Your Genetic Destiny

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Much in the news, inherited disease and genetic testing are complex and confusing issues that leave most asking: "So, what can I do with this promising information?" A powerfully helpful and authoritative guide, Your Genetic Destiny has the answers. From what tests to have taken, what the results mean, and when further genetic counseling is in order; from what foods to avoid to which medications to take and what other medical options are available, world-renowned geneticist Aubrey Milunsky demonstrates how ...

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Overview

Much in the news, inherited disease and genetic testing are complex and confusing issues that leave most asking: "So, what can I do with this promising information?" A powerfully helpful and authoritative guide, Your Genetic Destiny has the answers. From what tests to have taken, what the results mean, and when further genetic counseling is in order; from what foods to avoid to which medications to take and what other medical options are available, world-renowned geneticist Aubrey Milunsky demonstrates how knowledge of our genetic makeup can save our lives. Covering heart disease, hypertension, cancer, diabetes, mental illness, Alzheimer's disease, obesity, longevity, and infertility, Your Genetic Destiny is the most comprehensive, compassionate, and informed guide available for all concerned about the risks of inherited disease.

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Editorial Reviews

Nathaniel H. Robin
An excellent book with a great deal of factual genetic information... Nonmedical readers will find it very readable and understandable.
Journal of the American Medical Association
Library Journal
The recent mapping of the basic draft of the human genome means that scientists can now identify and sequence most of the 30,000 to 40,000 genes estimated to comprise the human genome. Next, researchers will need to discover how these genes work in order to understand how to prevent or cure disease. Therefore, the dramatic title of this book, authored by a board-certified clinical geneticist, is fairly premature and probably refers to medical genetics in another decade or two. While the book discusses genetic testing and counseling and covers the major diseases with genetic elements (heart disease, Alzheimer's, cancer, diabetes, etc.), there are several problems with the text. The technical language will certainly challenge the average reader, and a glossary is not included. The forthright, even blunt, tone in the sections discussing options for detecting and preventing birth defects may seem insensitive to some readers ("Not bothering to determine all of the risks and options prior to conceiving a child who may be doomed to a lifetime of pain and suffering could be construed as a form of child abuse"), while others may strongly object to the author's prescriptive advice. Steer consumers instead to James Wynbrandt and Mark Ludman's The Encyclopedia of Genetic Disorders and Birth Defects (Facts On File, 1999. 2d ed.), which is "the" authoritative text on the subject yet is understandable and easy-to-use. Not recommended Gail Hendler, Memorial Sloan-Kettering Cancer Ctr., New York Copyright 2001 Cahners Business Information.
Booknews
This is a paperbound edition of a 2001 book about which Book News wrote: A guide for general readers to genetic disorders, inherited diseases, and diseases caused by ethnic genes and too many or too few chromosomes. Milunsky (human genetics, pediatrics, obstetrics and gynecology, and pathology, Boston U.) explains also what genetic counseling is and who should seek it. Annotation c. Book News, Inc., Portland, OR (booknews.com)
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Product Details

  • ISBN-13: 9780738206844
  • Publisher: Da Capo Press
  • Publication date: 5/1/2002
  • Edition description: New Edition
  • Pages: 432
  • Product dimensions: 0.96 (w) x 6.00 (h) x 9.00 (d)

Meet the Author

Aubrey Milunsky, M.D., D.Sc., is Professor of Human Genetics, Pediatrics, Obstetrics and Gynecology, and Pathology at the Boston University School of Medicine. He is the author or editor of thirteen books and more than two hundred scientific papers.

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Read an Excerpt


Chapter One


What You Should Know, and Why


Contrary to popular belief, your genetic destiny is not preordained. True, you are born with a genetic blueprint that dictates the structure and functioning of your body. Notwithstanding this irrevocable fact of nature, you are not a hapless victim, inevitably bound to suffer the inexorable consequences of any flawed genes you may have inherited. Although every aspect of health and all disease is controlled, regulated, modulated, or influenced by your genes, genes are not the last word; there is much more you should know and much you can do to influence the outcome. The purpose of this book is to empower and encourage you to know your genes so that you can secure your own health and that of your loved ones.

    The first step is to develop and maintain as thorough a knowledge of your family medical history as possible (see Chapter 2). Second, remain attentive to the remarkable and rapidly escalating advances in genetics reflected daily in the mass media and on the Internet. Third, select a physician who understands the importance of genes and is willing to assist you in genetic health maintenance. Until recently, our genetic fate was like a big black box—sealed and impenetrable, unfathomable and irrevocable. This is no longer the case. You might well be surprised at how much new information has come to light on human genetics, and how relevant it is to you and your family. There is much in this book that you need to know, that could save your life and secure your health and those of all your loved ones. You do need to care, to know.


ToKnow Is to Care


Ignorance is not bliss, especially when it comes to health. Only a few decades ago, the best that genetics could offer was a basis for calculating our statistical chances of being afflicted by a disease or disorder due to a defective gene, of carrying such a gene, or of passing the gene along to our offspring. More recently, paralleling the discovery of genes that cause specific genetic diseases, precise diagnostic methods have emerged. These advances have created opportunities for highly effective detection and diagnosis of genetic disorders—even prenatally—as well as for definitive predictive tests. Particularly important are new procedures enabling us to identify genetic defects that spell potentially life-threatening, future complications (such as cancer or a heart disorder). Predictive or presymptomatic testing is discussed fully in Chapter 24. The point I wish to emphasize here is that knowledge of your family history could prompt a genetic analysis that might enable you not only to save your own life but also the lives of those dear to you.

    Imagine, as you cross a street, seeing a truck barreling down a hill and recognizing that you have no escape. If you had been forewarned and spotted the truck before you entered the crossing, you could have taken evasive action and avoided being hit by the truck. Similarly, if you were standing on a street corner watching a loved one cross the street and you saw the truck bearing down, would you not automatically call out a warning? Lacking any such warning, you would share the desperate sadness I feel when I see patients who have ignored their family history and discovered too late that tests were available that might have been lifesaving. I have repeatedly seen siblings and cousins, uncles and aunts, and even parents whose lives were lost or placed at serious risk because of their failure to pay attention to genetic disorders in their family. It is worse still to communicate the diagnosis of a serious genetic disorder in a child and witness the devastating realization by the parents (and other family members) that one of their own was affected but had failed to warn close relatives about their risks and available tests.

    It may take a great deal of effort to unearth the facts of your family's health history, especially given the dehiscence of modern families. Discord is common in today's families, and full communication—especially about private health matters—is frequently limited or absent. Yet these barriers must be overcome if you are concerned about yourself and your loved ones. You must also overcome the natural fear of finding out that you are affected by or are carrying a culprit gene. Although denial may be helpful as a psychological defense mechanism, it can be a fatal flaw where genetic risks are concerned. Obsessing about potential risk factors is similarly unhelpful because it tends to paralyze us and prevent timely action. The all-important first step is to care enough to become as well informed as possible about your family medical history. This is an ongoing process: You should update the information you have on a regular basis, at least annually (see Chapter 2).


Why You Should Know


Never before in the annals of human history was it possible literally to "know your genes." Now, as a consequence of the Human Genome Project—an international effort to map the structure of all human genes—the location and identification of every human gene is essentially complete. These advances are comparable in significance to the splitting of the atom and walking on moon. They will have a huge impact, because genes play a major role in all matters of health and illness—not only in inherited disorders. Genetic disorders affect at least one person out of every ten living in the Western world. In the United States, over 26 million people are affected by an inherited disorder. Of these, most suffer from diseases caused by the interaction of multiple genetic and environmental factors; many others are directly afflicted by a disease caused by a single gene (such as cystic fibrosis, Huntington's disease, sickle cell disease, and hemophilia).

    Thus far, more than 8,500 genetic diseases or inherited physical or biochemical traits caused by single defective genes have been catalogued. These diseases and conditions account for 25 to 30 percent of admissions to the major children's hospitals in the United States and Canada. Their preponderance in proportion to other causes of hospitalization is partly due to the waning of serious infectious diseases over the past few decades as well as to improved early recognition of genetic disorders and to the increased life span of some of those affected. Moreover, three or four of every 100 babies born have a recognizable major birth defect that may or may not be genetic. By age 7, an additional 3 to 4 percent of children are found to have major birth defects that were not evident when they were newborn. Disorders involving the heart, muscles and ligaments, kidneys, eyes, brain, and skin were among those most often diagnosed at this later stage. Overall, then, between 6 and 8 percent of all children are born with or later manifest major birth defects. In addition, more than 6 million individuals in the United States are mentally retarded due either to hereditary or acquired disorders.

    Clearly, genetic disorders may threaten life or cause all manner of health problems. The key reason to find out as much as you can, as soon as you can, is to obtain timely diagnosis and treatment that may preempt or ameliorate the condition. By knowing your genes, you can save your life: Once you recognize a condition as genetic, you can determine your specific risk, elect precise diagnostic tests, establish careful surveillance by regular testing, and take other preemptive or therapeutic measures (such as elective surgery). The same considerations apply to your children and close family members.

    We are all carriers of some helpful and some harmful genes (see Chapters 6 and 7). Increasingly, it is becoming possible to determine through laboratory testing which defective genes we carry that make us susceptible to common genetic disorders and that increase our risks of having affected children. In this context, it is important to recognize that we all have genes that make us susceptible to specific diseases and to certain environmental agents. These genetic susceptibilities or predispositions may result in illness, allergic reactions, adverse effects of medications, stomach complaints from dietary items (e.g., milk), and even death. The identification of our genetic susceptibilities may provide us opportunities to avoid illness or worse catastrophes (see Chapter 9).


What You Should Know


All aspects of health and illness are both governed by genes and influenced by environmental factors. The vast majority of disorders that affect mankind are due to interactions between genes and environmental agents such as bacteria and viruses, dietary components, and toxins. Topping the list of what you should know are details about your family medical history (see Chapter 2). Ethnic background is also extremely important, as many genetic traits are linked with ethnicity. Indeed, knowledge of your ethnic origin is second in importance only to knowledge of your family medical history. The determination of your genetic risks based on your ethnic origin could prompt specific gene tests enabling you and your family members to avoid a number of disorders (see Chapter 8). You should maintain a family tree (pedigree) chart, updated annually, and request that your physician place a copy in the front of your medical record (which invariably is not the case at present). Unfortunately, a number of laws still exist that impede the access of adoptees to information about their biological parents (see Chapter 26). Such laws must be changed.

    It is important to realize that there is no family without some flawed genes. Recognition of a clearly inherited disorder should lead you first to seek a referral for genetic counseling. This would apply not only to yourself but to all of your family members who could be at risk. Many are unaware that there are Board-certified specialists in clinical genetics who provide genetic diagnoses and counseling. These physician specialists, who are certified by the American Board of Medical Genetics and most of whom are members of the American College of Medical Genetics, are likely to be found in every major university medical center. A consultation with a clinical geneticist could prove the most important step you take in your life.

    If faced with evidence of a genetic disorder in your family, you should make every effort to obtain an accurate diagnosis. Increasingly, the diagnostic process involves analysis of a specific gene. A precise genetic analysis will facilitate an accurate, early diagnosis and give you time to take preemptive steps. It also will permit you and your physician to identify the best means available for monitoring and maintaining your health.


A Responsibility to Tell


The discovery that you harbor a certain genetic defect may have important—even momentous—implications for your personal future plans as well as your present health. But remember also that genes travel: Your children, your parents, grandparents, grandchildren, uncles, aunts, and cousins may also unwittingly be at risk. Each of us has the ethical responsibility to communicate vital information to our relatives, although the choice of whether to act on such knowledge is theirs alone. Sadly, I have repeatedly seen unnecessary illness, genetic defects, and death caused by a lack of communication about such matters within families. Hiding the truth behind a cover of concern for the feelings of individual family members is unacceptable when the wellness and the very life of another is at stake. We have a moral imperative to tell.

    The death of a child due to a grave birth defect or genetic disorder is a painful tragedy that lives on in eternal memory. Years later, when the siblings of such a child are planning their own families, the facts about their deceased sibling become important because of possibly increased risks to their own offspring. Yet well-meaning parents too often fail to tell their children about such tragedies. We prefer to avoid talking about severely retarded, institutionalized relatives, stillbirths, and other family defects that signal increased risks to us. Protectiveness, shame, culpability, superstition, unwillingness to relive the pain in telling, and ignorance of the importance to others of knowing the facts are the main motivating factors I have observed. Families simply must realize their responsibility to tell. Equally important is the need for couples who have had a defective child to inform their siblings, uncles, aunts, and cousins who are still in their childbearing years. Families that care will share their knowledge.


Types of Genetic Disorders


A clear understanding of the different ways harmful genes are transmitted is important (see Chapter 6). Some genetic diseases involve only a single gene, as is the case for Huntington's disease, a progressive brain degeneration that causes dementia, speech defects, and purposeless muscle movements. A single-gene disease, inherited from one parent, is called dominant. Another type involves defects in a pair of genes, as in cystic fibrosis, a disorder that causes chronic lung infection and malabsorption of food. This recessive disorder is transmitted equally by two parents who are completely healthy and who usually are not even aware that they carry this condition in their genes. Sex-linked disorders involve single genes that cause diseases that mainly (but not exclusively) affect males. Hemophilia, a bleeding disorder caused by a missing blood clotting factor, is linked to a defective gene transmitted by females but occurring almost exclusively in males. The remarkable mitochondrial inheritance is due to defects in genes that congregate in tiny structures called mitochondria, which are dispersed in the cell fluid around the nucleus. The entire set of genes in mitochondria originates from the mother. A few, rare genetic conditions are due to mitochondrial malfunction. In such cases, a mother would transmit the disease to all of her children.

    Genetic disorders that result from the interaction of multiple genes with one or more environmental factors are called multifactorial or polygenic. Examples include high blood pressure, coronary heart disease, schizophrenia, and many other conditions discussed in this book.

    Major birth defects, including mental retardation, may arise as a consequence of defects in the development of cells in the early embryo. Such defects include heart malformations (such as a hole in the heart, called ventricular septal defect), an open spine defect (called spina bifida), a cleft lip and palate, and hundreds of others. Defects such as these may occur as the result of the failure of cells to migrate, to organize into defined tissues, to differentiate into specialized cell functions, or even to die when programmed to do so. A whole panoply of environmental factors (including diet, infectious agents, toxins, and medications) may by themselves, or through interaction with our genes, result in such defects (see Chapter 9). These disorders may be present at birth (called congenital) and could be due to environmental factors alone or to the interaction of such factors with our genes. You will obtain a clearer understanding of the various ways in which genetic disorders and birth defects occur from the chapters that follow.


Good Genes, Bad Genes


The oft-heard compliment regarding "good genes" invariably refers to admirable qualities and characteristics that a person might have inherited from a parent or grandparent. While it might be wishful thinking to have a category of "good" genes, we would all like to think that these genes are "healthful," enabling, and protective. "Healthful" genes might be those that help us maintain and achieve good physical and mental health with at least average intellectual capacity. Such genes probably do exist but almost invariably can be expected to function through close interactions with environmental influences, which include family and the physical environment. "Good" genes may also enable superior performance—physical, artistic, musical, and intellectual. Remember the Swiss Bernoulli family of mathematicians, in which there were three generations with eight mathematicians of unusual ability and more than 120 descendants, the majority of whom achieved distinction. "Good" genes might also be expected to be protective—for example, against infections or even cancers. Genes that govern the veritable army of immune mechanisms warding off environmental insults to our bodies are in this group: the genes that orchestrate antibodies, white blood cell functions, tissue repair systems, and many other protective mechanisms.

    "Bad" or disadvantageous genes include those that are structurally defective and that lead directly to diseases as well as those that act in concert to produce only dysfunction. Much of this book is about the importance of recognizing and detecting genes that, make us susceptible to specific diseases or predispose us to react in ways that endanger our lives or health. Detection of a defective "mutated" gene could be the key tip-off that could save your life. For example, there is a single gene that, when defective, predisposes an individual to develop alarmingly high temperatures (for example, 108°F) while undergoing a routine surgical operation under anesthesia. Deaths on the operating table from malignant hyperthermia are well known but thankfully rare and treatable if detected immediately. Many culprit genes predispose our bodies to react adversely—sometimes even with fatal consequences—to medications we may take or environmental factors to which we may be exposed. Examples abound. Allergy to penicillin on rare occasions might be so overwhelming as to be fatal (anaphylaxis). When exposed to sulfa medications or certain other drugs, those born with an enzyme deficiency called glucose-6-phosphate dehydrogenase (G6PD) are particularly likely to develop serious hemolytic anemia (in which the life span of circulating red blood cells is dramatically shortened). Remarkably, disadvantageous genes may also confer benefits. Carriers of the sickle cell disease gene have been shown to be more resistant to malaria. The same can be said for female carriers of the sex-linked G6PD deficiency.


It's All in the Genes


Have you ever realized how unique you are among the more than 6 billion people that inhabit the earth? Unless you are an identical twin (or an extremely rare identical triplet), it is unlikely you will encounter anyone else with a genetic makeup identical to your own. Even more remarkable is the astounding realization that humans share 99.9 percent of their genes and at least 98.5 percent with chimpanzees. There must therefore only be a mere handful of genes that enable us to walk upright, compose music, reason, and make moral distinctions. We do not yet understand the precise differences in genes between humans and chimpanzees. But this question is of more than rhetorical interest, because apes are less susceptible than humans to diseases such as cancer and AIDS. Biochemical differences between humans and apes are being discovered and work is in progress to define the genetic origins of the two species. Early results indicate that a certain type of sugar (sialic acid) is missing from the surfaces of all human cells. This molecule may play a variety of roles. For example, it may influence the communication pathways used by genes to regulate an infinite number of functions.

    The number of actual and potential interactions and communications within and between the cells of an organism is infinite. Common sense would suggest that similar cell functions must be necessary to maintain life in any species. Since we know that all bodily functions and structures are dictated by genes, it should come as no surprise that key genes responsible for fundamental life-maintenance functions in humans are also present in even the most primitive of species. Advances in biotechnology have shown that many genes common to species such as zebra fish, frogs, worms, and fruit flies have been conserved in humans and other mammals (e.g., mice and other rodents, pigs, and other species). We now know that highly conserved genes—for instance, those found even in the zebra fish or frog—when occurring in mutant form in humans can cause serious and even fatal disorders. This knowledge of gene conservation has been valuable in the detection of human genes. For example, once our team had identified a gene responsible for pigmentary and other anomalies in mice, we were able to locate a comparable (syntenic) region on human chromosome 2 and discover a gene that causes a disorder called Waardenburg syndrome (characterized by variable presence of deafness, a white forelock, eyes of different color, patchy hypopigmentation, and wide-set eyes).


The Gene Orchestra


Like the instruments in a large symphony orchestra, not all genes are in action simultaneously. Many genes function only for a few hours or days before switching off, never to function again. Such genes play critical roles—for example, in directing how the sperm fertilizes the egg, or in the early stages of the embryo, dictating the timing of cell replication, organization, migration into defined regions, and differentiation into specialized tissues and organs. Many genes participate in these many stages, but only briefly. Later in life, there are occasions (for example, when the body is threatened by certain types of cancer) when some embryonic genes turn on again and even begin manufacturing embryonic proteins.

    Imagine for a moment the orchestra of genes necessary to create and run the human heart. Structural genes are responsible for influencing primitive embryonic cells into becoming the genetically predestined specialized cells of the heart muscle, capable of producing rhythmic beats for a lifetime. Other genes meanwhile simultaneously are forming and organizing the inner lining of the heart and the cement (fibrous collagen tissue) that holds all of these cells together. In another orchestral section, other genes are responsible for developing and laying out the coronary arteries and their branches as well as their inner linings and vessel wall structure. Synchronized, harmonious gene action is vital to ensure that the inner lining of the coronary arteries, the collagen and muscle of the arteries and veins, and the connections between their tributaries are formed and integrated. In simultaneous but separate action, another set of genes functions to develop and thread the key nerves that convey the electrical impulses controlling the heartbeat. The geography of the coronary arteries, and even the electrocardiogram, directly reflect the functions of genes. Defects in any one of these critical genes may result in fatal genetic diseases of the heart muscle (cardiomyopathy) or inherited disturbances of heart rhythm (arrhythmias) like those that have caused the deaths of various famous sports figures on the court or the playing field. Genes even dictate that the heart be positioned on the left side. When these so-called laterality genes are defective, the heart could fail to rotate, remaining instead on the right side of the chest. The same (and possibly other) laterality genes can reverse the positions of the spleen and liver.


This brief introduction serves as a broad outline of why and what you should know about your genes, and the importance of this knowledge to you and your loved ones. This early preview of the complex nature of gene function sets the stage for more detailed discussions. Remember, to know is to care, and caring takes effort.

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Table of Contents

Preface xiii
Acknowledgments xvii
KNOWLEDGE IS LIFESAVING
1 What You Should Know and Why 3
2 Personal Considerations and Your Family History 12
THE THREADS OF YOUR LIFE
3 Too Many or Too Few Chromosomes 23
4 Sex Chromosome Disorders 37
5 Chromosome Rearrangements 45
6 Genes 55
7 You and Your Genes 66
8 Ethnic Genes and the Disorders They Cause 85
9 When Threads or Blueprints Go Awry: Mental Retardation
and Birth Defects 98
10 Genes That Make You Susceptible to Various Disorders
or Complications 119
HARMFUL GENES
11 Genes and Heart Disease 143
12 Genetic Disorders of Heart Structure Rhythm, and of
the Arteries 158
13 Is High (or Low) Blood Pressure Inherited? 172
14 Genes and Diabetes 178
15 Obesity: Genes or Environment? 193
16 Genes and Cancer 203
17 Is There a History of Cancer in Your Family? 211
18 Mental Illness in the Family:Schizophrenia 240
19 Genes, Depression and other Mood Disorders 250
20 Genes and Alzheimer's Disease 259
21 Genes, Aging, and Longevity 270
AVOIDANCE AND PREVENTION OF GENETIC DISORDERS
22 Prenatal Diagnosis of Genetic Disorders 283
23 Genetic Disorders and Pregnancy 300
PERSONAL MATTERS, PREDICTIVE TESTS, GENETIC COUNSELING, AND TREATMENT
24 Presymptomatic and Predictive Genetic Diagnosis 309
25 Genetic Counseling 323
26 Genes, Ethics, Law, and Public Policy 331
27 Treatment of Genetic Disorders 349
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