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[object Object],Abstract<br />Hemoglobin is a protein found in humans and various other organisms. In most organisms it is present in, its primary function which is transport of oxygen in blood is similar. Sickle cell disease is a result of the mutation of hemoglobin B (a form of hemoglobin protein). We hypothesize that if hemoglobin B is conserved within animals, then they can possibly develop sickle cell anemia. This hypothesis was explored in by analyzing several Old and New World organisms with the BLAST, Muscle and Phylip databases. We generated phylogenetic trees and found that chimpanzees and orangutans were most closely related to humans. We also found no evidence suggesting that mutation of the hemoglobin B protein in them led to Sickle Cell Anemia.<br />Introduction<br />Hemoglobin is a protein encapsulated in red blood cells (Shechter, 2008). It’s primary function is the transportation of oxygen in blood not only in humans but various organisms in which hemoglobin is also present (Remington, et al 2008). A mutation of hemoglobin B which is a form of the hemoglobin protein in which the red blood cell becomes sickle shaped results in a disease called Sickle Cell disease. In-depth research has been done on this disease as it is rampant amongst many human populations. Some symptoms of the disease include difficulty in breathing, dizziness and pain among others in humans (Browning, et al 2006). As hemoglobin is present in other organisms and has similar functions in them, Team International decided to do research and find out whether mutation of the protein would result in sickle cell disease as well. We hypothesize that if hemoglobin B is conserved within animals, then they can possibly develop sickle cell anemia.<br />Methods and Results<br />                                         +------HBG2-Night                                  +-31.4-|                          +-87.4-|       +------HBG2-Squir                          |       |          +---------100.0-|       +--------------HBG2-Capuc          |               |          |               +----------------------HBG2-Marmo          |  +-100.0-|                       +--------------HBG2-Orang  |       |               +-78.5-|  |       |               |       |       +------HBG2-Human  |       |       +-29.5-|       +-84.8-|  |       |       |       |               +------HBG2-Chimp  |       +-90.2-|       |  |               |       +----------------------HBG2-Rhesu  |               |  |               +------------------------------HBG2-Baboo  |  +----------------------------------------------HBG2-HorseWe obtained the FASTA sequence of Hemoglobin B (hereinafter referred to as HBG2) using the Entrez Gene database. We then ran a psiBLAST on it. Although most of the BLAST results retrieved were from Homo sapiens, there were also others from some primate species including a near perfect match to a protein cloned from a Sumatran Orangutan’s blood sample and the common chimpanzee. Using the BLAST results, we retrieved the HBG2-similar FASTA sequences of Common Chimpanzee (Pan troglodytes), Sumatran Orangutan (Pongo abelii), Rhesus Macaque (Macaca mulatta), Olive Baboon (Papio anubis), Common Marmoset (Callithrix jacchus), Tufted Capuchin (Cebus apella), Common Squirrel Monkey (Saimiri sciureus), Nancy Ma's Night Monkey (Aotus nancymaae), and Horse (Equus caballus). In order to find out whether human HBG2 sequences are similar to Old or New World Primates, the organisms were specifically chosen as the first four are Old World primates, the horse was used as an outgroup and the other are New World primates. Finally, the sequences were analyzed with Phylip using Muscle. The following phylogenetic trees were generated:<br />a.)<br />                                         +------HBG2-Night                                  +-31.4-|                          +-87.4-|       +------HBG2-Squir                          |       |          +---------100.0-|       +--------------HBG2-Capuc          |               |          |               +----------------------HBG2-Marmo          |  +-100.0-|                       +--------------HBG2-Orang  |       |               +-78.5-|  |       |               |       |       +------HBG2-Human  |       |       +-29.5-|       +-84.8-|  |       |       |       |               +------HBG2-Chimp  |       +-90.2-|       |  |               |       +----------------------HBG2-Rhesu  |               |  |               +------------------------------HBG2-Baboo  |  +----------------------------------------------HBG2-Horseb.)<br />Figure 1 – Phylogenetic tree depicting relationship between old and new world primate hemoglobin B protein sequence.<br />Discussion<br />In this project we tried to examine the HBB2 gene to see whether all the species having this gene are susceptible to contain the Sickle Cell Anemia mutation. At first we started searching for  the species having this gene which are Common Chimpanzee (Pan troglodytes), Sumatran Orangutan (Pongo abelii), Rhesus Macaque (Macaca mulatta), Olive Baboon (Papio anubis), Common Marmoset (Callithrix jacchus), Tufted Capuchin (Cebus apella), Common Squirrel Monkey (Saimiri sciureus), and Nancy Ma's Night Monkey (Aotus nancymaae). In order to find out this we selected two main species which are closely related to Homo sapiens they are Common Chimpanzee (Pan troglodytes), Sumatran Orangutan (Pongo abelii). We tried searching for any literature pertaining to these animals naturally acquiring Sickle Cell, but no relevant studies appeared, not even for any primate. <br />Conclusion<br />We tried to explore the properties and functionality of hbb2 in some primate species, like chimpanzees, orangutans, macaques, baboons, and squirrel monkeys, as these are found to have the gene sequences similar to that of human species. We came to know these similarities from the  phylogenetic trees which were retrieved using Philyp through MUSCLE.As a part of our work we compared new world and old world primates to see if either of them would have HBB2 sequences similar to humans.. Among all these species chimpanzees and orangutans were closely related. So, we started exploring the HBB2 sequences in similarly related animals using PubMed and Google scholar databases but could only retrieve limited results for chimpanzees being artificially injected with blood from a sickle-cell patient. From what we found, we do not think that animals other than humans can naturally acquire Sickle Cell Anemia, in contrary to our hypothesis. Further research may, however, see whether primates other than humans can acquire sickle cell anemia by examining their hemoglobin genes and seeing whether it is genetically possible for primates to acquire Sickle Cell Anemia.<br />References<br />,[object Object]
Shechter, A.N. 2008. Hemoglobin Research and The Origins of Molecular Medicine.  The American Society of Hematology. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581994/?tool=pmcentrez
Browning, J.A.,  Staines, H.M., Robinson, H.C., Powell, T., Elory, J.C., and Gibson, J.S. 2006. The Effect Of Deeoxygenation On Whole-cell Conductance Of Red Blood Cells From Healthy Individuals and Patients With Sickle Cell Disease. Blood. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951509/?tool=pmcentrez
Sara Gardenghi,1 Pedro Ramos,1,2 Maria Franca Marongiu,1 Luca Melchiori,1 Laura Breda,1 J Clin Invest. 2010 December 1; 120(12): 4466–4477.
Hemoglobin B Mutation and Sickle Cell Disease

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Hemoglobin B Mutation and Sickle Cell Disease

  • 1.
  • 2. Shechter, A.N. 2008. Hemoglobin Research and The Origins of Molecular Medicine. The American Society of Hematology. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581994/?tool=pmcentrez
  • 3. Browning, J.A., Staines, H.M., Robinson, H.C., Powell, T., Elory, J.C., and Gibson, J.S. 2006. The Effect Of Deeoxygenation On Whole-cell Conductance Of Red Blood Cells From Healthy Individuals and Patients With Sickle Cell Disease. Blood. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951509/?tool=pmcentrez
  • 4. Sara Gardenghi,1 Pedro Ramos,1,2 Maria Franca Marongiu,1 Luca Melchiori,1 Laura Breda,1 J Clin Invest. 2010 December 1; 120(12): 4466–4477.