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

The sickle cell (HbS) gene occurs at a variable frequency in the Middle Eastern Arab countries, with characteristic distribution patterns and representing an overall picture of blood genetic disorders in the region. The origin of the gene has been debated, but studies using β-globin gene haplotypes have ascertained that there were multiple origins for HbS. In some regions the HbS gene is common and exhibits polymorphism, while the reverse is true in others. A common causative factor for the high prevalence and maintenance of HbS and thalassaemia genes is malaria endemicity. The HbS gene also co-exists with other haemoglobin variants and thalassaemia genes and the resulting clinical state is referred to as sickle cell disease (SCD). In the Middle Eastern Arab countries, the clinical picture of SCD expresses two distinct forms, the benign and the severe forms, which are related to two distinct β-globin gene haplotypes. These are referred to as the Saudi-Indian and the Benin haplotypes, respectively. In a majority of the Middle Eastern Arab countries the HbS is linked to the Saudi-Indian haplotype, while in others it is linked to the Benin haplotype. This review outlines the frequency, distribution, clinical feature, management and prevention as well as gene interactions of the HbS genes with other haemoglobin disorders in the Middle Eastern Arab countries.

Sickle cell disease in Middle East Arab countries

Hemoglobin E, an anomaly of the β-chain of human hemoglobin, is widely distributed in Southeast Asia and adjacent areas. In some populations of Southeast Asia the frequency of the gene responsible for the production of HbE reaches values near 0.3. In view of the probable disadvantage of the HbE homozygote and the certain disadvantage of the double heterozygote for the HbE and β-thalassemia genes an advantage of the heterozygote has to be postulated in order to explain the high gene frequencies. There is some evidence for and against malaria protection being the factor conveying heterozygote advantage. Data concerning genotype fitnesses in the triallelic system involving HbA, HbE and β-thalassemia are scanty. Crude fitness data based on clinical observations and equilibrium calculations indicate that the system is unstable. Dynamic models of the three genes suggest that the HbE gene is replacing the β-thalassemia gene in most Southeast Asian populations. The distribution of HbE and that of the austroasiatic group of languages are similar. This and several other aspects of the geographic and ethnic distribution of HbE are discussed in the last section of this review.

Hemoglobin E: distribution and population dynamics.

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.

/pdf/the-distribution-of-haemoglobin-c-and-its-prevalence-in-33ck17aikw.pdf

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

The populations of two Western Desert Egyptian oases have been studied for various genetic markers of the blood and some anthropological characters. Hb AS was found in 9%. Blood group frequencies were

Genetic markers and anthropometry in the populations of the Egyptian oases of El-Kharga and El-Dakhla.

Anthropological studies were done on 1276 Libyans from the Mediterranean cities of Tripoli and Benghazi, and from Sabha southward in The Sahara. The incidences of hemoglobin (Hb)-S and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were low in the coastal areas and significantly high in Sabha. Hb-C occurred sporadically in Tripoli and Sabha, and was absent from Benghazi in the east. One case of Hb-J Benghazi was noted. There were no significant differences in the ABO blood group and Rh0 (D) type distributions in the three localities. G-6-PD gene GdA frequency was significantly high in Sabha. The lowest value of 6-phosphogluconate dehydrogenase (6-PGD) gene PGDA frequency and highest value of the gene PGDC were in Sabha. Adenylate kinase (AK) gene AK2 was only detectable in Tripoli. Acid phosphatase (AP) gene Pa frequency in Sabha was more than twice that in Tripoli and Benghazi, while Pc was distinctly lower in Sabha than in the northern cities. Haptoglobin gene Hp1 frequency was almost identical in all areas. Anthropometric measurements revealed overall homogeneity of the three samples, closer similarity in the coastal region to adjacent North African populations, and Negroid influence in the Saharan Libyans. Anthropometry substantiated findings from blood markers.

Anthropological studies among Libyans. Erythrocyte genetic factors, serum haptoglobin phenotypes and anthropometry

Populations of Aswan governorate in Egypt have been studied with respect to blood, serum and enzyme groups as well as some other anthropological characters. One hemoglobin variant (Hb Khartoum) was de

Genetic Blood Markers and Anthropometry of the Populations in Aswan Governorate, Egypt

Hereditary Blood Factors and Anthropometry of the Inhabitants of the Egyptian Siwa Oasis

Three hundred and fifty-six Nubians of Upper Egypt were tested for hemoglobin variants and ABO blood groups. No hemoglobin variants were detected. ABO allele frequencies for the Konouz are: A 19.31, B 11.08, O 69.59; for the Arabs — A 22.02, B 9.64, O 68.33; and for the Fedikyaee—A 24.46, B 9.54, O 65.98.

K. Kamel

Papers

Genetic markers and anthropometry in the populations of the Egyptian oases of El-Kharga and El-Dakhla.

Anthropological studies among Libyans. Erythrocyte genetic factors, serum haptoglobin phenotypes and anthropometry

Genetic Blood Markers and Anthropometry of the Populations in Aswan Governorate, Egypt

Hereditary Blood Factors and Anthropometry of the Inhabitants of the Egyptian Siwa Oasis

Abo blood groups and hemoglobin variants among nubians, egypt, u.a.r.