Gene, genetic defect

Alterations to the P53 gene are the most common genetic defects known in cancer [5]. The protein product of P53 is involved in a number of pathways that directly and indirectly lead to apoptosis. Many genes that are involved in apoptosis can be induced by this protein, which is a transcriptional transactivator. The emerging hypothesis is that p53 is a central node of a complex apoptotic network that may function differ ently in diver se cell types and tissues. For example, Bax, the prototype proapoptotic member of the Bcl2 family, can be transcriptionally induced by p53 in certain, but not all, cell types. Like p53, Bax can modulate the extent to which cells are sensitive to apoptosis caused by therapeutic agents. 

CYP21 catalyzes steroid C21 hydroxylation required for cortisol biosynthesis. Genetic defects in this gene cause congential adrenal hyperplasia. 

N2. Nakajima, H., Kono, N Yamasaki, T Hotta, K., Kawachi, M Kuwajima, M., Noguchi, T., Tanaka, T., and Tarui, S Genetic defect in muscle phosphofructokinase deficiency Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5 -splice site. J. Biol. Chem. 265, 9392-9395 (1990). 

Although human narcolepsy is not typically associated with orexin gene mutations, the orexin / model is most similar to the case of a narcoleptic-cataplectic child, severely symptomatic from infancy, who has a genetic defect in orexin production and release (Peyron et al., 2000). Thus, constitutive orexin deficiency alone in the presence of otherwise histologically normal orexin neurons... 

Albert Tauber. I d like to give a reference that everyone knows. Sickle-cell is commonly evoked as a great reductionist victory. I treat many patients with sickle-cell anemia, and I can tell you that the genetic defect is not the disease, because the disease manifestation is highly variable. Some patients have an enormous number of pain-crises. Some patients have a lot of haemolysis that s red-cell destruction. Other patients have pulmonary hypertension. And it s obvious that the disease that we call sickle-cell anemia is an extraordinarily complex phenomenon interacting with many many different systems and many other genes. And the bottom line, from a clinical perspective, which is the phenomenon that we call sickle-cell anemia, is that the sickle-cell gene is necessary but not sufficient for the disease. 

To date, the majority of gene therapy trials undertaken aim to cure not inherited genetic defects, but cancer. The average annual incidence of cancer reported in the USA alone stands at approximately 1.4 million cases. Survival rates attained by pursuit of conventional therapeutic strategies (surgery, chemo/radiotherapy) stand at about 50 per cent. 

Lactate dehydrogenase deficiency is an autosomal recessive myopathy caused by a genetic defect of the muscle subunit, which is encoded by a gene on chromosome 11 (type XI, Fig. 42-1). Thus far, several Japanese families and two Caucasian patients with this disease have been described. The clinical picture is characterized by cramps and myoglobinuria after intense exercise. 

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