Abstract: Genes causing disease may be found either by the process known as 'positional cloning', or by examining candidate genes. Positional cloning relies on the demonstration of genetic linkage (co-inheritance) 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 positional cloning approach has the advantage of not requiring any pre-existing knowledge of the pathophysiology of the disease. Genetic linkage in complex disorders, however assessed, often replicates poorly, at least in the early stages. This is because linkage to a heterogeneous trait will normally only be found fortuitously, in samples that contain an exceptional proportion of individuals or families influenced by that particular gene. The genetic basis for asthma is gradually becoming more certain; the methodological tools for finding genetic linkage and association are now established, and it is likely that all the important genes and their variants will be found in future.
Publication Year: 1998
Publication Date: 1998-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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