There are at least eight known progressive neuronal dysfunction diseases in humans that are caused by abnormal numbers of CAG repeats within the coding regions of specific genes. Genes carrying such mutations are typically of the gain-offunction class and often share a common mechanism of progressive pathogenesis. Why are such genes "gain-of-function"? Speculate on why such diseases are probably caused by a common mechanism of pathogenesis.

Answer: Genes with abnormal numbers of CAG repeats are classified as "gain-of-function" because the mutations result in altered or enhanced activity of the gene product. The elongated polyQ tracts lead to a toxic gain of function, causing the protein to misfold and aggregate, which in turn has detrimental effects on the cell, causing cellular dysfunction and neuronal cell death. The common mechanism of pathogenesis in progressive neuronal dysfunction diseases caused by abnormal CAG repeats is likely related to the toxic gain of function due to elongated polyQ tracts. Since these diseases often have similar symptoms, and involve mutations in different genes with CAG repeats, the toxic effects of abnormally elongated polyQ tracts appear to be a common pathogenic process. This includes intracellular protein aggregation, cellular dysfunction, disruption of protein-protein interactions, and ultimately, neurodegeneration.