Sickle cell anaemia is a severe disease biology essay

Sickle cell anaemia is inherited in an autosomal recessive pattern. It is inherited according to Mendelian model. This means that both copies of the gene in every cell oppose mutations. An autosomal recessive’s parents denote a condition where each of them carries one copy of the mutated gene, but they are not showing any signs and symptoms of the conditions. Unfortunately, they can still pass the defective genes to their children. Their offspring have a 25% chance of having homozygous sickle genotype or a having homozygous normal genotype. Besides, heterozygous superiority is the reason why the allele of the disease is said to be persistence. Although the disease is not showing up in every generation but it is kept in the gene pool without disappearing. Hardy-Weinberg principle have told us that, unless specific disturbing influenced are introduced, allele and the frequency of genotype in a population will remain the same and they are in equilibrium generation after generation. The disturbing influences include mutations, limited population size, selection, non-random mating, random genetic drift, gene flow, meiotic drive and ” overlapping generations”. So, as long as the heterozygous and the homozygous recessive condition do not disturb mating probabilities, the allele will naturally persist in the population. Malaria is commonly known as the ” mosquito disease” can be assumed as inborn to the sub-African region in Africa and is one of the most common causes of death. When introduced to Malaria, those who are the carrier of the sickle cell disease, which has the sickle cell traits, do not contract with the malaria disease. Carrying two copies of sickle cells alleles is disadvantageous; however carrying only one copy is advantageous if you are living in any area, which malaria is usual. The allele is beneficial as it shows resistance to malaria. And this is said to be the heterozygous advantage. Sickle cell anemia is causing by the genetic mutation. There are many diseases that are associated with mutations and negative implication is kind of a common thing for mutations. By a small alteration in only one of the three billions A’s, T’s, C’s and G’s, it can lead to the sickle cell anaemia, which is one of the life-threatening disease. Sickle cell anaemia is the result of a modification in a single nucleotide and denotes just one class of mutations called point mutation. Hemoglobin of an adult consists of two alpha-globin chains and two beta-globin chains. The gene for beta hemoglobin in sickle cell anaemia is mutated. Beta hemoglobin is a single chain of 147 amino acids. As the single-base mutation only involve the sixth amino acid in the chain substituting from glutamic acid (GAG) to valine (GTG), the resulting protein still comprises of 147 amino acids. At a DNA level, this is due to the substitution of a single base, from adenine (A) to thymine (T) at the sixth codon. An extremely drop in the solubility of sickle cell hemoglobin when deoxygenated is triggered by the substitution. The alteration of the electrophoretic mobility is the result for losing of negativity charged of glutamic acid. The problem arises when oxygen dissociates from hemoglobin. The substitutions of adenine to thymine, which result to the production of the amino acid valine, also lead to the synthesis of abnormal hemoglobin, which is called hemoglobin S. The conformation changes of the deoxygenated hemoglobin molecule results the valine to stick to a hydrophobic area on a neighboring molecule. This rapidly leads to stacking of the abnormal versions of the hemoglobin into a long polymer that distorts the cell membrane into its characteristics, sickle cell. Hemoglobin S tends to crystallize (sickle), deforming red cells into a crescent (sickle) shape and cause red blood cells to destruction by the spleen, even in a normal condition. The sickle-shaped cell can build up in capillaries and veins may disturb the blood flow and associate with fragility in rapid red blood cell destruction that leads to anaemia. The deformation of the sickle cell shape makes them difficult to pass through any small blood vessels and can lead to the blockage of the small vessels. Sometimes, serious medical complications can be caused by the inflexible and sickle-shaped cells, which stuck in small blood vessels. As far from that, an individual who is a carrier of sickle cell anaemia, which in other words a person who is heterozygous, they will not show any clinical abnormalities. Heterozygous is referring to a condition where an allele is dominant and the other one allele is recessive. Logically, any phenotypic changes are influenced by the dominant allele. In the case of the sickle cell disease, the allele of sickle cell is recessive while the allele for normal cell is dominant. Hence, that is why the disease is not expressed to the carrier of the disease. Although the person is not infected with the disease but still they have the sickle cell trait. Normally, there will be no consequences happen. But, in certain condition where there are short of oxygen, the person may temporarily suffered. The trait may shows up when the person with the sickle cell trait having a dynamic exercise or in a high-pitched altitude. In order to combat against the sickle cell anaemia, which is one of the life-threatening disease there are few strategies have been discovered. Present trials focus on production of fetal hemoglobin to obstruct polymer formation, treatment and prevention of infections, analgesic measures to control pain, and surgical treatment complications. The only offered cure is allogeneic bone marrow transplant. Blood and marrow stem cell transplant is able to work well to cure sickle cell anemia. However, the transplant procedure only manages to cure a small group of people. Besides the fussiness of the procedure itself, which usually the stem cell used for the transplant is needed from a close family member who is free form the sickle cell disease, the blood and marrow stem cell transplant also is so risky and perhaps can lead to side effects and even can cause death. And commonly the transplant procedure is used to treat young people who are still in a severe case. Latest, the uses of viral vectors are the most effective tools accessible. The options for the gene delivery vectors include the gamma-retroviruses, which known as C-type murine retrovirus or oncoretrovirus, the spumaviruses, which known as foamy viruses and the lentivirus that are from the retroviridae family. Among the three genera, the most efficient gene delivery vector is the lentiviral. Lentiviral is use as a vector for globin gene transfer to bone marrow and results in the correction of sickle cell anemia. A gene therapy protocol that alters the disease in animal model then straight transfers to human patients is developed critically. A least amount of self-inactivating (SIN) lentiviral vector comprising a vigorous anti-sickling beta-globin gene is designated as an unmobilized and highly purified bone marrow stem cells method. Levasseur et al have managed to correct their mouse model of sickle cell disease by using a minimum amount of SIN lentiviral-based vector aimed to provide an ant sickling human beta-globin gene into purified hematopoietic stem cell (HSCs). More potent anti sickling activity and a greater affinity for alpha-globin are also engineered by them.