Question

Understanding The Role Of Nucleosomes In Determining Chromatin Structure

Watch The Short Video In The Resources Folder Called “Dna Molecule: How Dna Is Packaged (Advanced)”. What Is The Role Of a Nucleosome In Determining Chromatin Structure? What Is One Thing About The Video That Sticks In Your Mind?

Name And Explain One Type Of Chemical Modification Of Histone Tails That Alters Chromatin Structure. Why Is That Important For Regulating Gene Expression?

Why Might a Cell Move Past The g1 Checkpoint In The Cell Cycle?

What Could Happen If a Cell Moves Past a Cell Cycle Checkpoint When It Shouldn’t?

ANSWER

The term autologous hematopoetic stem cells (HCTs) basically refers to the intravenous infusion of the hematopoetic stem and along with this the progenitor cells are also designed to rebuild the marrow and the immune function among the patients along with the problem of different types of malignant disorders. Moreover, it is also very crucial to mention that the patients who are already treated with chemotherapy or any other treatment measure, they are mainly treated with the HCTs in the hospital care setting. Therefore, in case of the autologous transplantation process the stem cells are usually derived from the bone marrow of the patient and it is generally collected from the peripheral blood (Lidonnici & Ferrari, 2018).

In case of the hemoglobinopathies it can be stated that the there are multiple types of genetic diseases that affect the humans of the different parts of the world. Therefore, in case of most of the hemoglobinopathies the use of the genetic treatments has become very popular in recent days. For example, the most common hemoglobinopathies are sickle cell anaemia and thalassemia. Such types of diseases are treated with the gene therapy protocols as well. According to the study of Snowden et al. (2018) it can be stated that the HCTs are widely used for treating the hemoglobinopathies disease by the health care professionals around the world. Therefore, in this study the researchers reported that the HCTs can also be used to treat the autoimmune diseases and in recent time, the use of HCTs indicates a better outcome for the treatments of the different autoimmune diseases. Hence, it can be stated that the gene therapy technique can easily be used to treat the different types of hemoglobinopathies.

In the selected article, the researchers mainly focused on the thalassemia as the haemoglobinopathy disease in their study to show the effectiveness of the gene therapy among the animal model. In this study the researchers reported about the use of the transgenic mice to investigate the beta-globin switching process among the human beings (McColl & Vadolas, 2016).

Chemical Modification Of Histone Tails

In this research, the researchers mainly used the gene deletion method for the disease of beta-thalasemia to identify the mutation process of various gene expressions among the mouse model. Mice homozygous for the mutation (Hbb^th-1) were feasible but required noticeable β^maj protein and exhibited sign of a compensatory upsurge in expression of the β^min gene in the body of the selected mouse models. Therefore, it can be stated that the hematological features were important of thalassemia intermedia in case of the homozygotes. On the other hand, heterozygotes displayed usual parameters of the blood. Therefore, the analysis of the Hbb^{t –}mouse showed that, compared to human, the lack of proteolytic degradation and reduced solubility of free mouse α-globin controlled the rigorousness of the Hbb^th-1 phenotype (McColl & Vadolas, 2016). However, it is also important to mention that the targeted alteration of that particular gene in the mice model by inserting the setectable neomycin cassette caused in a deadly thalassemia disease in homozygotes at later stage of gestation or in some cases just after birth.  In this case, the timing of the lethality among the mice is associated with the adult β-globin expression.  Moreover, the researchers also reported that the tangible phenotypic differences in between the Hbb^th-2 and Hbb^th-1 genes, that result from addition to the TK promoter’ locus within the targeting cassette (McColl & Vadolas, 2016).

In this specific study the researchers used the gene deletion technique for treating the disease conditions among the murine model of mice to assess the effectiveness of the gene therapy. Moreover, the present study the deletion of the mouse β-globin genes resulted in the process of beta thalassemia among the human model as well like the used mice model. Moreover, the research study also reported to use the splicing technique for rectifying the defects that led to the development of the Hbb^th-4 mouse. Moreover, the humanized models were also formed through the use of the bacterial recombineering methods to present definite β-thalassemia mutations into human genomic parts circulated as BACs, and the altered loci to produce transgenic animals (McColl & Vadolas, 2016).

No, the present study did not address the issue of the HSC transplant as the researchers used the gene deletion technique to address the issue. The study concluded that growth and obtainability of biological resources and refined genomic tools to use the mouse genome that has improved the understanding of the controlling network accountable for expression of the globin. The use of the mice model helped the researchers to understand the mammalian system. Therefore, the use of the mice model in the research may reduce the generalizability of the study to humans (McColl & Vadolas, 2016).

References

Lidonnici, M. R., & Ferrari, G. (2018). Gene therapy and gene editing strategies for hemoglobinopathies. Blood Cells, Molecules, and Diseases, 70, 87-101.

McColl, B., & Vadolas, J. (2016). Animal models of β-hemoglobinopathies: utility and limitations. Journal of blood medicine, 7, 263.

Snowden, J. A., Sharrack, B., Akil, M., Kiely, D. G., Lobo, A., Kazmi, M., … & Lindsay, J. O. (2018). Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases–a guide for the generalist. Clinical Medicine, 18(4), 329.

Autologous Hematopoietic Stem Cell Transplantation for Treating Hemoglobinopathies

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