{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:29:53Z","timestamp":1760189393077,"version":"3.37.3"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,17]],"date-time":"2014-12-17T00:00:00Z","timestamp":1418774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["096063"],"award-info":[{"award-number":["096063"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC advanced investigator (DIVERSITY) 268904"],"award-info":[{"award-number":["ERC advanced investigator (DIVERSITY) 268904"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anthony Cerami and Ann Dunne Foundation for World Health"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Genetic disorders of haemoglobin, particularly the sickle cell diseases and the alpha and beta thalassaemias, are the commonest inherited disorders worldwide. The majority of affected births occur in low\u2010income and lower\u2010middle income countries. Screening programmes are a vital tool to counter these haemoglobinopathies by: (i) identifying individual carriers and allowing them to make informed reproductive choices, and (ii) generating population level gene\u2010frequency estimates, to help ensure the optimal allocation of public health resources. For both of these functions it is vital that the screen performed is suitably sensitive. One popular first\u2010stage screening option to detect carriers of beta thalassaemia in low\u2010income countries is the One Tube Osmotic Fragility Test (<jats:styled-content style=\"fixed-case\">OTOFT<\/jats:styled-content>). Here we introduce a population genetic framework within which to quantify the likely sensitivity and specificity of the <jats:styled-content style=\"fixed-case\">OTOFT<\/jats:styled-content> in different epidemiological contexts. We demonstrate that interactions between the carrier states for beta thalassaemia and alpha thalassaemia, glucose\u20106\u2010phosphate dehydrogenase deficiency and Southeast Asian Ovalocytosis have the potential to reduce the sensitivity of <jats:styled-content style=\"fixed-case\">OTOFT<\/jats:styled-content>s for beta thalassaemia heterozygosity to below 70%. Our results therefore caution against the widespread application of <jats:styled-content style=\"fixed-case\">OTOFT<\/jats:styled-content>s in regions where these erythrocyte variants co\u2010occur.<\/jats:p>","DOI":"10.1111\/bjh.13241","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T06:48:48Z","timestamp":1418971728000},"page":"117-128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Epistasis and the sensitivity of phenotypic screens for beta thalassaemia"],"prefix":"10.1111","volume":"169","author":[{"given":"Bridget S.","family":"Penman","sequence":"first","affiliation":[{"name":"Department of Zoology University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunetra","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Weatherall","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine Oxford University John Radcliffe Hospital Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,12,17]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"173","article-title":"Masked deficit of vitamin B12 in the patient with heterozygous \u03b2\u2010thalassemia and spastic paraparesis","volume":"104","author":"Bili\u0107 E.","year":"2004","journal-title":"Acta Neurologica Belgica"},{"key":"e_1_2_7_3_1","first-page":"265","article-title":"NESTROFT as a screening test for detection of Beta\u2010thalassemia trait","volume":"45","author":"Bobhate S.K.","year":"2002","journal-title":"Indian Journal of Pathology & 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