Harman
Singh
Genetic
Disorders
Sickle
Cell Anemia
Sickle Cell Anemia
is a codominent genetic disorder stemming from the 11th pair of
chromosomes which affects the hemoglobin of red blood cells. The phenotypic
expression of the disease is sickled cells, which are red blood cells that are
rigid, and sticky, and shaped like crescent moons. Sickled cells have a shorter
lifespan, dying quicker than they resynthesize in the bone marrow. As a result,
fewer red blood cells exist at any time versus if the individual did not have
the disease; this condition is known as anemia.
The symptoms of
the disease include fatigue, shortness of breath, dizziness, coldness in hands
and feet, and jaundice (yellowing of the skin). Sudden pain throughout the
body, known as a sickle cell crisis, is also common among individuals with the
disease. Sickle cell crises occur when sickled cells block blood passage
through the capillaries of the body. Since less oxygen is able to be absorbed
by sickled red blood cells, less oxygen is being transferred to the cells
throughout one’s body. The long term effect of reduced oxygen efficiency as
well as damaged capillaries and organs when the sickled red blood cells pass
through shortens ones lifespan. The estimated life span of individuals with the
disease is from 50 to 60 years. Death in individuals with the disease come from
acute pains caused by sickle crises followed by a stroke or heart attack.
The disease is
caused by a mutated version of the gene that produces one part of the hemoglobin
protein, the gene creating the beta hemoglobin peptide chain. The hemoglobin
protein is formed when the alpha hemoglobin peptide chain and the beta hemoglobin
peptide chain connect to each other through hydrogen bonds, ionic bonding, and
disulfide bonds between the sulfur atoms of cysteine in each chain. The most
important type of bonding between these chains for sickle cell anemia is the
hydrophobic effect, where hydrophobic regions of the chains move toward the
center of the protein and away from the water. The alpha and beta chains are
also called the beta globin chains and the alpha globin chains.
The exact mutation
in the beta globin chain is the replacing of glutamic acid with valine at the
sixth position of the chain, when the beta globin chain is synthesized. Valine
is less polar than glutamic acid, and causes the hydrophobic effect to kick in.
The hemoglobin’s altered shape causes it to become less soluble when there are
decreasing oxygen concentrations, such as when oxygen is deposited to other cells
in the body. The hemoglobin clumps together instead of remaining apart and dissolving
in the blood plasma. These clumped hemoglobin regions polymerize into crystals,
which elongate the red blood cells into a crescent moon shape.
How does it occur? The alleles for the disease
are inherited from the parents thorough their chromosomes, and the chromosomes
are the complexes of the DNA which codes for beta globin. The DNA produces
mRNA, which uses codons, tRNA, and ribosomes to precisely place the amino acid
sequence of beta globin together. In this way, an organism’s inheritance of
alleles from its parents affects its DNA, its synthesis of proteins, and its
phenotypic expression of whether they have sickle cell anemia or not.
On the 11th
pair of chromosomes, the 2 alleles of the gene that produces the beta globin
are (Hb A), and (HB S). A normal individual inherits an (Hb A) allele from both
parents, causing the gene to produce normal beta globin. An affected individual
who shows the symptoms of sickle cell anemia must have inherited (HB S) from
both their parents. A heterozygous individual who has both (Hb A) and (HB S)
alleles produce both sickle red blood cells and normal red blood cells; the
alleles are codominant and both are fully expressed. However, the heterozygous
individual rarely shows any symptoms because the normal red blood cells they
produce can carry on most of the regular functions. In this way, the phenotype expression
for blood synthesis is codominant but the phenotype expression for the disease is
autosomal recessive. In addition, the
heterozygous individual is a carrier for the sickle cell disease, and with the
use of punnet squares, one can find the probability of whether the individual
and their mate will have a child affected by the disease.
Since this is not
a sex-linked disease, males and females are equally affected by the disease.
Africans and African-Americans are most at risk of having sickle cell anemia.
This is because individuals with sickle cell anemia are resistant to malaria
since malaria cannot spread in sickled blood cells, and evolution has allowed
people with African descent to obtain this trait in their blood. Individuals
with Middle Eastern, South Asian, or South-Eastern European descent are also
more likely to have the disease because mosquitoes carrying malaria also exist
in those regions.
In Canada, as soon as the child is born, the blood used for other tests is also used to test for sickled red blood cells. A hemoglobin concentration test is done, and if the concentration is lower than normal for the newborn, the newborn is diagnosed with anemia. Further tests are done on the newborn to pinpoint the reason for the low hemoglobin count, such as the high-performance liquid chromatography test, which identifies the type of hemoglobin present. Parents also may want to genetically screen themselves by taking blood tests to check if they are carriers of the disease before having a child. Since carriers also produce sickled cells since it is a codominant disease, a high-performance liquid chromatography test can identify whether the parents are carriers as well. If individuals were not diagnosed with the disease when they were born, then they should visit their doctors to receive appropriate blood tests if they show the symptoms described earlier.
A cure does not exist at this time, but there are treatments that help to manage and control the symptoms and limit the number of sickle cell crises. The treatment is continuous even when the individual does not show symptoms to keep them from appearing. Treatment for mild pain includes Tylenol or nonsteroidal anti-inflammatory drugs. Opioids are used for severe pain. Regular trips to the hospital for hydration, oxygen therapy and blood transfusions may also be required for the treatment of acute versions of the disorder. The blood transfusions try to increase the oxygen carrying red blood cells and decrease the concentration of sickle cells. The most hopeful, effective, and widely used treatment is Hydroxyurea. Hydroxyurea, a pill that can be taken orally, changes the mechanism of blood synthesis, causing the body to synthesize fetal hemoglobin rather than the abnormal hemoglobin. Fetal hemoglobin is the type of hemoglobin newborns have. Since the body is now biosynthesizing a different hemoglobin, the production of abnormal red blood cells is reduced as the body puts resources into synthesizing the other type. With Hydroxyurea, individuals with the disease can lead normal lives.
Some people opt out of having routine blood transfusions due to the ethical issues concerned with having someone else’s blood in one’s body. Jehovah’s witnesses especially have deep religious convictions, and are against the idea of blood transfusions since it “spoils” the person’s blood. Other than blood transfusions, treatments such as Hydroxyurea or penicillin do not present ethical issues since they are just pills that can be taken orally.
In my opinion, I feel more research needs to be done into stem cells, and their use in creating artificial organs. Particularly, I believe the disorder can be cured by replacing the organ that makes blood: the bone marrow. Not all of the bone marrow needs to be replaced either - heterozygotes of the disease carry both good blood and bad blood, and they rarely experience any symptoms. So individuals who produce only sickled cells can live normal lives if they replace some of their bone marrow and begin to produce healthy red blood cells. I feel further research needs to be done with the creation of such organs. Also the decision of which bone marrows should be replaced is important since there are many of them in the human body and some produce more blood than others. Finally, will the new bone marrows be compatible with the individual since two of the alleles on the 11th chromosome were changed? What do you think?
References
http://www.news-medical.net/health/Sickle-Cell-Disease-Genetics.aspx
I feel that the new bone marrow will be compatible with the two alleles on the 11th chromosome as long as the patient is receiving marrow from a donor with the same marrow because if its not a match wouldn't the marrow be seen as a virus and be rejected.-Wiam
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