1. The following amino acid sequence represents part of a protein. The normal sequence and four mutant forms are shown. By consulting Table 3-1, determine the double-stranded sequence of the corresponding section of the normal gene. Which strand is the strand that RNA polymerase “reads”? What would the sequence of the resulting mRNA be? What kind of mutation is each mutant protein most likely to represent?

Normal -lys-arg-his-his-tyr-leu-

Mutant 1 -lys-arg-his-his-cys-leu-

Mutant 2 -lys-arg-ile-ile-ile-

Mutant 3 -lys-glu-thr-ser-leu-ser-

Mutant 4 -asn-tyr-leu-

2. The following items are related to each other in a hierarchical fashion: chromosome, base pair, nucleosome, kilobase pair, intron, gene, exon, chromatin, codon, nucleotide, promoter. What are these relationships?

3. Describe how mutation in each of the following might be expected to alter or interfere with normal gene function and thus cause human disease: promoter, initiator codon, splice sites at intron-exon junctions, one base pair deletion in the coding sequence, stop codon.

4. Most of the human genome consists of sequences that are not transcribed and do not directly encode gene products. For each of the following, consider ways in which these genome elements might contribute to human disease: introns, Alu or LINE repetitive sequences, locus control regions, pseudogenes.

5. Contrast the mechanisms and consequences of RNA splicing and somatic rearrangement.

6. Consider different ways in which mutations or variation in the following might lead to human disease: epigenetic modifications, DNA methylation, miRNA genes, lncRNA genes.

7. Contrast the mechanisms and consequences of genomic imprinting and X chromosome inactivation.