GOOD HEALTH MAGAZINE : MEDICINE : COMING TO GRIPS WITH HEREDITY : SCIENTISTS ARE CREATING A DETAILED ROAD MAP OF THE ENTIRE HUMAN GENE SYSTEM, AND THERE IS NOW A REALISTIC POSSIBILITY THAT MEDICAL ADVANCES MAY GENERATE NEW TREATMENTS FOR GENETIC DISORDERS
Few families are not affected in some way by genetic disorders, whether a crippling and devastating disease such as cystic fibrosis, a chronic condition like high blood pressure or a predisposition to alcoholism or mental illness. Yet most of us know very little about genetic diseases--what they are, how they are transmitted, how they may be screened or treated, even how to find information about them. Indeed, few of us know whether we or our children are at risk from such afflictions.
While geneticists have long been interested in genealogy, and genealogists in genetics, only recently have the two fields become linked in a way that promises dramatic advances in our understanding of the relationship between genetic disorders and ancestry.
For the first time there is a realistic possibility that medical advances eventually may correct, cure or result in new treatments for genetic disorders. Today, new methods of genetic detection and advances towards various forms of gene therapy offer hope.
U.S. scientists plan to create a detailed road map of the entire human gene system that they hope will lead to improved diagnosis of hereditary diseases, development of new drugs and an assortment of unforeseen benefits. There is great enthusiasm for the project. It would make possible the mapping of genes responsible for muscular dystrophy, neurofibromatosis and the genetic sequences related to manic depression. Only recently, with the development of specialized automated technologies, has a high-resolution map showing every human gene become feasible.
If you are like most people, you probably think that genetic diseases are rare. Although it is true that each of the more than 3,000 genetic disorders is relatively rare, taken as a group they are quite common. Innumerable people suffer from conditions due wholly or in part to defective genes or chromosomes. For example:
Between 12 million and 15 million Americans have a genetic disorder of one kind or another.
A total of 20 million Americans are carriers of true genetic defects.
One of every 250 newborn babies has a genetic disorder.
One of every three babies or young children admitted to a hospital is there because of a genetic problem.
Each of us carries an average of between four and seven abnormal recessive genes that do not affect us but may cause disease in our offspring.
MOREOVER, IT IS now recognized that the major cripplers and killers of adults--diabetes, heart disease, various psychiatric illnesses and some cancers--all have significant genetic components. Current genetics research in these and other areas is blazing frontiers almost undreamed of a generation ago.
The human genetics revolution is providing precise information on who is most vulnerable to what kind of illness and who particularly should avoid certain environmental agents. It is providing fresh insights into the function of regulatory genes that affect all human growth and development, from birth to death.
As scientists discover the genetic risk factors of certain diseases, people who find that they are susceptible may be able to reduce their chances of illness simply by altering specific aspects of their behavior and environment. As research advances, it is enabling doctors to help millions of people control or prevent inherited diseases, including some diseases that have been identified only in the past 20 years.
The recent wave of genetic research has already brought about the following discoveries:
Research continues on human gene therapy in which doctors transplant copies of a normal gene into the cells of a patient whose own body lacks the gene or has it in an abnormal form. Eventually, this process may be used to effectively treat patients with cystic fibrosis, various forms of hemophilia and possibly muscular dystrophy.
A genetic test, still in a preliminary state, has been devised for a kidney disease that affects about 400,000 Americans and is responsible for one in 10 kidney-dialysis patients. This test would enable doctors to diagnose the disease before symptoms appear, which is usually in middle age. The affliction, polycystic kidney disease, is a dominant disorder, meaning that those who carry the disease gene will pass it on to half of their children, who will then develop the condition.
Scientists have developed a simple blood test to diagnose alcoholism that may offer a way to screen people to see if they have inherited a risk of alcoholism.
Although a long way from solution, sickle-cell anemia, common in blacks, and Cooley’s anemia--common in Greeks, Italians and others of Mediterranean descent--may some day be treatable as a result of work now in progress. Scientists have developed a faster method to detect the defective genes responsible for these disorders.
Doctors are able to use a new genetic test to tell couples what their chances are of having a child with Duchenne muscular dystrophy, a fatal disease. The technique can also track through families the faulty genes that causes cystic fibrosis and 10 other inherited diseases.
Scientists have identified the genetic defect responsible for Gaucher’s disease, a rare disorder that most commonly affects Jews of Eastern European descent. The encouraging findings should improve testing for the disease and may eventually lead to a treatment.
In a major advance toward human gene therapy, research scientists late in 1988 successfully transplanted new genes into animal cells at the precise locations of defective ones, and the healthy genes replaced or repaired the old. That research has brightened the prospects for treating fatal hereditary illnesses such as sickle-cell anemia and cystic fibrosis at the genetic level.
THIS GENETICS revolution is already affecting your life, whether you realize it or not. The family doctor who once took your family health history by asking what childhood diseases you had, and whether your parents or grandparents had suffered from diabetes or heart disease, has expanded the medical pedigree. The doctor now asks questions about your ethnic origins, dates and causes of death of all four grandparents, and the kinds of diseases suffered by other relatives.
Most of us are not sufficiently knowledgeable about the medical histories of our relatives. And simply knowing the cause of death of family members is not enough, for your grandfather may have died of what was termed “old age” on his death certificate, but he may also have suffered from diabetes or arthritis, which may have been the primary reason for his decline. As the science of genetics becomes even more refined in future years, the recording of comprehensive and well-documented family health histories will be a necessity if grandchildren and great-grandchildren and later generations are to benefit.
In addition to enhancing the accuracy of diagnosis, a complete family health history is necessary for effective genetic counseling. Such counseling concerns itself not only with the probability of other family members being affected but also with aspects of prognosis, treatment and emotional adjustment.
You needn’t become a genealogist to compile a medical pedigree; concern yourself only with gaining accurate medical information about your families as far back as your four grandparents and the siblings in each generation. But you will need to do this on your spouse’s side of the family as well to provide your children with a complete family-health tree.
The major records you need to locate, analyze and compile for a medical pedigree include death certificates, newspaper obituaries, insurance company records, hospital records, medical records, census records, mortality schedules, military records.
Once you have obtained information, compile it, listing your ancestors’ names, dates of death, ages and causes of death. The compilation often reveals patterns. You may discover that on your father’s side most of your ancestors died of heart-related disease and that on your mother’s side cancer was prevalent. Or you may discover that most of your family died simply of “old age” or accidental causes.
To get an overview of what your family’s medical history looks like, construct a chart to show family members’ ages at death and their major health problems and causes of death. It is often difficult to determine genetic disorders in a family without the aid of a geneticist, but for most purposes what is important is to record the various diseases that have plagued your family over the years. That can serve to alert family members to their predisposition toward certain health problems. The resulting information should be given to all family members so they can share it with their family doctors.
There are genetic diseases that are characteristically found in one group and not in the others. For example, if you are of Jewish origin, your doctor should know whether you descend from Sephardic, Oriental or Ashkenazi ancestors. Frequently, it is necessary to examine numerous members of a patient’s family before diagnosis of a genetic disorder can be made with certainty.
A thorough history is crucial if you are about to start a family. You should always be concerned about the presence of congenital anomalies in your family, as well as the clustering of any traits or diseases, and should tell your doctor about them.
Determining a genetic link for a disease can be extremely complex, especially where one inherits the disorder through a recessive gene. Individuals affected with a recessive diseases will often find no pattern or precedent for the disease in their family history. You yourself may not suffer any medical problems stemming from it, but if your spouse also carries the same recessive gene, the disorder can manifest itself in your children or show up in your grandchildren--provided that your children’s spouses have the same recessive gene.
It is believed that genetic factors may be involved in 25% of diseases. Frightening as that figure is, many genetic disorders once thought to be incurable can now be controlled or treated successfully if they are diagnosed early.
Moreover, within the next 10 years, scientists expect to identify between 2,000 and 3,000 genetic markers--which indicate a defective gene is present in a particular site on a chromosome--that could lead to predictive tests for thousands of illnesses, from stroke to heart attack and cancer to Alzheimer’s disease.
You probably know that hemophilia, sickle-cell anemia and cystic fibrosis are genetic diseases, but do you know that obesity, some forms of cancer, some forms of early heart disease, and some blindness, deafness and birth defects are inheritable? Some genetic disorders are very rare, but others, such as diabetes, are among the most common illnesses.
There are four mechanisms by which genetic defects may be transmitted from one generation to another: (1) autosomal dominant inheritance, where the trait is inherited from one parent and from the previous generation; (2) recessive inheritance, where both parents are unaffected; (3) X-linked (or sex-linked) inheritance, in which the gene for the characteristic is known to be on the X chromosome, and (4) multifactorial inheritance patterns.
Autosomal Dominant Inheritance: Autosomal means that the gene pair is present in a chromosome pair other than the sex chromosomes. Chromosomes are threadlike structures within the nuclei of cells that carry the inherited genetic information that directs the growth and functioning of the entire body. In dominant inheritance an affected child usually has a parent with the same disorder. When a parent has a dominant gene for a disease, there is a 50% risk that each child will manifest the defect, although it may not be evident at birth. Among the 2,000 confirmed or suspected autosomal dominant disorders are: Huntington’s disease polydactyl (extra fingers or toes), achondroplasia (a form of dwarfism), chronic simple glaucoma (some forms), hypercholesterolemia ((high blood cholesterol levels, with propensity to heart disease).
Recessive Inheritance : Both parents of an affected child appear essentially normal, but by chance both may carry the same harmful gene, although neither may be aware of it. Recessive inherited diseases tend to be severe and often cause early death. When both parents are carriers of a harmful recessive trait, each of their children will run a 25% risk of manifesting that genetic disease, and each has a 50-50 chance of receiving only a single defective gene and becoming a clinically normal carrier of the genetic trait, like the parents. The chance of inheriting a recessive disorder is increased in a child whose parents are consanguineous (blood related).
Among the more than 1,000 confirmed or suspected autosomal recessive disorders are: cystic fibrosis, galactosemia, phenylketonuria, sickle-cell disease, thalassemia, Tay-Sachs disease, Gaucher’s disease.
X-Linked (also called sex-linked) Inheritance: In X-linked inheritance, a clinically normal mother carries a faulty gene on one of her X chromosomes. Each son has a 50-50 chance of inheriting that gene and manifesting the disorder. Each of her daughters has an equal chance of being a carrier, like her mother, and is usually unaffected by the disease but capable of transmitting it to her sons. No male-to-male transmission of X-linked disorders can occur--that is, a father cannot pass the disorder on to his son.
Among the some 250 confirmed or suspected disorders transmitted by a gene or genes on the X chromosome are: colorblindness, hemophilia, agammaglobulinemia (lack of immunity to infections), muscular dystrophy (some forms), spinal ataxia (some forms).
Multifactorial inheritance: The pattern of transmission in this group is less well-defined, but these genetic disorders result from the interaction of many genes and with other genes or with environmental factors. Thought to be multifactorial are: cleft lip and/or palate, clubfoot, congenital dislocation of the hip, spina bifida, hydrocephalus (water on the brain, occurring with spina bifida), pyloric stenosis (narrowed or obstructed opening from the stomach into the small intestine), congenital heart defects, diabetes mellitus (abnormal sugar metabolism).
Certain genetic diseases are widespread in the population; others, such as sickle-cell anemia and Cooley’s anemia, primarily affect certain ethnic or racial groups. Cystic fibrosis is one of the most common genetic diseases among Americans because it largely affects whites of Northern and Western European ancestry. Tay-Sachs disease is a recessive-gene disorder that often strikes infants of Central and Eastern European Jewish descent.
The major diseases that strike American families today--heart disease, cancer and diabetes--all show a tendency to “run in families.” That does not mean you are doomed to have one of them if a parent or relative suffered from the condition, but you should be aware of the risks where there is a precedent for the disease.
Early heart attacks do run in families. If you have a relative who had a heart attack before reaching 65, your risk of having one before that age is five to seven times the normal risk for your sex. Moreover, some of the leading factors known to contribute to coronary disease--high cholesterol levels, high blood pressure, diabetes and obesity--have been found to have a genetic link.
Several types of cancer are known to be directly inherited, such as retinoblastoma of the eye. There are common forms of cancer that tend to run in families--stomach, endometrium (uterine lining), lung, colon, bladder and breast cancer and malignant melanoma of the skin.
Researchers have established recently that you are likely to develop Type II, or non-insulin-dependent, diabetes, the most common form of this disease, if one or both parents have it.
What good does it do to know if you are at risk for a genetic disease? People who know about a predisposition toward a disease can do a lot to prevent that disease, either by changing high-risk behavior or by detecting health problems early. If you are alerted to the genetic liabilities you carry, you can develop corrective habits, or at least be treated at the earliest possible stage.
The March of Dimes Birth Defects Foundations recommends genetic counseling if you or family members have a disease with a genetic component; if you are a member of an ethnic group with a high risk of certain genetic diseases; if you have produced an affected child; if you are an expectant mother 35 years of age or older.
HOW RECESSIVE INHERITANCE WORKS
Both parents, usually unaffected, carry a normal gene (N) that takes precedence over its faulty recessive counterpart (r).
CARRIER FATHER: CARRIER MOTHER
The odds for each child are:
1. A 25% risk of inheriting a “double dose” of r genes which may cause serious birth defects.
2. A 25% chance of inheriting two Ns, thus being unaffected.
3. A 50% chance of being a carrier, as both parents are.
HOW X-LINKED INHERITANCE WORKS
In the most common form, the female sex chromosomes of an unaffected mother carry one faulty gene (X) and one normal gene (x). The father has normal x and y chromosome complement.
CARRIER MOTHER: NORMAL FATHER
The odds for each male child are:
1. A 50% risk of inheriting the faulty X and the disorder.
2. A 50% chance of inheriting normal x and y chromosomes.
The odds for each female child are:
1. A 50% risk of inheriting one faulty X, to be a carrier like the mother.
2. A 50% chance of inheriting no faulty gene.
HOW DOMINANT INHERITANCE WORKS
One affected parent has a single faulty gene (D) that dominates its normal counterpart (n).
AFFECTED FATHER: NORMAL MOTHER
Each child’s chance of inheriting the D or the n is 50%.
