Case Study- Chapters 9–12

Case Study- Chapters 9–12     **** DUE 08/08/15******

From your course textbook Case Workbook to Accompany Human Genetics: Concepts and Applications, read the assigned case study in the following chapters:

    Chapters 9–12

In a 4- to 5-page Microsoft Word document, create a work sheet by answering the Questions for Research and Discussion provided for each case study. (Do not answer the multiple-choice questions).

Cite any sources in APA format.

                                   ******   Case study and questions   *****

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.

    11. Explain why all known myostatin mutations that cause double muscling are nonsynonymous (change the encoded amino acid sequence) rather than synonymous (do not change the amino acid sequence).

    12. Do you think that someone who is extra strong due to a myostatin mutation should be considered to have an unfair advantage in athletic competition?

    13. Suggest a medical treatment that would involve the use of myostatin.

4849Barbara, 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. This is a mutation most often seen in the Ashkenazi Jewish population. Barbara was adopted shortly after birth, so she hadn’t known she was in this population group. The BRCA1 gene is large—110 kilobases, including 22 exons. Three-quarters of the 100 known mutations in the gene shorten the protein product. One company owns the patent for the BRCA1 gene sequence, and it provides all genetic tests for cancers caused by mutations in this gene. The American Civil Liberties Union and several genetics organizations are challenging the fairness of the patent because it forces patients to use this company’s test, which is very costly.

Sometimes BRCA1 tests detect a mutation that hasn’t been seen or studied before. Such a result is reported to the patient as a “variant of unknown significance.” It can be very stressful to receive such incomplete clinical information.

Dan discusses his cancer, and the BRCA1 gene, with his children. Only Robin has reached 18, the age at which genetic counselors advise genetic testing, but all Dan’s children are interested. Robin and Suzanne are more upset than their brothers, after learning that Ashkenazim with the mutation have an 86 percent chance of developing breast cancer. Some women who have the mutation actually have their breasts, and sometimes their ovaries, removed to prevent the cancer from developing. The sisters also read about tests based on gene expression profiling that can tell a woman whether her initial cancer is likely to recur and spread, and which drugs are likely to be effective.

    20. Look up U.S. Patent 5654155 at, which covers use of the BRCA1 gene’s DNA sequence. Discuss what the patent covers and whether you think companies should be permitted to patent gene sequences.

    21. Do Web research or consult Chapter 18 in the textbook to name a gene, other than BRCA1, that increases risk of developing breast cancer when mutant. What is the process or mechanism that the mutation disrupts?

    22. Discuss how alternate splicing can complicate the study of mutations in the BRCA1 gene.

    23. Distinguish between a hereditary germline cancer, such as those caused by BRCA1 mutations, and cancers that result from two somatic mutations in the same gene in the same cell.

    24. Explain how mutations in the same gene can cause different types of cancer.

The Mediterranean Diet

Tawanda has tried many diets, especially since her mother had gastric bypass surgery, but none has led to significant, lasting weight loss. Nonetheless she is hopeful about the Mediterranean diet.

The eating plan traces its roots to nutritionist Ansel Keys, who visited Crete, the largest Greek island, with the military in the 1940s. He noted that the isolated, mountainous villages there had many very old and healthy residents and very little cancer and cardiovascular disease. This was in sharp contrast to the overfed, overstressed businessmen in the United States whom Keys studied after the war.

5152Keys then led a 15-year investigation, called the Seven Country Study, to assess diet and cardiovascular disease among the people in Crete, Finland, Japan, Italy, the Netherlands, Yugoslavia, and the United States. The longest-lived people, with the healthiest hearts and blood vessels, were consistently those living on Crete. Although they had very similar cholesterol profiles to the people in other populations, their diet emphasized olive oil, which contains mostly monounsaturated fats, rather than the saturated fats found in meat and dairy products. Keys’ hypothesis emerged: does a diet rich in saturated fats set the stage for atherosclerosis, the deposition of plaque on blood vessel inner linings?

The Seven Country Study found that Japan was the next-healthiest group, with the other five countries trailing far behind. Finland’s government tested the atherosclerosis hypothesis with the Karelia Study. Once study participants sharply reduced the amount of saturated fat they ate, the incidence of cardiovascular disease plummeted.

Today’s Mediterranean diet emphasizes fruits, vegetables, cereals, fish, and legumes. The carbohydrates are complex and not processed, with high fiber content from the whole grains. Nuts, seeds, and fish are eaten often, but the people consume very little dairy, red meat, and eggs which limits intake of saturated fats. The plan helps in controlling weight and promoting heart health—perfect for Tawanda, because both her parents take drugs to lower their serum cholesterol level and blood pressure. These risk factors, plus Tawanda’s weight challenges, she knows, greatly elevate her risk of developing cardiovascular disease. When Tawanda tells Suzanne about her plans to start the diet, her cousin is skeptical. She’s read about it, too.      

           “Sounds great! But how do you know that what works in Crete would work for you? The lifestyle there isn’t exactly like it is here, nor is the environment.”

“What do you mean?”

“Crete’s a mountainous, rocky island, where the people grow most of their own food,” says Suzanne. “So their fruits and vegetables are fresh and grown without pesticides, and they probably get a lot of exercise growing everything and climbing everywhere. They have no cities, so there’s no pollution. Probably not much stress. Even the seasons are different, with short, mild winters yet long summers. Their cheese is homemade, their olive oil pressed from their own olives. It seems like some other factors might contribute to their good health, don’t you think?” asks Suzanne.

“I guess so. It also explains some of the stranger things on the diet—like fish heads, snails, and octopus. I can do without those. But Googling Mediterranean diet is frustrating. All you get are ads to buy olive oil. I wonder what it is in the oil that’s so good for you, and how it promotes health?”

Researchers in Barcelona, Spain, also wondered what makes olive oil healthful. They conducted a study on six male and four female volunteers, all young and healthy, to assess the effects of increased olive oil consumption on gene expression in the human body. Their hypothesis was that changes in gene expression—genes that are transcribed at significantly higher or lower rates when a person eats a lot of olive oil for a month—are 5253more sensitive than measuring standard biomarkers, such as cholesterol (high-density lipoproteins or HDLs, and low-density lipoproteins or LDLs), glucose, or triglyceride levels.

        The researchers already knew what was in olive oil. In addition to monounsaturated fats, the oil contains vitamins A, E, and K as well as organic compounds called phenols that fight oxidative damage and lower plasma lipid levels and inflammation. Studies that gave high doses of the oil or its components to rodents showed lowered inflammation and blood pressure. These results inspired the current pilot study on the ten volunteers.

The participants underwent a one-week initial “washout” period when they ate only sunflower oil and limited their intake of anti-oxidants, such as fruits and vegetables. This would ensure that the study did not pick up effects from past diet. Then for four weeks they ate a great deal of virgin olive oil. Gene expression profiles were done on the types of white blood cells (lymphocytes and monocytes) known to die in atherosclerosis. These dead cells contribute to the buildup of plaque on the interior walls of blood vessels.

The study used DNA microarrays spotted with probes to the entire human genome. Compared to the microarrays done before the switch to the olive oil diet, the microarrays done after showed increased expression of 1034 genes and decreased expression of 628 genes in the tested white blood cells. As expected, the standard biomarker tests for cholesterol, oxidative stress, inflammation, and glucose levels remained unchanged. The gene expression route was clearly more sensitive. But what did the results mean?

Overall, the pattern of gene expression in response to the olive oil diet revealed an activation of protein synthesis in general, but specifically of genes involved in metabolizing lipids, fatty acids, and steroids. These results suggest that the white blood cells were gearing up to handle something new in the diet. Some of the highly expressed genes encode chaperone proteins that assist in protein folding; ribosomal proteins; transcription factors; and proteins that assist in splicing mRNAs. Furthermore, several genes whose expression increased markedly during the olive oil diet are parts of pathways that affect the cardiovascular system and could therefore be protective (Table 5).


Table 5 Genes Whose Expression Increases on a High Olive Oil Diet




DNA repair















Anti-cell adhesion






      This preliminary study revealed that olive oil components begin to change metabolism in ways that benefit the cardiovascular system even before cholesterol and other standard biomarkers noticeably change. Ongoing studies are looking at more people to investigate individual variation in response to eating olive oil. In the meantime, Tawanda is eating more like a resident of Crete and exercising. If she can stick to this plan, she may never need medication to lower her cholesterol or blood pressure—or gastric bypass surgery.

34. List the limitations in experimental design for the Barcelona experiment.

    35. Outline a further study that can delineate how much olive oil is the most helpful for an individual in a particular population.

    36. Discuss factors that might contribute to whether a particular diet is effective in a particular individual.

    37. Design a test based on gene expression profiling that a person could use to predict which diet would work best.

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