Epistasis and the sensitivity of phenotypic screens for beta thalassaemia.
Bottom Line: For both of these functions it is vital that the screen performed is suitably sensitive.Here we introduce a population genetic framework within which to quantify the likely sensitivity and specificity of the OTOFT in different epidemiological contexts.Our results therefore caution against the widespread application of OTOFTs in regions where these erythrocyte variants co-occur.
Affiliation: Department of Zoology, University of Oxford, Oxford, UK.Show MeSH
Related in: MedlinePlus
Mentions: Figure1A compares reported mean corpuscular volume (MCV) values of red blood cells from individuals carrying different combinations of thalassaemic mutations (Sanna et al, 1980; Kanavakis et al, 1982; Melis et al, 1983; Rosatelli et al, 1984; Maccioni & Cao, 1985; Weatherall & Clegg, 2001), together with the MCVs of blood samples that tested either positive or negative in a OTOFT (Yazdani et al, 2008). The low MCV of carriers of either alpha or beta thalassaemia can be elevated by the coinheritance of alpha and beta thalassaemic mutations, due to the aforementioned ameliorative effect of balancing out globin chain synthesis, such that the range of MCV values for −α/−α ββT individuals overlaps the range of MCV values that tested negative in the OTOFT. This suggests there may be a risk of −α/−α ββT individuals being missed by the OTOFT screen.
Affiliation: Department of Zoology, University of Oxford, Oxford, UK.