28. Robert Bost and Richard Cribbs studied a strain of E. coli (araB14) that possessed a nonsense mutation in the structural gene that encodes L-ribulokinase, an enzyme that allows the bacteria to metabolize the sugar arabinose (R. Bost and R. Cribbs. 1969. Genetics 62:1–8). From the araB14 strain, they isolated some bacteria that possessed mutations that caused the bacteria to revert back to wild type. Genetic analysis of these revertants showed that they possessed two different suppressor mutations. One suppressor mutation (R1) was linked to the original mutation in the L-ribulokinase and probably occurred at the same locus. By itself, this mutation allowed the production of L-ribulokinase, but the enzyme was not as effective in metabolizing arabinose as the enzyme encoded by the wild-type allele. The second suppressor mutation (Su^B) was not linked to the original mutation. In conjunction with the R1 mutation, Su^B allowed the production of L-ribulokinase, but Su^B by itself was not able to suppress the original mutation.

29.Achondroplasia is an autosomal dominant disorder characterized by disproportionate short stature—the legs and arms are short compared with the head and trunk. The disorder is due to a base substitution in the gene, located on the short arm of chromosome 4, for fibroblast-growth-factor receptor 3 (FGFR3).

Although achondroplasia is clearly inherited as an autosomal dominant trait, more than 80% of the people who have achondroplasia are born to parents with normal stature. This high percentage indicates that most cases are caused by newly arising mutations; these cases (not inherited from an affected parent) are referred to as sporadic. Studies have demonstrated that sporadic cases of achondroplasia are almost always caused by mutations inherited from the father (paternal mutations). In addition, the occurrence of achondroplasia is higher among the children of older fathers; approximately 50% of children with achondroplasia are born to fathers older than 35 years of age. There is no association with maternal age. The mutation rate for achondroplasia (about 4 × 10⁻⁵ mutations per gamete) is high compared with those for other genetic disorders. Explain why most spontaneous mutations for achondroplasia are paternal in origin and why the occurrence of achondroplasia is higher among older fathers.

30.Ochre and amber are two types of nonsense mutations. Before the genetic code was worked out, Sydney Brenner, Anthony O. Stretton, and Samuel Kaplan applied different types of mutagens to bacteriophages in an attempt to determine the bases present in the codons responsible for amber and ochre mutations. They knew that the ochre and amber mutations were suppressed by different types of mutations, which demonstrated that each is a different stop codon. They obtained the following results:

31.To determine whether radiation associated with the atomic bombings of Hiroshima and Nagasaki produced recessive germ-line mutations, scientists examined the sex ratio of the children of the survivors of the blasts. Can you explain why an increase in germ-line mutations might be expected to alter the sex ratio?