{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:27:31Z","timestamp":1790260051596,"version":"4.1.0"},"reference-count":18,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5777","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2006,5,26]]},"abstract":"<jats:p>We describe a pathogenetic mechanism underlying a variant form of the inherited blood disorder \u03b1 thalassemia. Association studies of affected individuals from Melanesia localized the disease trait to the telomeric region of human chromosome 16, which includes the \u03b1-globin gene cluster, but no molecular defects were detected by conventional approaches. After resequencing and using a combination of chromatin immunoprecipitation and expression analysis on a tiled oligonucleotide array, we identified a gain-of-function regulatory single-nucleotide polymorphism (rSNP) in a nongenic region between the \u03b1-globin genes and their upstream regulatory elements. The rSNP creates a new promoterlike element that interferes with normal activation of all downstream \u03b1-like globin genes. Thus, our work illustrates a strategy for distinguishing between neutral and functionally important rSNPs, and it also identifies a pathogenetic mechanism that could potentially underlie other genetic diseases.<\/jats:p>","DOI":"10.1126\/science.1126431","type":"journal-article","created":{"date-parts":[[2006,6,21]],"date-time":"2006-06-21T10:45:11Z","timestamp":1150886711000},"page":"1215-1217","source":"Crossref","is-referenced-by-count":240,"title":["A Regulatory SNP Causes a Human Genetic Disease by Creating a New Transcriptional Promoter"],"prefix":"10.1126","volume":"312","author":[{"given":"Marco","family":"De Gobbi","sequence":"first","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK."},{"name":"Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand."},{"name":"BACPAC Resources, Oakland Research Institute Children's Hospital, Oakland, CA, USA."},{"name":"Genome Science, Genomic Division, Lawrence Berkeley National Laboratory, CA, USA."},{"name":"Department of Anatomy and Cell Biology, Monash University, Melbourne, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vip","family":"Viprakasit","sequence":"additional","affiliation":[{"name":"Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK."},{"name":"Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand."},{"name":"BACPAC Resources, Oakland Research Institute Children's Hospital, Oakland, CA, USA."},{"name":"Genome Science, Genomic Division, Lawrence Berkeley National Laboratory, CA, USA."},{"name":"Department of Anatomy and Cell Biology, Monash University, Melbourne, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim R.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Medical 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V.V. is supported by the Thailand Research Fund."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1126431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T23:06:28Z","timestamp":1704841588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1126431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5,26]]},"references-count":18,"journal-issue":{"issue":"5777","published-print":{"date-parts":[[2006,5,26]]}},"alternative-id":["10.1126\/science.1126431"],"URL":"https:\/\/doi.org\/10.1126\/science.1126431","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.14579.374199","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.14579.375262","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,5,26]]}}}