Skip to main content
  • Oral presentation
  • Open access
  • Published:

Epistasis and the sensitivity of phenotypic screens for beta thalassaemia

Severe forms of alpha and beta thalassaemia have been estimated to affect approximately 68000 births annually. Individuals who carry thalassaemic genes are protected against death from malaria infection; the global distribution of thalassaemic genes thus matches the historical distribution of malaria.

Screening programmes are a vital tool to counter the thalassaemias by:

(i) identifying individual carriers and allowing them to make informed reproductive choices, and (ii) generating population level gene-frequency 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-stage screening option for beta thalassaemia in low-income countries is the One Tube Osmotic Fragility Test (OTOFT). Here we introduce a population genetic framework within which to quantify the likely sensitivity and specificity of the OTOFT in different epidemiological contexts. We demonstrate that the co-occurrence of alpha thalassaemia, and other malaria related erythrocyte poly-morphisms such as Southeast Asian Ovalocytosis and glucose-6-phosphate dehydrogenase deficiency, could reduce the sensitivity of OTOFTs for beta thalassaemia to below 70%. Our results highlight a potential hazard of the widespread application of OTOFTs and emphasize the fact that the public health impact of any single genetic adaptation to malaria cannot be considered in isolation.

Author information

Authors and Affiliations


Rights and permissions

This article is published under license to BioMed Central Ltd. 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 work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Penman, B., Gupta, S. & Weatherall, D. Epistasis and the sensitivity of phenotypic screens for beta thalassaemia. Malar J 13 (Suppl 1), O13 (2014).

Download citation

  • Published:

  • DOI: