# Sickle Cell Anemia

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According to what I read, the sickle cell anemia is caused by substitution of one nucleotide and it is common on Africa and Asia, especially to African people because of resistance to malaria.

I'm not sure I understood what that means. I'll add the quote from the book.

People who are heterozygous for sickle cell anemia ($H^A H^S$ are partially resistant to malaria, a serious disease that affects red blood cells. Sickle cell hemoglodbin is thought to offer this resistance because sickeled cells are frquently removed from the circulation and destroyed, killing any malaria parasites with them. People who are homozygous for normal hemoglobin $H^A H^A$, on the other hand, have no resistance to malaria.

Also, does this relate to the person's bloodtype also? Maybe this isn't too smart question but does the Landsteiner's bloodtype (which is just another name for common bloodtypes, A,B, AB, and O), influence to the person's bloodtype?

Thanks for the replies.

Happy Holidays

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Below is a quote from this site:

http://sickle.bwh.harvard.edu/malaria_sickle.html

You need to go to the site and look at the figures.

Figure 2 is a schematic of the natural selection that occurs with the gene for sickle hemoglobin in areas endemic for P. falciparum malaria. The left-hand side of the panel shows the situation in people with two genes encoding normal hemoglobin A (designated by red). These people have a significant chance of dying of acute malarial infection in childhood. In contrast, people with two genes for sickle hemoglobin (shown in green) are likely to succumb to sickle cell disease at an early age, as shown in the right-hand side of the figure.

In the center are people with sickle cell trait who possess one gene for normal hemoglobin and one gene for sickle hemoglobin. These children are more likely to survive their initial acute malarial attacks than are people with two genes for normal hemoglobin. Also, they suffer none of the morbidity and mortality of sickle cell disease. Therefore, the people with sickle cell trait are more likely to reach reproductive age and pass their genes on to the next generation (Ringelhann, et al., 1976).

The genetic selective scenario in which a heterozygote for two alleles of a gene has an advantage over either of the homozyous states is called "balanced polymorphism". A key concept to keep in mind is that the selection is for sickle cell trait. A common misstatement is that malaria selects for sickle cell disease. This is not true. A person with sickle cell disease is at an extreme survival disadvantage because of the ravages of the disease process. This means that a negative selection exists for sickle cell disease. Sickle cell trait is the genetic condition selected for in regions of endemic malaria. Sickle cell disease is a necessary consequence of the existence of the trait condition because of the genetics of reproduction.

The precise mechanism by which sickle cell trait imparts resistance to malaria is unknown. A number of factors likely are involved and contribute in varying degrees to the defense against malaria.

Red cells from people with sickle trait do not sickle to any significant degree at normal venous oxygen tension. Very low oxygen tensions will cause the cells to sickle, however. For example, extreme exercise at high altitude increases the number of sickled erythrocytes in venous blood samples from people with sickle cell trait (Martin, et al., 1989). Sickle trait red cells infected with the P. falciparum parasite deform, presumably because the parasite reduces the oxygen tension within the erythrocytes to very low levels as it carries out its metabolism. Deformation of sickle trait erythrocytes would mark these cells as abnormal and target them for destruction by phagocytes( Luzzatto, et al., 1970).

Experiments carried out in vitro with sickle trait red cells showed that under low oxygen tension, cells infected with P. falciparum parasites sickle much more readily than do uninfected cells (Roth Jr., et al., 1978). Since sickle cells are removed from the circulation and destroyed in the reticuloendothelial system, selective sickling of infected sickle trait red cells would reduce the parasite burden in people with sickle trait. These people would be more likely to survive acute malarial infections.

Other investigations suggest that malaria parasites could be damaged or killed directly in sickle trait red cells. P. falciparum parasites cultured in sickle trait red cells died when the cells were incubated at low oxygen tension (Friedman, 1978). In contrast, parasite health and growth were unimpeded in cells maintained at normal atmospheric oxygen tensions. The sickling process that occurs at low oxygen tensions was presumed to harm the parasite in some fashion. Ultrastructural studies showed extensive vacuole formation in P. falciparum parasites inhabiting sickle trait red cells that were incubated at low oxygen tension, suggesting metabolic damage to the parasites (Friedman, 1979). Prolonged states of hypoxia are not physiological, raising questions about degree to which these data can be extrapolated to human beings. However, they do suggest mechanisms by which sickle hemoglobin at the concentrations seen with sickle cell trait red cells could impair parasite proliferation.

Other investigations suggest that oxygen radical formation in sickle trait erythrocytes retards growth and even kills the P. falciparum parasite (Anastasi, 1984). Sickle trait red cells produce higher levels of the superoxide anion (O2-) and hydrogen peroxide (H2O2) than do normal erythrocytes. Each compound is toxic to a number of pathogens, including malarial parasites. Homozygous hemoglobin S red cells produce membrane associated hemin secondary to repeated formation of sickle hemoglobin polymers. This membrane-associated hemin can oxidize membrane lipids and proteins (Rank, et al., 1985). Sickle trait red cells normally produce little in the way of such products. If the infected sickle trait red cells form sickle polymer due to the low oxygen tension produced by parasite metabolism, the cells might generate enough hemin to damage the parasites (Orjih, et al., 1985).

The immune system is key to weathering attacks by P. falciparum. Maternal antibodies passed to newborns prior to birth provide some protection from malaria for the first several months of life. Thereafter, the onus is on the toddler's immune system to provide the needed defense. Epidemiological studies performed in regions with endemic malaria show that antibody titers to P. falciparum are lower in children with sickle cell trait than in children with genes only for hemoglobin A (Cornille-Brogger, et al., 1979). The investigators speculated that lower levels of immune activation might reflect a lower parasite burden in children with sickle cell trait due to clearance of the infected red cells. Analysis of people with sickle cell trait and people homozygous for hemoglobin A in the regions with endemic malaria in fact show a lower mean parasite burden in people with sickle cell trait relative to hemoglobin A homozygotes (Fleming, et al., 1979). In contrast, children with sickle cell disease have a high fatality rate, with acute malarial infections being a chief cause of death (Fleming, 1989).

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I'm kind of confused.

I'm just new to the biology in my high school so my class only got to the part about blood types A,B, O, AB with RH+ and RH-.

Can you translate that into the words I can read and understand? I really would appreciate it. I DID try to read it but it's just not easy

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Greyfalcon, resistance to malaria and SCA has nothing to do with the AB0 bloodtypes. Different bloodtypes simply mean different surface protein on the red blood cells. I'm not sure if this answers your question, because I'm not really sure if this was what you asked.

Also, does this relate to the person's bloodtype also? Maybe this isn't too smart question but does the Landsteiner's bloodtype (which is just another name for common bloodtypes, A,B, AB, and O), influence to the person's bloodtype?

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Oh, I see.

Thanks now. And I see why the bloodtype has no effect on it --> the SCA is caused by substitution of nucleotide of the polypeptide which doesn't matter on the person's bloodtype.

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According to what I read' date=' the sickle cell anemia is caused by substitution of one nucleotide and it is common on Africa and Asia, especially to African people because of resistance to malaria.

I'm not sure I understood what that means. I'll add the quote from the book.

Also, does this relate to the person's bloodtype also? Maybe this isn't too smart question but does the Landsteiner's bloodtype (which is just another name for common bloodtypes, A,B, AB, and O), influence to the person's bloodtype?

Thanks for the replies.

Happy Holidays[/quote']

http://forum.aidworkers.net/messages/141/141.html?1105057020

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