A significant number of mutations in the HBB gene that cause human β-thalassemia occur within introns or in upstream noncoding sequences. Explain why mutations in these regions often lead to severe disease, although they may not directly alter the coding regions of the gene.

Several types of mutation are identified and described. These include (1) promoter mutation, (2) splice site mutation, (3) missense mutation, (4) frameshift mutation, and 5) nonsense mutation. Match the following mutation descriptions with the type(s) of mutations listed above. More than one mutation type might match a description.

A mutation that changes several amino acids in a protein and results in a protein that is shorter than the wild-type product.

A glycine residue is in position 210 of the tryptophan synthetase enzyme of wild-type E. coli. If the codon specifying glycine is GGA, how many single-base substitutions will result in an amino acid substitution at position 210? What are they? How many will result if the wild-type codon is GGU?

Refer to the genetic coding dictionary to respond to the following:

A base-substitution mutation that altered the sequence shown in part (a) eliminated the synthesis of all but one polypeptide. The altered sequence is shown here:

5'-AUGCAUACCUAUGUGACCCUUGGA-3'

Determine why.

Dominant mutations can be categorized according to whether they increase or decrease the overall activity of a gene or gene product. Although a loss-of-function mutation (a mutation that inactivates the gene product) is usually recessive, for some genes, one dose of the normal gene product, encoded by the normal allele, is not sufficient to produce a normal phenotype. In this case, a loss-of-function mutation in the gene will be dominant, and the gene is said to be haploinsufficient. A second category of dominant mutation is the gain-of-function mutation, which results in a new activity or increased activity or expression of a gene or gene product. The gene therapy technique currently being used in clinical trials involves the 'addition' to somatic cells of a normal copy of a gene. In other words, a normal copy of the gene is inserted into the genome of the mutant somatic cell, but the mutated copy of the gene is not removed or replaced. Will this strategy work for either of the two aforementioned types of dominant mutations?

Using the adenine–thymine base pair in this DNA sequence

...GCTC...

...CGAG...

Give the sequence after a transversion mutation.

Using the adenine–thymine base pair in this DNA sequence

...GCTC...

...CGAG...

Give the sequence after a transition mutation.

The partial amino acid sequence of a wild-type protein is

… Arg-Met-Tyr-Thr-Leu-Cys-Ser …

The same portion of the protein from a mutant has the sequence

… Arg-Met-Leu-Tyr-Ala-Leu-Phe …

Give the sequence of the wild-type DNA template strand. Use A/G if the nucleotide could be either purine, T/C if it could be either pyrimidine, N if any nucleotide could occur at a site, or the alternative nucleotides if a purine and a pyrimidine are possible.

The partial amino acid sequence of a wild-type protein is

… Arg-Met-Tyr-Thr-Leu-Cys-Ser …

The same portion of the protein from a mutant has the sequence

… Arg-Met-Leu-Tyr-Ala-Leu-Phe …

Identify the type of mutation.