator>Fu, Yinbin</creator><creator>Li, Dean Y</creator><creator>Katsanis, Nicholas</creator><creator>Zhang, Kang</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100201</creationdate><title>Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration</title><author>Yang, Zhenglin ; Tong, Zongzhong ; Chen, Yuhong ; Zeng, Jiexi ; Lu, Fang ; Sun, Xufang ; Zhao, Chao ; Wang, Kevin ; Davey, Lisa ; Chen, Haoyu ; London, Nyall ; Muramatsu, Daisuke ; Salasar, Francesca ; Carmona, Ruben ; Kasuga, Daniel ; Wang, Xiaolei ; Bedell, Matthew ; Dixie, Manjuxia ; Zhao, Peiquan ; Yang, Ruifu ; Gibbs, Daniel ; Liu, Xiaoqi ; Li, Yan ; Li, Cai ; Li, Yuanfeng ; Campochiaro, Betsy ; Constantine, Ryan ; Zack, Donald J ; Campochiaro, Peter ; Fu, Yinbin ; Li, Dean Y ; Katsanis, Nicholas ; Zhang, Kang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c763t-e161a259d292bbf979690005d8841827097effab1693d80c160e01ac5749209e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Aged</topic><topic>Case-Control Studies</topic><topic>Chromosomes, Human, Pair 10 - 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Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20140183</pmid><doi>10.1371/journal.pgen.1000836</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7404 |
| ispartof | PLoS genetics, 2010-02, Vol.6 (2), p.e1000836-e1000836 |
| issn | 1553-7404 1553-7390 1553-7404 |
| language | eng |
| recordid | cdi_plos_journals_1313500926 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Public Library of Science (PLoS) |
| subjects | Aged Case-Control Studies Chromosomes, Human, Pair 10 - genetics Cohort Studies Development and progression Enzyme Assays Female Gene expression Gene Expression Regulation Genes Genetic aspects Genetic Predisposition to Disease Genetics and Genomics/Complex Traits Genetics and Genomics/Functional Genomics Genetics and Genomics/Gene Discovery Genetics and Genomics/Gene Function Genetics and Genomics/Genetics of Disease Genetics and Genomics/Medical Genetics Genomes Haplotypes Haplotypes - genetics High-Temperature Requirement A Serine Peptidase 1 Humans Identification and classification Luciferases - metabolism Macular degeneration Macular Degeneration - genetics Male Ophthalmology/Macular Disorders Pathogenesis Physiological aspects Plasmids Polymorphism, Single Nucleotide - genetics Proteins - genetics Proteins - metabolism Serine Endopeptidases - genetics Serine Endopeptidases - metabolism Studies Utah |
| title | Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T04%3A44%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genetic%20and%20functional%20dissection%20of%20HTRA1%20and%20LOC387715%20in%20age-related%20macular%20degeneration&rft.jtitle=PLoS%20genetics&rft.au=Yang,%20Zhenglin&rft.date=2010-02-01&rft.volume=6&rft.issue=2&rft.spage=e1000836&rft.epage=e1000836&rft.pages=e1000836-e1000836&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1000836&rft_dat=%3Cgale_plos_%3EA220411431%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=733936323&rft_id=info:pmid/20140183&rft_galeid=A220411431&rft_doaj_id=oai_doaj_org_article_e8f92a50a1ff4853904bc39f2c423b3d&rfr_iscdi=true |