Positional cloning can be used to localize fragments of DNA representing genes prior to isolating the DNA. An example of the use of positional cloning is the cloning of the gene responsible for CF. By studying the patterns of inheritance of the disease and then comparing these with known chromosomal markers (linkage analysis), it was possible, without knowing the function of the gene, to locate the gene on human chromosome 7. Then, by using a technique known as chromosome walking, the gene was localized to a DNA sequence that encodes a protein now known as the cystic fibrosis transmembrane conductance regulator (CFTR). This protein, previously unknown, was shown to be defective in CF patients and could account for many of the symptoms of the disease. Like functional cloning, positional cloning has the advantage that specific knowledge of the protein is not required. It is also directly relevant to the understanding of human disease, and it can provide important new biological targets for drug development and the treatment of disease.
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