Sickle-cell disease

Sickle-cell disease is a genetic disorder in which red blood cells may change shape under certain circumstances. This causes the cells to become stuck in capillaries which deprives the downstream tissues of oxygen and causes ischemia and infarction. The disease usually occurs in periodic painful attacks, eventually leading to damage of internal organs, stroke, or anemia, and usually resulting in decreased lifespan. It is common in people from countries with a high incidence of malaria, and especially in West Africa, or in descendents from those people.

Genetics

The allele responsible for sickle cell anaemia is autosomal recessive. A person who receives the defective gene from both father and mother develops the disease; a person who receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a carrier. If two parents who are carriers have a child, there is a 1-in-4 chance of their child developing the illness and a 1-in-2 chance of their child just being a carrier.

Related Topics:
Allele - Autosomal recessive - Carrier

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The gene defect is a known mutation of a single nucleotide (A to U) of the β-globin gene, which results in glutamic acid to be substituted for valine at position 6. Hemoglobins with this mutation are referred to as HbS, as opposed to the more normal adult HbA. The genetic disorder is due to the mutation of a single nucleotide, to a GAG to GTG codon mutation. This is normally a benign mutation, causing no apparent effects on the secondary, tertiary, or quaternary structure of hemoglobin. What it does allow for, under conditions of low oxygen concentration, is the polymerization of the HbS itself. In people heterozygous for HbS (carriers of sickling hemoglobin), the polymerization problems are minor. In people homozygous for HbS, the presence of long chain polymers of HbS distort the shape of the red blood cell, from a smooth doughnut-like shape to ragged and full of spikes, making it fragile and susceptible to breaking within capillaries. Carriers only have symptoms if they are deprived of oxygen (for example, while climbing a mountain) or while severely dehydrated. For those afflicted with the disease, however, vasocclusive events can be a painful part of life (normally they occur 0.8 times per year per patient). The occurs when HbS becomes deoxygenated it undergoes an abnormal change in shape and consistency which can lead to a change in the shape and plasticity in the cell wall of the RBC, an occurrence called sickling.

Related Topics:
Mutation - Nucleotide - Glutamic acid - Valine - Hemoglobin - Codon - Secondary - Tertiary - Quaternary - Oxygen - Polymerization - Heterozygous - Homozygous - Doughnut - Capillaries - Dehydrated

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The sufferers of the illness have a reduced life span. It is believed that carriers (sickle cell trait) are relatively resistant to malaria. Since the gene is incompletely recessive, carriers have a few sickle red blood cells at all times, not enough to cause symptoms, but enough to give resistance to malaria. Because of this, heterozygotes have a higher fitness than either of the homozyogotes. This is known as heterozygote advantage.

Related Topics:
Malaria - Fitness - Heterozygote advantage

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The malaria parasite has a complex life cycle and spends part of it in red blood cells. In a carrier, the presence of the malaria parasite causes the red blood cell to rupture, making the plasmodium unable to reproduce. Further, the polymerization of Hb affects the ability of the parasite to digest Hb in the first place. Therefore, in areas where malaria is a problem, people's chances of survival actually increase if they carry sickle cell anaemia.

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Due to the above phenomenon, the illness is still prevalent, especially among people with recent ancestry in malaria-striken areas, such as Africa, the Mediterranean, India and the Middle East. In fact, sickle-cell anaemia is the most common genetic disorder among African Americans; about 1 in every 12 is a carrier.

Related Topics:
Africa - Mediterranean - India - Middle East

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The evolution of sickle-cell anaemia is probably an example of Baldwinian evolution, whereby humans modify their environment and thus change the selective pressures. As humans in tropical areas in Africa and elsewhere developed agriculture and animal husbandry, they expanded the niche for Anopheles mosquitoes that could transmit the malaria parasite.

Related Topics:
Baldwinian evolution - Anopheles

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It is interesting that in the USA, where there is no endemic malaria, the incident of sickle cell anaemia amongst people of African descent is much lower than in West Africa and falling. Without endemic malaria from Africa, the condition is purely disadvantageous, and will tend to be bred out of the affected population.

Related Topics:
USA - African - West Africa

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See the Price equation article for a simplified mathematical model of the genetic evolution of sickle cell anemia.

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