Many genetic diseases are caused by mutations in a single protein; studies on people with these diseases have shed light on the normal function of those proteins. As an example, consider Duchenne muscular dystrophy (DMD), the most common among the hereditary muscle-wasting diseases, collectively called muscular dystrophies. DMD, an X chromosome–linked disorder that affects 1 in 3300 boys, results in cardiac or respiratory failure and death, usually in the late teens or early twenties. The first clue to understanding the molecular basis of this disease came from the discovery that people with DMD carry mutations in the gene encoding a protein named dystrophin. As detailed in Chapter 17, this very large protein was later found to be a cytosolic adapter protein that binds to actin filaments that are part of the cytoskeleton (see Figure 1-13) and to a complex of muscle plasma-membrane proteins termed the sarcoglycan complex (Figure 1-31). The resulting large multiprotein assemblage, the dystrophin glycoprotein complex (DGC), links the extracellular matrix protein laminin to the cytoskeleton within muscle cells. Mutations in dystrophin, other DGC components, or laminin can disrupt the DGC-mediated link between the exterior and interior of muscle cells and cause muscle weakness and eventual death. The first step in identifying the entire dystrophin glycoprotein complex involved cloning the dystrophin-encoding gene using DNA from normal individuals and from patients with Duchenne muscular dystrophy.

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