Concepts of Genetics (12th Edition)
Concepts of Genetics (12th Edition)
12th Edition
ISBN: 9780134604718
Author: William S. Klug, Michael R. Cummings, Charlotte A. Spencer, Michael A. Palladino, Darrell Killian
Publisher: PEARSON
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Chapter 17, Problem 24ESP

A particular type of anemia in humans, called β-thalassemia, results from a severe reduction or absence of the normal β-globin chain of hemoglobin. However, the γ-globin chain, normally only expressed during fetal development, can functionally substitute for β-globin. A variety of studies have explored the use of the nucleoside 5-azacytidine for the expression of γ-globin in adult patients with β-thalassemia.

  1. (a) How might 5-azacytidine lead to expression of γ-globin in adult patients?
  2. (b) Explain why this drug may also have some adverse side effects.
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A particular type of anemia in humans, called b-thalassemia,results from a severe reduction or absence of the normal b-globinchain of hemoglobin. However, the g@globin chain, normally onlyexpressed during fetal development, can functionally substitutefor b-globin. A variety of studies have explored the use of thenucleoside 5-azacytidine for the expression of g-globin in adultpatients with b-thalassemia.(a) How might 5-azacytidine lead to expression of g-globin inadult patients?(b) Explain why this drug may also have some adverse side effects.
The proximal histidine residues have been replaced by glycine residues by mutation of the cloned genes for both the α and β subunits of hemoglobin.  With the tetrameric mutant hemoglobin (all subunits being mutant, α H F8 G, β H F8 G), it was found that the “proximal” coordination bonds to hemes in the mutant protein could be replaced by having the small molecule imidazole in the buffers.  Oxygen binding curves for the tetrameric mutant hemoglobin were measured.    A. The degree of cooperativity in oxygen binding for the mutant hemoglobin (with imidazole present) would be expected to   1)  increase 2)  decrease 3)  not be affected)   compared with the normal protein.   B. Justify your answer to part A in terms of what you know about the structural basis of cooperativity in hemoglobin.      C. How would the Hill coefficient for the mutant be expected to change compared with nH for normal hemoglobin, which is ~3?
The codon change (Gly-12 to Val-12) in human rasH that convertsit to oncogenic rasH has been associated with many types ofcancers. For this reason, researchers would like to develop drugs toinhibit oncogenic rasH. Based on your understanding of the Rasprotein, what types of drugs might you develop? In other words,what would be the structure of the drugs, and how would theyinhibit Ras protein? How would you test the efficacy of the drugs?What might be some side effects?

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Concepts of Genetics (12th Edition)

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Mitochondrial mutations; Author: Useful Genetics;https://www.youtube.com/watch?v=GvgXe-3RJeU;License: CC-BY