The human β-globin wild-type allele and a certain mutant allele are identical in sequence except for a single base-pair substitution that changes one nucleotide at the end of intron 2. The wild-type and mutant sequences of the affected portion of pre-mRNA are

Speculate about the way in which this base substitution causes mutation of β-globin protein.

The two DNA and polypeptide sequences shown are for alleles at a hypothetical locus that produce different polypeptides, both five amino acids long. In each case, the lower DNA strand is the template strand:

Based on DNA and polypeptide sequences alone, is there any way to determine which allele is dominant and which is recessive? Why or why not?

Many human genes are known to have homologs in the mouse genome. One approach to investigating human hereditary disease is to produce mutations of the mouse homologs of human genes by methods that can precisely target specific nucleotides for mutation.

Despite the homologies that exist between human and mouse genes, some attempts to study human hereditary disease processes by inducing mutations in mouse genes indicate there is little to be learned about human disease in this way. In general terms, describe how and why the study of mouse gene mutations might fail to produce useful information about human disease processes.

Many human genes are known to have homologs in the mouse genome. One approach to investigating human hereditary disease is to produce mutations of the mouse homologs of human genes by methods that can precisely target specific nucleotides for mutation.

Numerous studies of mutations of the mouse homologs of human genes have yielded valuable information about how gene mutations influence the human disease process. In general terms, describe how and why creating mutations of the mouse homologs can give information about human hereditary disease processes.

The human β-globin wild-type allele and a certain mutant allele are identical in sequence except for a single base-pair substitution that changes one nucleotide at the end of intron 2. The wild-type and mutant sequences of the affected portion of pre-mRNA are

This is one example of how DNA sequence change occurring somewhere other than in an exon can produce mutation. List other kinds of DNA sequence changes occurring outside exons that can produce mutation. In each case, characterize the kind of change you would expect to see in mutant mRNA or mutant protein.

Mutations in the CFTR gene result in cystic fibrosis in humans, a condition in which abnormal secretions are present in the lungs, pancreas, and sweat glands. The gene was mapped to a 500-kb region on chromosome 7 containing three candidate genes.

How would you prove that your chosen candidate is the CFTR gene?

Mutations in the CFTR gene result in cystic fibrosis in humans, a condition in which abnormal secretions are present in the lungs, pancreas, and sweat glands. The gene was mapped to a 500-kb region on chromosome 7 containing three candidate genes.

Using your knowledge of the disease symptoms, how would you distinguish between the candidate genes to decide which is most likely to encode the CFTR gene?

In a bacterial culture in which all cells are unable to synthesize leucine (leu⁻), a potent mutagen is added, and the cells are allowed to undergo one round of replication. At that point, samples are taken, a series of dilutions are made, and the cells are plated on either minimal medium or minimal medium containing leucine. The first culture condition (minimal medium) allows the growth of only leu⁺ cells, while the second culture condition (minimal medium with leucine added) allows growth of all cells. The results of the experiment are as follows:

What is the rate of mutation at the locus associated with leucine biosynthesis?