Epistasis and the sensitivity of phenotypic screens for beta thalassaemia

British Journal of Haematology
Bridget S PenmanDavid J Weatherall

Abstract

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-income and lower-middle 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-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 to detect carriers of 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 interactions between the carrier states for beta thalassaemia and alpha thalassaemia, glucose-6-phosphate dehydrogenase deficiency and Southeast Asian Ovalocytosis have the potential to reduce the sensitivity of OTOFTs for beta thalassaemia heterozygosity to below 70%. Our...Continue Reading

References

Mar 1, 1975·Journal of Medical Genetics·M Willcox
Jan 1, 1985·Clinical and Laboratory Haematology·G H MaudeG R Serjeant
Jun 1, 1987·Journal of Medical Genetics·D K BowdenJohn Clegg
Oct 1, 1985·Journal of Medical Genetics·L Maccioni, A Cao
Jul 21, 1973·British Medical Journal·H H Knox-MacaulayM E Pembrey
Apr 1, 1970·The Journal of Clinical Investigation·Y W Kan, D G Nathan
Mar 7, 1981·Lancet·David J WeatherallJohn Clegg
Nov 1, 1982·British Journal of Haematology·E KanavakisT Sophocleous
Mar 1, 1983·British Journal of Haematology·J S WainscoatDavid J Weatherall
Aug 1, 1983·Annals of Tropical Medicine and Parasitology·M WillcoxJ Brohult
Aug 1, 1981·Journal of Medical Genetics·C KattamisS Pootrakul
Feb 15, 2002·British Journal of Haematology·David J Weatherall
May 3, 2002·Clinical and Diagnostic Laboratory Immunology·Olga TapiaEllena M Peterson
Aug 12, 2003·Hemoglobin·Shaheen N KhanSheikh Riazuddin
Aug 15, 2003·Advances in Experimental Medicine and Biology·Iswari SetianingsihIta M Nainggolan
Jun 17, 2004·Blood·Frank P MockenhauptUlrich Bienzle
Aug 25, 2004·International Journal of Gynaecology and Obstetrics : the Official Organ of the International Federation of Gynaecology and Obstetrics·Supatra SirichotiyakulTheera Tongsong
Jun 27, 2006·Molecular and Biochemical Parasitology·Thomas N Williams
Nov 10, 2006·American Journal of Hematology·Goonnapa FucharoenKanokwan Sanchaisuriya
Jul 10, 2007·Nature Medicine·Michael A Matthay, Xiao Su
Dec 15, 2007·Journal of Medical Screening·Manju MamtaniHemant Kulkarni
Jun 24, 2008·Bulletin of the World Health Organization·Bernadette Modell, Matthew Darlison
Mar 27, 2012·The Lancet Infectious Diseases·Steve M TaylorRick M Fairhurst
May 15, 2013·Blood Reviews·Lydie Da CostaNarla Mohandas
May 30, 2013·Indian Journal of Human Genetics·Ankur G PatelSnehalata C Gupte

Citations

Sep 12, 2019·British Journal of Haematology·Subarna Chakravorty, Moira C Dick
Aug 27, 2019·Frontiers in Molecular Biosciences·Angela AllenAnuja Premawardhena

Related Concepts

Elliptocytosis, Hereditary
Deviation, Epistatic
Genetic Equilibrium
Deficiency of glucose-6-phosphate Dehydrogenase
Mass Screening
Osmotic Fragility Test
Thalassemia Minor
Anemia, Sickle Cell
Beta Thalassemia
Birth

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Related Papers

JPMA. the Journal of the Pakistan Medical Association
Muhammad Sajid Yazdani, Suhaib Ahmed
The British Journal of General Practice : the Journal of the Royal College of General Practitioners
Stirling BryanTheresa M Marteau
The Cochrane Database of Systematic Reviews
Kye Mon Min SweN S Nair
© 2021 Meta ULC. All rights reserved