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Unlocking Your Genetic History

Rutledge Hill Press

Contents

Acknowledgments........................................................................xiIntroduction: Who Should Read This Book?...............................................11. Ignorance Is Not Bliss: Know Your Family's Health History...........................52. Dominant and Recessive Diseases: Our Genetic Inheritance............................133. When Genes Go Bad...................................................................414. Compiling Your Family's Health History..............................................615. Do You Speak Medicalese?............................................................716. Draw Your Pedigree..................................................................977. What Have I Found?..................................................................1098. Common and Important Genetic Diseases...............................................1239. Tracking Your Genes: Molecular Genealogy............................................17110. Y Chromosome Testing: Your Father's Father's Father ...............................18711. Mitochondrial DNA: Tracking Mom's Line.............................................21512. More Information on the Internet...................................................23313. Ethics, Privacy, and the Future of Genetics and Genealogy..........................249Epilogue...............................................................................263Appendix A: Forms for Compiling Your Family's Health History...........................267Appendix B: National Genealogical Society Standards and Guidelines.....................275Glossary...............................................................................281Bibliography...........................................................................289Index..................................................................................295

Chapter One

Gilda Radner was ill. One of the original members of the television show Saturday Night Live, comic genius Radner did not realize that her body contained a ruthless ticking genetic time bomb-and it had just exploded. Somewhere deep in her pelvis, a single gene, a mistake, one that she had unknowingly inherited, was set in motion. A single isolated cell containing this mutated gene began unconstrained relentless growth, multiplying needlessly and destructively. A cancer was forming; a mass of cells unresponsive to the body's normal control had been created. Suffering from abdominal swelling, bloating, fatigue, and vague stomach pains that were initially thought by various doctors to be due to the flu or exhaustion, Radner was finally diagnosed with advanced ovarian cancer. Born in Detroit in 1946, she was then only 40 years old. Radner endured over two years of surgery, chemotherapy, and radiation therapy, only to die in 1989 at the age of 42. She could not know that her family history of ovarian cancer put her at a brutally high risk of developing the disease. Had the genetic and familial link of ovarian cancer been more widely known, had the significance of her family's medical pedigree been understood, and had the relevance of her ethnic heritage been recognized, she would have known that having an aunt, a grandmother, and a cousin who died from ovarian cancer and a mother who had breast cancer was extraordinarily significant to her own health.

Ovarian cancer is a silent cancer; growing slowly but relentlessly, it shows few symptoms until the disease is advanced. Early detection, however, can be curative. 5 While many ovarian cancers appear to arise spontaneously without a positive family history, some are hereditary. In general, a family history of ovarian cancer, especially if two or more close relatives are affected, is an important risk factor. We now know that at least two mutated genes, BRCA1 and BRCA2, predispose a woman to breast and ovarian cancer. These were discovered in 1994 to 1995, less than a decade after Radner's death. If a woman carries a diseased copy of BRCA1, she has a 65 percent chance of developing breast cancer by the age of 70 and a 39 percent chance of developing ovarian cancer. For BRCA2, the risks are 45 and 11 percent, respectively. About one in 50 Ashkenazi Jews, who trace their origin to central and eastern Europe, are known to carry abnormal BRCA1 or BRCA2 genes and are at increased risk for ovarian and breast cancer. Although Radner died before the BRCA gene mutations were discovered, given her family history, her early age when she was diagnosed, and her Jewish and Lithuanian heritage, she probably carried one of these genes.

Family Health History

Few of us know our family's health history or have taken the time to compile and analyze it. For instance, not until age 60 did U.S. Secretary of State Madeline Albright, who was raised a Roman Catholic, learn that she came from a family of Czechoslovakian Jews. For some of us, our grandparents were born elsewhere, such as in Europe or Asia. How much do we know about their brothers and sisters living outside of the United States? Are you in contact with all of your cousins? Do you know the state of their health? We live in a highly mobile society, with relatives often scattered around the country. Do you know how they are doing? In Gilda Radner's case, while she knew her family's health history, she could not understand its significance to her own health. Back in the early 1980s, far less was known about the relevance of genetics to family cancers. The past two decades have seen a virtual explosion in genetic knowledge, information that may be significant to you and your family.

As you compile your family's health history, you may be surprised that what seems to be an isolated disease actually affects several members of your family and therefore might put you and other members of your family at increased risk. For instance, if you find several family members with heart attacks, especially if they occur at a young age, you should realize that you might also be at risk. As genealogists have long known, it is important to research the whole family. Just as tracking the migration of a great-great-uncle might show you the location of your great-great-grandfather, so too might finding out the health history of a second cousin apply to your own health. Even if you are health conscious, eating a healthy diet and exercising regularly, you may still fall victim to your genes.

One Friday in 2002, Darryl Kile, one of the most respected pitchers for the St. Louis Cardinals, went to dinner with his brother the night before a baseball game against the Chicago Cubs in Wrigley Field. At approximately ten o'clock, he returned to the Cardinals' team hotel on Michigan Avenue. The following morning, two hours before the game was to start, the team realized that Kile was not present and called the hotel. Hotel workers had to force open the door, locked from the inside, to find the 33-year-old baseball pitcher dead in his bed. The 6 foot 5 inch athlete had appeared to be in perfect health. Kile had passed the team's spring training physical examination, including routine ECG and blood tests. The team doctor said he had no known health problems and was not on medication. Kile's autopsy revealed an 80 to 90 percent blockage of two of his coronary arteries by atherosclerotic plaques, so-called "hardening of the arteries." The coronary arteries are the arteries that supply the heart with blood and oxygen. It was assumed that the plaques in the coronary arteries blocked the blood supply to his heart and caused his death. His heart was approximately 25 percent larger than normal, indicating advanced and probably longstanding heart disease. During the previous spring training, the players, as part of their medical evaluation, had been given an extensive medical questionnaire that included questions about the family's medical history. Kile had made no mention of the fact that his father had died of heart disease in 1993 at the age of 44. Darryl Kile's death from a heart attack at 33 points out the importance of knowing your family's health history, knowing its importance to you, and sharing this information with your doctor. A family history of heart disease at an early age is one of the major risk factors for developing coronary artery disease. With early detection, coronary heart disease can be treated effectively.

Another athlete who also died prematurely and who also had a family history of early death from coronary artery disease was Jim Fixx. During the 1970s, jogging became an American pastime and, for some, an obsession. A completely new industry sprang up to provide supplies to runners and joggers. It was Fixx, the most famous jogger in America, who through his books almost single-handedly brought the sport of jogging to the American public. One day in 1984, while visiting Vermont, he went for a run and never returned. His body was found on the side of the road. At the age of 52, in peak physical condition, running 10 miles a day, Fixx had died on a run. An autopsy found three of his coronary arteries extensively damaged by atherosclerosis. His father had died of heart disease at age 43. With early diagnosis, effective treatment would have been possible.

Many less life-threatening, but nevertheless serious, diseases also have a genetic basis. If you are a woman and approaching menopause and you know that your mother and aunts had signs of significant osteoporosis, you might consider calcium supplements, exercise, and getting a base-line bone density study. A family history of psychiatric disorders could indicate that you are at higher risk for depression or bipolar disorder and that if you begin to show symptoms, you should seek medical attention. Having several close relatives who had heart attacks at an early age suggests that it is time to have your cholesterol checked. Heart disease, cancer, diabetes, Alzheimer disease, and any one of the thousands of specific genetic syndromes matter to you if they have occurred in your family. The more you know about your family's genetic history, the more you know about the health risks you, your children, and your grandchildren face. Knowing your family's health history can be invaluable in helping you modify your lifestyle to prevent illness or to arrange for periodic monitoring by screening tests. For instance, if you know that type 2 or adult-onset diabetes is present in your family, you should keep your weight down and be aware of the early warning signs of the illness.

It Runs in the Family

Writing this book made me more aware of how often family health history is part of our everyday news. As I was typing one Sunday, I heard that the actress Katharine Hepburn had died. Listening to her biography on one of the cable news networks that night, I perked up when I heard that depression and suicide run in her family. We now know that the affective disorders, depression and manic-depression, do indeed have a genetic component. I was even more interested when it was reported that Hepburn inherited some strange neurological disorder. Apparently, by the 1970s, it was widely rumored that Hepburn had Parkinson disease. At the time of her last major movie, On Golden Pond, her head was seen to shake visibly. She repeatedly denied that she had Parkinson disease, describing it as the "family shakes" that "runs in my family."

Neurological or nervous system genetic diseases are complex. Many of them, such as Huntington disease or chorea, Parkinson disease, and Friedreich ataxia, are named after their describer. Some are well known and their genetics are understood; many others are obscure. I could not help wondering if the "family shakes" that Hepburn described was ever diagnosed. Was it one of the known neurological diseases, or does her family have some unique, unknown malady that has never been described? It "runs in the family" is exactly the description one hears when there is an inherited genetic disease.

Genetics

A hundred years ago in America, the major killers were infectious diseases. Today, while they are still dangerous and even threatening to make a comeback, most infectious diseases can be treated. Many are controlled, especially the crippling childhood infections such as diphtheria, whooping cough, and tetanus that killed so many of our ancestors' children. With the control of infections, with better nutrition and living standards, with good public health and sanitation, the major killers in America have shifted from the 19th and early 20th century infectious diseases to cardiovascular disease, diabetes, and cancer. More and more, we are beginning to understand the role of genetics in these more chronic killers. One in 20 Americans has a disease with a major genetic component. If you consider that cancer, cardiovascular disease, diabetes, and others, while having an environmental component, also have a genetic predisposition, then probably far more than one in 20 Americans are affected by their genetic makeup.

The end of the 20th century and beginning of the 21st is a turning point, a medical revolution similar to the one that occurred at the end of the 19th and beginning of the 20th century. Until the 1880s, physicians believed that disease was caused by bad air, filth, or some other environmental factor. The last two decades of the 19th century saw an enormous change come over medicine. With the discovery that bacteria caused disease, medicine left the dark ages. The causes of such dreaded killers as typhoid, cholera, malaria, and tuberculosis were discovered. Knowledge that bacteria could cause postoperative infections revolutionized surgery, as antiseptic surgical techniques were adopted. Treatment, however, lagged behind. Early in the 20th century, physicians could only stand by helplessly as they watched their patient die from a staph infection, waste away from tuberculosis, or succumb to malaria. With the discovery of antibiotics in the middle of the 20th century, physicians could finally act on the knowledge they had accumulated and begin to cure patients of their infections. We are now beginning a second understanding, the importance of our genetic makeup to our health. But like the physicians of the early 20th century, while in some cases we understand quite well the genetics of a disorder, we can't intervene to repair the genetic defect. We can only stand by and watch as a 40-year-old man who has tested positive for the gene that causes Huntington disease waits for his inevitable physical and mental deterioration.

Human genetics was born at the beginning of the 20th century. Initially, its influence on medicine was minimal. William Osler's The Principles and Practice of Medicine had, by the turn of the century, become the most recognized and most frequently consulted textbook of medicine. A review of its 1,079 pages finds a 50-page section devoted to "Constitutional Disease," including some genetic diseases such as diabetes and hemophilia, as well as such nongenetic diseases as rheumatic fever (an infection) and scurvy (a vitamin deficiency). A review of the remainder of the book finds a few additional pages describing what we now know to be genetic diseases. In contrast, 72 pages are devoted to tuberculosis alone. Genetics continued to lag behind other medical advances during the early 20th century. But by the middle of the century, we discovered that the molecule DNA was the unit of heredity. Genetics began to advance rapidly, and 50 years later, the entire human DNA sequence, the human genome, has been decoded. As in the 19th century, the last two decades of the 20th century saw a profound shift in medical thinking. The field of genetics grew, many genetic diseases were defined, and many specific disease genes identified. Prenatal diagnosis and identification of individuals at risk are now possible for many important genetic diseases. The "final draft" of the human genome, our total and complete genetic material, was announced in 2003, on the 50th anniversary of the discovery of DNA by James Watson and Francis Crick. The decoding of the human genome, the DNA sequence of our 30,000 genes, promises to have as profound an effect on the practice of medicine as did the discovery that germs cause disease.

* * *

Clearly, there are many advantages to tracing your genetic history. But before you begin, you need to understand the concept of genes, developed long ago in a small monastery garden, and how some genes are recessive and others dominant, resulting in recessive and dominant diseases. These single-gene diseases have played a significant role in our history and remain important today.

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Excerpted from Unlocking Your Genetic Historyby Thomas H. Shawker Copyright © 2007 by Thomas H. Shawker. Excerpted by permission.
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