The following chapters are considered together so that questions can easily follow the flow of genetic information from DNA to RNA to protein. The reader will need to consult the genetic code in figure 7 to answer some questions. CHAPTER 9 CHAPTER 10 CHAPTER 11 CHAPTER 12 Double Muscles DNA Structure and Replication Gene Action: From DNA to Protein Gene Expression and Epigenetics Gene Mutation Figure 6 Mutant myostatin causes “double muscles” and great strength. Caden and Jaden have a point mutation in intron 1 of the myostatin gene that lengthens exon 1 and shifts the reading frame in a way that generates a nonsense mutation that shortens exon 2. These changes are sufficient to impair functioning of myostatin protein in controlling stem cell activity in muscles. As a result, muscles overgrow. Caden and Jaden are only 13 years old, but their muscles are so powerful, thanks to their myostatin mutations, that they look like older bodybuilders. They both lift weights and run cross-country at school. As part of the research project they are participating in, their myostatin genes are sequenced, and gene expression is assessed in their muscle tissue and blood. The myostatin gene is on chromosome 2. When myostatin protein is made, it keeps muscles from growing too large. When the gene is absent or not sufficiently expressed, the control over muscle growth is lifted and muscles overgrow. Stem cells in the muscle “reawaken” and produce more cells. Myostatin protein is made in skeletal muscle tissue and secreted into the plasma, which is the liquid portion of blood. The myostatin gene has three exons and two introns. The precursor form of the protein is 335 amino acids long. The final form is a glycoprotein. Caden and Jaden have a G to A point mutation near the end of the first exon near the first intron (figure 6). This mutation alters splicing of the introns out of the mRNA in a way that lengthens the mRNA transcribed from exon 1 and produces a nonsense mutation in exon 2. The result: the gene doesn’t work, the muscles do not produce myostatin, and they overgrow.
Barbara, 62 years old, feels so strong and healthy that sometimes she forgets that she had cancer. She was only 36 years old when she found a lump in her left breast. Mammography, then a new technique, revealed the tumor, and it was successfully removed. At the time there were no genetic tests for breast cancer. A few months ago, when her son Dan was diagnosed with prostate cancer, his physician asked about a family history of cancer. Dan mentioned that his mother had had breast cancer at an early age. The doctor then urged Dan to ask his mother to be tested for the most common BRCA1 mutation, and if she had it, then he might want to be tested too. Mutations in BRCA1 can increase the risk of developing breast, ovarian, prostate, and possibly other cancers. After genetic counseling, Barbara took the test. She indeed had the most common mutation, and so Dan was tested and he had it, too. They chose to be tested so that they could alert younger family members, and Dan’s siblings, that they might have higher risk of developing these cancers. The family mutation was a deletion of an A and a G at the 185th nucleotide of the BRCA1 gene