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Gene Isolation and Expression - Essay Example

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This essay "Gene Isolation and Expression" discusses the process in which the genes are expressed in the given cell. The gene expression level gives the most fundamental levels of diabetes…
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Gene Isolation and Expression
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Gene isolation and expression All the organisms have different types of cells each with some distinct functions and properties. The phenotype refers to the characteristic changes that occur in the cell. And the genotype refers to the functions of the genes with respect to the genetic code. They all have the same genome and they have genes. These genes are the region of coding present in all the cells. Gene expression is the process in which the genes are expressed in the given cell. All the genes are not expressed only a few genes are expressed. The result of the gene expression is the production of proteins of distinct types. If these gene expressions are modulated then the final product can also be changed. The translation, transcription, RNA splicing and post translational modification are the few processes that can be altered. This regulation gives control over the structure and function of the cell. The gene expression level gives the most fundamental levels of diabetes. Insulin is produced in the body by the islets of Langerhans cells. The islets of Langerhans constitute about 1-2% of the total volume of the pancreas. The beat cells that are present in the islets of Langerhans are responsible for the production of insulin. Their composition is heterogenous in nature. Insulin is used to convert the glucose molecule into energy. Insulin is the first hormone gene to be sequenced and characterized. The insulin gene provides an excellent model of gene expression in eukaryotes. The regulatory sequences of this gene are present very close. The expression of insulin in the body is due to the nutrient and hormonal simulations of the beta cell. Diabetes mellitus is the condition when our body is not able to convert the glucose into energy. Our body requires energy for the proper function. The conversion of glucose into energy is the most important pathway for energy in our body. If there is an increase in the level of the blood glucose then the occurrence of diabetes mellitus is possible. There are three types of diabetes mellitus. They are Type 1 Diabetes – this type of diabetes occurs in our body due to the destruction of the beta cells of the islets of Langerhans. It is also called as IDDM or Juvenile Diabetes. The major symptoms of T1D are poluria (frequent urination), poly phagia( increased hunger ), weight loss and poly dipsia ( increased thirst ). Injection of insulin in our body is the most common treatment. The concentration of insulin for injection will vary depending upon the condition of the person’s secretion level. This type of diabetes is more common among the children. (Barroso 2005). Type2 Diabetes – This type of diabetes mellitus is also called as non-insulin dependent and they are found to be more common among the adults. Hence it is called as adult- onset disease. The resistance to insulin develops in the body disabling the insulin activity. This type of diabetes can be brought under control to some extent by diet and exercise. Some problems associated with T2D are increased risk of heart attacks, amputation, kidney failure and sometimes hyperglycemia. It is also said that the T2D is mainly caused because of the lifestyle factors and genetics. The expression of the gene is promoted by the diet and exercise. (Krentz and Bailey 2005) .These cells are also fund to produce very less amount of insulin. The strong inheritable genetic connection with the disease makes some community more vulnerable to this disease. Similarly the same genetic inheritance allows the people to resist the diabetes mellitus II occurrence. The genetic variation is one of the most important causes for this disease. Gestational Diabetes – This is the condition where the women without any previous history of diabetes are found to have increased glucose level through out the pregnancy time. After child birth they are more likely to have diabetes also, the risk factor is 0.5 in this case. The main reason for this increase in glucose level is due to the hormones that are produced during the pregnancy period. Gestational diabetes affects the 3-10 % of the pregnancies. Type 2 Diabetes mellitus is a heterogeneous clinical entity that is found by the increase in the blood glucose level and due to the biological defects. The genetic inheritance is one of the most important factors of T2D.Many studies have concluded that the T2D is caused by the genes that are present in the chromosome 20. (Zhang C, 2006). (Saxena et al. 2006). The second factor is the life style. The food habits and the environment can also cause diabetes mellitus. Indians and Americans are much prone for diabetes. Similarly some groups of people at the southern region of Saudi Arabia are not prone for diabetes though they enjoy the same life style. Researches have concluded that four genes present at the chromosome 20 are responsible for the occurrence of diabetes mellitus in the human body. They are four genetic variants that are present in the chromosome 20 at the regulatory region of the gene hepatocyte nuclear factor 4 alpha. (HNF4A). This gene is an important transcription factor and regulates the expression of hundreds of genes. This gene acts as the master switch for the gene expression and regulation. It switches on the genes when necessary and turns off after the required metabolism has taken place. The HNF4A is present in the cells of liver and pancreas. They are also responsible for turning on the beta cells of Islets of Langerhans for the secretion of insulin on requirement. If there is a malfunction in the HNF4A gene then the entire mechanism may collapse. The insulin gene is not the target of HNF4A. HNF4A has the DNA binding specificities for the insulin gene. The L- pyruvate kinase and the glucose transporter 2 are the main targets of the HNF4A. The pyruvate kinase plays an important role in the glycolytic pathway and the glucose transporter 2 encodes the glucose transporter that is present in the liver and pancreas. Thus it is concluded that HNF4A plays an important role in the T2D. (Burris and McCabe 2001). The four genetic variants that are present near the HNF4A region and found to have great impact on the T2D are hepatocyte nuclear factor 4 alpha. ( HNF4A). In order to study about the importance of these genetic variants on the gene HNF4A , the non parametric multifactor dimensionality reduction and modified and generalized MDR were used. (Alsmadi et al. 2008). These four genes varied based on a single nucleotide. Hence single nucleotide polymorphism studies were used to find the effect of these SNPs on the HNF4A gene regulation. The logistic regression level was also found from the experiments. The biological and mechanical effects of these genetic variants were studied by a group of scientists. When SNP was used for genotyping, it was found that the gene TCF7L2 was found to have greater significance for the gene regulation of HNF4A. The scientists have also found that TCF7L2 is the only universal gene having association with T2D. The variation in this gene is found to impair the production of insulin secretion and increase the body glucose level. People carrying this variant in their body at the active state are much prone for diabetes then other people. The functions of TCF7L2 are cell proliferation, adipogenesis, myogenesis and pancreatic islet development. This gene also activates the genes coding for the intestinal proglucagon and glucagons like peptides 1 and 2. The next most important gene associated with these SLC30A8, which is a zinc transporting gene that is found to make the zinc available for the co crystallization and secretion of insulin. Similarly PPARy is another gene that is found to control the expression level of the several genes and affects the insulin sensitivity. PPARy agonist is found to increase the adipose tissue of the body and reduce the triglyceride levels and increase the insulin sensitivity. (Burris and McCabe 2001). If more than 10 variants are present in the chromosome 20, then that particular person is found to have increased risk for diabetes mellitus. The P12A allele was one thought to play some role in the T2D, but later it was found that they have no association with the type II diabetes. This was confirmed by a German study of Ringel et al. (Burris and McCabe 2001). The Wu et al. (2009) team have found that of the six genotyped SNPs adiponectin, C1Q and collagen domain containing (ADIPOQ), ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1), growth hormone secretagogue receptor (GHSR), peroxisome proliferator-activated receptor gamma (PPARγ) and transcription factor 7-like 2 (TCF7L2), ENPPI and GHSR are found to be more associated with the diabetic neuropathy. The techniques used by them are logistic regression analysis model and generalized multi factor dimensionality reduction. Many studies have found that two intronic SNPs rs12255372 and rs7903146 are found to be associated with the T2D. These intronic SNPs effect on the T2D was understood through the genotyping. Similarly another intronic SNP rs1884613 is found to have greater effect on the HNF4A than the other introns. They don’t have any specific function. Similarly the KCNJ11 situated on the chromosome 11p15.1 is found to regulate glucose induced insulin secretion in the pancreatic cells. These genes are found to encode for the Beta –cell ATP sensitive potassium channel. The mutations occurring in this region has resulted in the ketoacidosis and hyperglycemia. Though mutations in this gene are very rare, they also contribute to the T2D occurrence heavily. The occurrence of the Diabetes mellitus 2 in the saudi arabian population is very less because of the presence of the gene E23K. This gene prevents them from the occurrence of T2D. The presence of the octomeric structure of the KATP channel transfers the glucose – mediated metabolic signals into electrical signal for insulin induction. Conclusion: The saudi arabian people have the genes that are not susceptible for the diabetes mellitus in their body. E23K is the most important gene for the continuous insulin secretion. Whereas the people of other origin are having the T2D susceptible genes which when mutated or mis lead will cause stop insulin production. Instead of the susceptible gene , they have the well performing inducing gene. This is the main reason why the sothern regions of Saudi Arabia enjoy a T2D free life. References: Alsmadi, O, Al-Rubeaan, K, Wakil, SM, Imtiaz, F, Mohamed, G, Al-Saud, H, Al-Saud, NA, Aldaghri, N, Mohammad, S and Meyer, BF. “Genetic study of Saudi diabetes (GSSD): significant association of the KCNJ11 E23K polymorphism with type 2 diabetes”, Diabetes/Metabolism Research and Reviews, vol. 24, no. 2, pp.137- 40. Barroso, I 2005, Genetics of Type 2 diabetes, Diabetic Medicine, vol. 22, no. 5, pp. 517–535. Burris, TP and McCabe, ERB 2001, Nuclear receptors and genetic disease, Academic press. Krentz, AJ and Bailey, CJ 2005, Type 2 Diabetes in practice, RSM Press. Saxena, R, Gianniny, L, Burtt, NP, Lyssenko, V, Giuducci, C, Sjogren, M, Florez, JC, Almgren, P, Isomaa, B, Orho-Melander, M, Lindblad, U, Daly, MJ, Tuomi, T, Hirschhorn, JN, Ardlie, KG, Groop, LC and Altshuler, D. “Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals”, Diabetes, vol. 55, pp. 2890–2895. Zhang, C, Qi, L, Hunter, DJ, Meigs, JB, Manson, JE, van Dam, RM and Hu, FB. “Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of U.S. women and men”, Diabetes, vol. 55, pp. 2645–2668. Wu, LS, Hsieh, CH, Pei, D, Hung, YJ, Kuo, SW and Eugene Lin, 2009, Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARγ and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes, Nephrology Dialysis Transplantation, vol. 24, no.11, pp. 3360-3366. Read More
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