Molecular Biology of the Lung: Volume II: Asthma and Cancer by Joanne T. Douglas, David T. Curiel (auth.), Prof. Robert A.

By Joanne T. Douglas, David T. Curiel (auth.), Prof. Robert A. Stockley (eds.)

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Transcription factors may be activated by many extracellular influences acting via surface receptors which lead to phosphorylation by several types of kinase [1, 2], or may be directly activated by ligands (such as corticosteroids, thyroid hormone and vitamins). Transcription factors may therefore convert transient environmental signals at the cell surface into long-term changes in gene transcription, thus acting as "nuclear messengers" [3]. Transcription factors may be activated within the nucleus, often with the transcription factor bound to DNA, or within the cytoplasm, resulting in exposure of nuclear localization signals and targeting to the nucleus.

If they are very close they will remain together through many generations. This process, the co-inheritance of stretches of adjacent genes, is known as genetic linkage. Positional cloning relies on the demonstration of genetic linkage of disease and genetic markers of known chromosomal localization. Once linkage is established, the linked region can be dissected by further genetic mapping with a dense array of closely linked markers. Genetic mapping is followed by physical mapping, the assembly of overlapping DNA clones covering the linked regions, and the eventual identification and sequencing of genes from the DNA.

The presence of an HLA association suggests that immune recognition of an unknown antigen may be part of the aetiology of ASA. The relative role ofHLA-DP in antigen presentation, compared with HLA-DR and HLA-DQ, is unknown. The results from the various studies therefore show that HLA-DR alleles do modify the ability to mount an IgE response to particular antigens. 0 or less. Thus class II HLA restriction seems insufficient to account for individual differences in reactivity to common allergens.

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