Genetics defect

The Human Genome Project is also vital to medicine. A number of human diseases have been traced to genetic defects, whose positions within the human genome have been identified. Among these are... 

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. 

A disease whose pattern of familial aggregation differs from that expected fi om the Mendelian inheritance of a single genetic defect. 

There are few definitive data to substantiate the efficacy of LTRA therapy in refractory asthma, except for patients with aspirin-sensitive asthma. This is a fairly uncommon form of asthma that occurs generally in adults who often have no prior (i.e., childhood) history of asthma or atopy, may have nasal polyposis, and who often are dependent upon oral corticosteroids for control of their asthma. This syndrome is not specific to aspirin but is provoked by any inhibitors of the cycloxygenase-1 (COX-1) pathway. These patients have been shown to have a genetic defect that causes... 

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

Etiology Trauma, viral infections, ischemia, inflammation, genetic defects Neuropathy, genetic defects Peripheral inflammation, peripheral neuropathy, trauma, genetic defects, spinal cord injury, inflammation in the central nervous system ... 

LGD linked to chromosome 15 is of recessive inheritance, with the onset of disease at around the age of eight years and confinement to a wheelchair around the age of 30 years. The underlying genetic defect in this group is still unclear. 

Dutartre H, Bussetta C, Boretto J, Canard B (2006) General catalytic deficiency of hepatitis C virus RNA polymerase with an S282T mutation and mutually exclusive resistance towards 2 -modified nucleotide analogues. Antimicrob Agents Chemother 50 4161 169 Elferink RO, Groen AK (2002) Genetic defects in hepatobiliary transport. Biochim Biophys Acta... 

Demonstration ofthe nature ofthe genetic defects in cystic fibrosis. 

The genetic defects known as thalassemias result from the partial or total absence of one or more a or P chains of hemoglobin. Over 750 different mutations have been identified, but only three are common. Either the a chain (alpha thalassemias) or P chain (beta thalassemias) can be affected. A superscript indicates whether a subunit is completely absent (a or p ) or whether its synthesis is reduced (a or P ). Apart from marrow transplantation, treatment is symptomatic. 

In some Asian populations and Native Americans, alcohol consumption results in increased adverse reactions to acetaldehyde owing to a genetic defect of mitochondrial aldehyde dehydrogenase. 

Various genetic defects in PRPP synthetase (reaction 1, Figure 34-2) present clinically as gout. Each defect— eg, an elevated increased affinity for ribose 5-... 

Hypouricemia and increased excretion of hypoxanthine and xanthine are associated with xanthine oxidase deficiency due to a genetic defect or to severe liver damage. Patients with a severe enzyme deficiency may exhibit xanthinuria and xanthine lithiasis. 

Modified from Olkonnen VM, Ikonen E Genetic defects of intra-cellular-membrane transport. N Eng J Med 2000343 1095. Certain related conditions not listed here are also described in this publication. l-cell disease is described in Chapter 47. The majority of the disorders listed above affect lysosomal function readers should consult a textbook of medicine for information on the clinical manifestations of these conditions. 

Olkkonen VM, Ikonen E Genetic defects of intracellular-membrane transport. N Engl J Med 2000 343 1095. 

C. J. "Intrauterine Diagnosis of Genetic Defects Results, Problems, and Follow-up of 100 Cases In a Prenatal Genetic Detection Center". Am. J. Obstet. Gynecol., (1974), 118> 897-905. 

For nearly 80% of patients with epilepsy, the underlying etiology is unknown.8 The most common recognized causes of epilepsy are head trauma and stroke. Developmental and genetic defects are the cause of about 5% of cases of epilepsy. Central nervous system (CNS) tumors, central nervous system infections, and neurodegen-erative diseases are other common causes. Other important causes of epilepsy are human immunodeficiency virus infection or neuro-cysticercosis infection, primarily occurring in Latin America. 

Murine models have been instrumental in representing human disease in vivo. Transgenic approaches have produced mice with genetic defects that promote susceptibility to fibrosis, including abnormal expression of chemokines and/or chemokine receptors. These models have elucidated the factors that are conducive to fibrosis and have thus revealed the central roles of certain chemokines and chemokine receptors. Conventional methods of inducing... 

K18. Kelley, W. N Rosenbloom, F. M., Henderson, J. F and Seegmiller, J. E., Adenine phosphori-bosyltransferase deficiency Apreviously undescribed genetic defect in man. J. Clin. Invest. 47, 2281-2289 (1968). 

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