{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:08:32Z","timestamp":1776938912722,"version":"3.51.4"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Genomics"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Sickle cell disease (SCD) is an important cause of under-five mortality. Tanzania is the 5th country in the world with the highest births prevalence of SCD individuals. Significant advances in the neonatal diagnosis of SCD using rapid point-of-care testing have been made. However genetic confirmation is still required for positive cases, in uncertain cases, in multiply transfused patients, to resolve compound heterozygosity (Hb S\/ \u03b2<jats:sup>0<\/jats:sup> Thal or Hb S\/ \u03b2<jats:sup>+<\/jats:sup> thal) not uncommon in the coastal regions of East Africa and increasingly also for pre-marital counselling and potentially for future curative approaches such as gene therapy. The currently available DNA tests are prohibitively expensive. Here, we describe an easy-to-use, affordable and accurate \u03b2-globin sequencing approach that can be easily integrated within existing NBS for SCD and other haemoglobinopathies especially in Low- and Middle-income Countries.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Aim<\/jats:title>\n                <jats:p>To evaluate an affordable DNA technology for the diagnosis of Sickle cell disease and other haemoglobinopathies in a resource-limited setting.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Laboratory-based validation study was conducted by Muhimbili University of Health and Allied Sciences and the University of Oxford involving sequencing of the entire \u03b2 -haemoglobin locus using the Oxford Nanopore MinION platform. A total number of 36 Dried blood spots and whole blood samples were subjected to conventional protein-based methods (isoelectric focusing, HPLC), and\/or sequenced by the Sanger method as comparators.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Sequencing results for SCD using the MinION were 100% concordant with those from the Sanger method. In addition, the long-read DNA sequencing method enabled the resolution of cases with unusual phenotypes which make up 1% of all children in Tanzania. The cost is \u00a311\/ sample for consumables, which is cheaper compared to other sequencing platforms.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This is the first report of a comprehensive single DNA assay as a definitive diagnostic test for SCD and other haemoglobinopathies. The test is fast, precise, accurate and affordable.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12864-021-08220-x","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T18:02:51Z","timestamp":1639677771000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Using DNA testing for the precise, definite, and low-cost diagnosis of sickle cell disease and other Haemoglobinopathies: findings from Tanzania"],"prefix":"10.1186","volume":"22","author":[{"given":"Heavenlight","family":"Christopher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Burns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Josephat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Makani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Schuh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siana","family":"Nkya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"8220_CR1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S0065-3233(08)60287-9","volume":"40","author":"WA Eaton","year":"1990","unstructured":"Eaton WA, Hofrichter J. Sickle cell haemoglobin polymerization. Adv Protein Chem. 1990;40:63\u2013279 Accessed December 2, 2018. http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/2195851.","journal-title":"Adv Protein Chem"},{"key":"8220_CR2","doi-asserted-by":"publisher","unstructured":"Old JM. Screening and genetic diagnosis of haemoglobin disorders. Blood Rev. 2003. https:\/\/doi.org\/10.1016\/S0268-960X(02)00061-9 Published online.","DOI":"10.1016\/S0268-960X(02)00061-9"},{"key":"8220_CR3","doi-asserted-by":"publisher","unstructured":"Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global Burden of Sickle Cell Anaemia in Children under Five, 2010-2050: modelling based on demographics, excess mortality, and interventions. Plos Med 2013;10(7). doi:https:\/\/doi.org\/10.1371\/journal.pmed.1001484.","DOI":"10.1371\/journal.pmed.1001484"},{"issue":"10091","key":"8220_CR4","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/S0140-6736(17)30193-9","volume":"390","author":"RE Ware","year":"2017","unstructured":"Ware RE, de Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease. Lancet. 2017;390(10091):311\u201323. https:\/\/doi.org\/10.1016\/S0140-6736(17)30193-9.","journal-title":"Lancet"},{"issue":"9861","key":"8220_CR5","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/S0140-6736(12)61229-X","volume":"381","author":"FB Piel","year":"2013","unstructured":"Piel FB, Patil AP, Howes RE, et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. 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C. Informed consent was obtained from all the participants including consent from parents of participants below 16\u2009years. All the methods were performed in accordance with MUHAS research and publications committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent for publication of the clinical details was obtained from both the adult study participants and consent from parents of the children below 18\u2009years. A copy of consent form is available to review by the Editor.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"902"}}