Page 44 - Hematology_ Basic Principles and Practice ( PDFDrive )

16 Part I Molecular and Cellular Basis of Hematology

known to be abnormal, such as the globin genes in the thalassemia The most important impact of the genetic approach to the analysis
or sickle cell syndromes, the normal and pathologic anatomy of genes of biologic phenomena is the most indirect. Diligent and repeated
critical to major hematologic diseases can be established. In this application of the methods outlined in this chapter to the study of
manner, it has been possible to identify many mutations responsible many genes from diverse groups of organisms is beginning to reveal
for various forms of thalassemia, hemophilia, thrombasthenia, red the basic strategies used by nature for the regulation of cell and tissue
blood cell enzymopathies, porphyrias, and so forth. Similarly, single behavior. As our knowledge of these rules of regulation grows, our
base changes have been shown to be the difference between many ability to understand, detect, and correct pathologic phenomena will
normally functioning proto-oncogenes and their cancer-promoting increase substantially.
oncogene derivatives.
Third, cloned genes can be manipulated for studies of gene expres-
sion. Many vectors allowing efficient transfer of genes into eukaryotic SUGGESTED READINGS
cells have been perfected. Gene transfer technologies allow the gene
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of that gene or the behavior of its products to be analyzed. These in the same factory. Curr Opin Cell Biol 14:336, 2002.
surrogate or reverse genetics systems allow analysis of the normal Dykxhoorn DM, Novina CD, Sharp PA: Killing the messenger: Short RNAs
physiology of expression of a particular gene, as well as the patho- that silence gene expression. Nat Rev Mol Cell Biol 4:457, 2003.
physiology of abnormal gene expression resulting from mutations. Fischle W, Wang Y, Allis CD: Histone and chromatin cross-talk. Curr Opin
Fourth, cloned genes enhance study of their protein products. By Cell Biol 15:172, 2003.
expressing fragments of the gene in microorganisms or eukaryotic Grewal SI, Moazed D: Heterochromatin and epigenetic control of gene
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deduced from the DNA sequence can be prepared as the immu- animal development and disease. Dev Cell 11:441, 2006.
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Finally, all of the aforementioned techniques can be extended by Rev Cell and Mol Med 1–59, 2014.
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inconceivable ways the complexities of gene regulation. These activist Waddington S, Privolizzi R, Karda R, et al: A broad overview and review of
approaches to modifying gene structure or expression create the Crispr-CAS technology and stem cells. Curr Stem Cell Rep 2:9–20, 2016.
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