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Epistasis and the sensitivity of phenotypic screens for beta thalassaemia.

Penman BS, Gupta S, Weatherall DJ - Br. J. Haematol. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, Oxford, UK.

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Related in: MedlinePlus

The combined impact of SAO, alpha thalassaemia frequency and G6PD deficiency on the sensitivity of one tube osmotic fragility tests for beta thalassaemia. The surfaces illustrate how the sensitivities of one tube osmotic fragility tests for beta thalassaemia change in males and females with changing frequencies of alpha thalassaemia (the ‘−α’ deletion) and the mutation responsible for Southeast Asian Ovalocytosis (SAO). g1 = 0·95, g2 = 0·75, g4 = 0·5, and g5 = 0. In both panels the population frequency of G6PD deficiency is 0.13. Marker ‘A’ indicates the maximum SAO and ‘−α’ frequencies that have been reported from the Northern coast of Papua New Guinea. Marker ‘B’ indicates the SAO frequency reported from Sumba Island, Indonesia, and a plausible Indonesian alpha thalassaemia frequency.
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fig04: The combined impact of SAO, alpha thalassaemia frequency and G6PD deficiency on the sensitivity of one tube osmotic fragility tests for beta thalassaemia. The surfaces illustrate how the sensitivities of one tube osmotic fragility tests for beta thalassaemia change in males and females with changing frequencies of alpha thalassaemia (the ‘−α’ deletion) and the mutation responsible for Southeast Asian Ovalocytosis (SAO). g1 = 0·95, g2 = 0·75, g4 = 0·5, and g5 = 0. In both panels the population frequency of G6PD deficiency is 0.13. Marker ‘A’ indicates the maximum SAO and ‘−α’ frequencies that have been reported from the Northern coast of Papua New Guinea. Marker ‘B’ indicates the SAO frequency reported from Sumba Island, Indonesia, and a plausible Indonesian alpha thalassaemia frequency.

Mentions: In Papua New Guinea, reported SAO frequencies range from 0·0005 to 0·074 (Patel et al, 2004); in Sumba Island, Indonesia, an SAO frequency of 0·057 has been reported (Shimizu et al, 2005). Even if SAO heterozygosity completely masks the osmotic fragility of beta thalassaemia carriers, such SAO frequencies alone will only reduce the sensitivity of OTOFTs as a test for beta thalassaemia to between 0·8 and 0·9 (Fig4).


Epistasis and the sensitivity of phenotypic screens for beta thalassaemia.

Penman BS, Gupta S, Weatherall DJ - Br. J. Haematol. (2014)

The combined impact of SAO, alpha thalassaemia frequency and G6PD deficiency on the sensitivity of one tube osmotic fragility tests for beta thalassaemia. The surfaces illustrate how the sensitivities of one tube osmotic fragility tests for beta thalassaemia change in males and females with changing frequencies of alpha thalassaemia (the ‘−α’ deletion) and the mutation responsible for Southeast Asian Ovalocytosis (SAO). g1 = 0·95, g2 = 0·75, g4 = 0·5, and g5 = 0. In both panels the population frequency of G6PD deficiency is 0.13. Marker ‘A’ indicates the maximum SAO and ‘−α’ frequencies that have been reported from the Northern coast of Papua New Guinea. Marker ‘B’ indicates the SAO frequency reported from Sumba Island, Indonesia, and a plausible Indonesian alpha thalassaemia frequency.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383351&req=5

fig04: The combined impact of SAO, alpha thalassaemia frequency and G6PD deficiency on the sensitivity of one tube osmotic fragility tests for beta thalassaemia. The surfaces illustrate how the sensitivities of one tube osmotic fragility tests for beta thalassaemia change in males and females with changing frequencies of alpha thalassaemia (the ‘−α’ deletion) and the mutation responsible for Southeast Asian Ovalocytosis (SAO). g1 = 0·95, g2 = 0·75, g4 = 0·5, and g5 = 0. In both panels the population frequency of G6PD deficiency is 0.13. Marker ‘A’ indicates the maximum SAO and ‘−α’ frequencies that have been reported from the Northern coast of Papua New Guinea. Marker ‘B’ indicates the SAO frequency reported from Sumba Island, Indonesia, and a plausible Indonesian alpha thalassaemia frequency.
Mentions: In Papua New Guinea, reported SAO frequencies range from 0·0005 to 0·074 (Patel et al, 2004); in Sumba Island, Indonesia, an SAO frequency of 0·057 has been reported (Shimizu et al, 2005). Even if SAO heterozygosity completely masks the osmotic fragility of beta thalassaemia carriers, such SAO frequencies alone will only reduce the sensitivity of OTOFTs as a test for beta thalassaemia to between 0·8 and 0·9 (Fig4).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, Oxford, UK.

Show MeSH
Related in: MedlinePlus