Chapter 7, Problem 21P

The physicist Stephen Hawking, famous for his theories about black holes, has lived past the age of 70 with amyotrophic lateral sclerosis (ALS), a paralyzing neurodegenerative disease that is usually fatal at a much younger age. Recently, geneticists discovered that a major cause of ALS is the unusual expansion of a hexanucleotide repeat (5′-GGGGCC-3′) that lies within a gene called C9ORF72, at a location outside of the gene’s open reading frame (ORF). A single expanded allele is sufficient to cause ALS, but the reason the disease allele is dominant remains unclear. Some experimental results support the theory that the allele makes a toxic RNA containing the expanded repeat. If this theory is correct, in what ways is the mutant ALS-causing allele similar to the mutant allele that causes Huntington disease? In what ways is it similar to the mutant allele that causes fragile X syndrome?