SICKLE CELL : HAEMOGLOBIN GENETICS
Normal haemoglobin is called hemoglobin A but people with sickle cell disease have only hemoglobin S which turns normal, round red blood cells into abnormally curved (sickle) shapes. Normally, a person inherits two, copies of the gene that produces beta globin, a protein needed to produce normal hemoglobin (hemoglobin A, genotype AA). A person with sickle cell trait inherits one normal gene and one abnormal gene encoding hemoglobin S (hemoglobin genotype AS).
INDEPENDENT ORIGINS OF THE SICKLE CELL GENE.
HAEMOGLOBIN GENETICS: Two mutations found in non transcribed sequences of DNA adjacent to the B-globin gene are so close to each other that the likelihood of crossover is very small. Restriction endonuclease digests of the B-globin gene cluster have shown five distinct patterns associated with sickle cell (CAG-GTG) mutation (Almeida and Roberts, 2005).
Four are observed in Africa, the Bantu, Benin, Sengal and Cameroon types and a fifth type is found in the Indian subcontinent and Arabia. The cited authors repot that haplotype analysis in the B-globin region shows strong linkage disequilibrium over the distance indicated which shows that Hbs mutation occurred independently at least five times. The high level of AS in parts of Africa and India presumably resulted from independent selection occurring in different populations living in malarious environments.
The demonstration that sickle cell heterozygoten have some degree of protection against P. falciparum was the first example of genetically controlled innate resistance to human malaria as recognized by experts on inherited factors affecting human infectious diseases (Alcais, et al, 2009). It was also the first demonstration of Darwinian selection in humans as recognized by evolutionary biologists (carrol, 2009).
DISTRIBUTION OF THE SICKLE CELL GENE (HAEMOGLOBIN GENETICS)
Since sickle cell homozygotes are at a strong selective disadvantage, while protection against malaria favours the heterozygotes, it would be expected that high frequencies of the Hbs gene would be found only in populations living in regions where malaria transmission is intense. Frequencies of sickle cell heterozygotes are 20-49% in malarious areas, whereas they are very low in the highlands of Kenya, Uganda and Tanzania.
High frequencies of the Hbs gene are confined to a broad belt across central Africa, but excluding most of Ethiopia and the East African highlands, this corresponds closely to areas of malaria transmission. Sickle cell heterozygote frequencies up to 20% also occur in pockets of India and Greece that were formerly high Malarious. Thousands of individuals have been studied, and high frequencies of abnormal hemoglobins have not been found in any population that was malaria free.
PREVALENCE OF SICKLE CELL TRAIT
Sickle cell trait is highest in West Africa (25% of the population). It also has a high prevalence rate in South and Central Americans, especially in panama. However, it also very infrequently appears in Mediterranean countries such as Italy, Greece and Spain, where it most likely expanded via the selective pressure of malaria, a disease that was endemic to the region. It has been described in Indians, Middle Easterners (such as Arabs and Iranians), Native American people, North Africans and Turks.
Due to the adaptive advantage of the heterozygote, the disease is still prevalent, especially among people with recent ancestry in malaria stricken areas such as Africa, the Mediterranean, India and the Middle Eas.
Malaria was historically endemic to Southern Europe, but it was declared eradicated in the mid-20th century, with the exception of rare sporadic cases. The malaria parasite has a complex life cycle and spends part of it in red blood cells. In a carrier, the presence of malaria parasite causes the red blood cells with defective hemoglobin to rupture prematurely making the plasmodium unable to reproduce. The polymerization of Hb effects the ability of the parasite to digest Hb in the first place. Therefore, in areas where malaria is a problem, people’s chance of survival actually increase if they carry sickle cell trait.
In the USA, where there is no endemic malaria, the prevalence of sickle cell anaemia among blacks is lower (about 0.25%) than in West Africa (about 4.0%) and is falling. Without endemic malaria, the sickle cell mutation is purely disadvantageous and will tend to be selected out of the affected population.
However, the so called African American community of the USA is known to be the result of significant admixture between several African and non-African ethnic groups and also represents the descendants of survivors of the slavery and the slave trade.
Thus, a lower degree of endogamy and particularly, abnormally high health selective pressure through slavery may be the most plausible explanations for the lower prevalence of sickle cell anaemia among Afro-Americans compared to sub-saharan African people. Another factor limiting the spread of sickle cell genes in North America is the absence of cultural proclivities to polygamy, which allows affected males to continue to seek unaffected children with multiple partnern.