https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)61229-X.pdf

Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates.

It has been 100 years since the first report of sickle haemoglobin (HbS). More than 50 years ago, it was suggested that the gene responsible for this disorder could reach high frequencies because of resistance conferred against malaria by the heterozygous carrier state. This traditional example of balancing selection is known as the 'malaria hypothesis'. However, the geographical relationship between the transmission intensity of malaria and associated HbS burden has never been formally investigated on a global scale. Here, we use a comprehensive data assembly of HbS allele frequencies to generate the first evidence-based map of the worldwide distribution of the gene in a Bayesian geostatistical framework. We compare this map with the pre-intervention distribution of malaria endemicity, using a novel geostatistical area-mean comparison. We find geographical support for the malaria hypothesis globally; the relationship is relatively strong in Africa but cannot be resolved in the Americas or in Asia.

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Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis

Publisher Summary This chapter reviews that spectacular progress has been made in the recognition and study of biological differences between hemoglobin types. Many aspects of variations in hemoglobins such as the worldwide distribution of human hemoglobin types and their epidemiologic implications, animal hemoglobin types, and others have not been discussed. It may be expected that through the continuous efforts of investigators of various backgrounds, the next decade will prove as fertile as the last. The chapter discusses that the biochemist and geneticist will need to ask in what precise way the normal and abnormal hemoglobin types are synthesized. Others will continue their efforts to relate structural abnormalities and functional aberrations. The chapter explores that thalassemia has remained one of the most challenging disease states and presents a number of puzzles that are of importance and interest to the general physician, the hematologist, the pediatrician, the biochemist, the geneticist, the epidemiologist, and perhaps even the geographer, historian, and others. The same seems true for the fetal hemoglobin as it occurs in the newborn and in adults under various hematologic abnormalities; the function of this normal hemoglobin type, although the senior under the hemoglobin variants, is still incompletely known.

Normal and abnormal human hemoglobins.

Haemoglobin C (HbC) is one of the commonest structural haemoglobin variants in human populations. Although HbC causes mild clinical complications, its diagnosis and genetic counselling are important to prevent inheritance with other haemoglobinopathies. Little is known about its contemporary distribution and the number of newborns affected. We assembled a global database of population surveys. We then used a Bayesian geostatistical model to create maps of HbC frequency across Africa and paired our predictions with high-resolution demographics to calculate heterozygous (AC) and homozygous (CC) newborn estimates and their associated uncertainty. Data were too sparse outside Africa for this methodology to be applied. The highest frequencies were found in West Africa but HbC was commonly found in other parts of the continent. The expected annual numbers of AC and CC newborns in Africa were 672,117 (interquartile range (IQR): 642,116-705,163) and 28,703 (IQR: 26,027-31,958), respectively. These numbers are about two times previous estimates.

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The distribution of haemoglobin C and its prevalence in newborns in Africa

(1997). International Hemoglobin Information Center Variant List. Hemoglobin: Vol. 21, No. 6, pp. 505-506.

S H Boyer

Papers

A survey of hemoglobins in the Republic of Chad and characterization of hemoglobin Chad:alpha-2-23Glu--Lys-beta-2.