Genetics and Health - Common Genetically Inherited Diseases

sickle cell cells scd

Although many diseases, disorders, and conditions are termed "genetic," classifying a disease as genetic simply means that there is an identified genetic component to either its origin or expression. Many medical geneticists contend that the majority of diseases cannot be classified as strictly genetic or environmental. Environmental factors can greatly influence the way disease causing genes express themselves. They can even prevent the genes from being expressed at all. Similarly, environmental (infectious) diseases may not be expressed because of some genetic predisposition to immunity. Each disease, in each individual, exists along a continuum between a genetic disease and an environmental disease.

A multitude of diseases are believed to have strong genetic contributions, including:

  • Heart disease—coronary atherosclerosis, hypertension (high blood pressure), and hyperlipidemia (elevated blood levels of cholesterol and other lipids)
  • Diabetes
  • Cancer—retinoblastomas, colon, stomach, ovarian, uterine, lung, bladder, breast, skin (melanoma), pancreatic, and prostate
  • Neurological disorders—Alzheimer's disease, amyotrophic lateral sclerosis (also known as Lou Gehrig's disease), Gaucher's disease, Huntington's disease, multiple sclerosis, narcolepsy, neurofibromatosis, Parkinson's disease, Tay-Sachs disease, and Tourette's syndrome
  • Mental illnesses, mental retardation, and behavioral conditions—alcoholism, anxiety disorders, attention deficit hyperactivity disorder, eating disorders, Lesch-Nyhan syndrome, manic depression, and schizophrenia
  • Other disorders—cleft lip and cleft palate, clubfoot, cystic fibrosis, Duchenne muscular dystrophy, glucose galactose malabsorption, hemophilia, Hurler's syndrome, Marfan's syndrome, phenylketonuria, sickle cell disease, and thalassemia
  • Medical and physical conditions with genetic links—alpha-1-antitrypsin, arthritis, asthma, baldness, congenital adrenal hyperplasia, migraine headaches, obesity, periodontal disease, porphyria, and selected speech disorders

Cystic Fibrosis

Cystic fibrosis (sometimes referred to as CF) is the most common inherited fatal disease of children and young adults in the United States. According to the Merck Manual of Diagnosis and Therapy (17th edition, 1999,, it occurs in about one in every three thousand Caucasian births, one in fifteen thousand African-Americans, and one in thirty-two thousand Asian-Americans. According to the Cystic Fibrosis Foundation (, in 2006 an estimated thirty thousand young people had the disease; their median life span (half of this population were above and half were below) is thirty-seven years. An estimated twelve million Americans (one in twenty-five), almost all of whom are white, are symptomless carriers of the CF gene. Like sickle cell disease, it is a recessive genetic disorder—in order to inherit this disease, a child must receive the CF gene from both parents.

In 1989 the CF gene was identified and in 1991 it was cloned and sequenced. The gene was called cystic fibrosis transmembrane conductance regulator (CFTR) because it was discovered to encode a membrane protein that controls the transit of chloride ions across the plasma membrane of cells. Nearly one thousand mutations of the large gene have been identified. Though most are extremely rare, several account for more than two-thirds of all mutations. The mutated versions of the gene found in persons with CF were found to cause relatively modest impairment of chloride transport in cells. Chloride transport is critical because chloride is a component of salt involved in fluid absorption and volume regulation, and this seemingly minor defect can result in a multisystem disease that affects organs and tissues throughout the body, provoking abnormal, thick secretions from glands and epithelial cells. Eventually, sticky mucus fills the lungs and pancreas, causing difficulty in breathing and interference with digestion; ultimately, affected children die of respiratory failure.

At first, a child with CF does not appear to be suffering from a serious illness, but the diagnosis is usually made by the age of three. Often the only signs are a persistent cough, a large appetite but poor weight gain, an extremely salty taste to the skin, and large, foul-smelling bowel movements. A simple "sweat test" is currently the standard diagnostic test for CF. The test measures the amount of salt in the sweat; abnormally high levels are the hallmark of CF.


In August 1989 researchers isolated the specific gene that causes CF. The mutation of this gene accounts for about 70% of the cases of the disease. In 1990 scientists successfully corrected the biochemical defect by inserting a healthy gene into diseased cells grown in the laboratory, a major step toward developing new therapies for the disease. In 1992 they injected healthy genes into laboratory rats by using a deactivated common cold virus as the delivery agent. The rats began to manufacture the missing protein, which regulates the chloride and sodium in the tissues, preventing the deadly buildup of mucus. Scientists were hopeful that within a few years CF would be eliminated as a fatal disease, giving many children the chance for healthy, normal lives.

In 1993, however, optimism faded when the medical community discovered that the CF gene was more complicated than expected. Scientists found that the gene can be mutated at more than 950 points, and more points were appearing at an alarming rate. At the same time, they discovered that many people who have inherited mutated genes from both parents do not have CF. With so many possible mutations, the potential combinations in a person who inherits one gene from each parent are immeasurable.

The combinations of different mutations create different effects. Some may result in crippling and fatal CF, while others may cause less serious disorders, such as infertility, asthma, or chronic bronchitis. To further complicate the picture, other genes can alter the way different mutations of the CF gene affect the body.

In 2006 the Cystic Fibrosis Foundation continued to support clinical research studies in human gene therapy. Several studies are using the adenovirus rather than the common cold virus as the vehicle for delivering healthy genes to lung or nasal tissue. Another study is using liposomes (fat cells) as a delivery vehicle. Still another form of gene therapy uses a compacted DNA technology. The goal is for the DNA to produce the CFTR protein that is needed to correct the basic defect in CF cells.

Researchers are also finding more evidence that CF mutations may be much more common than previously thought. For example, five thousand healthy women receiving prenatal care at Kaiser Permanente in northern California were tested for the CF gene, thought to be present in less than 1% of the population. Of those screened, 11% had the mutation. This finding may indicate that many more common diseases, such as asthma, may be caused by mutations of the CF gene. Other scientists have speculated that the frequency of CF carriers among persons of European descent may have, at some point in time, conferred immunity to some other disorder, in much the same way that sickle cell carriers were found to be protected from contracting malaria.


Because there is a relatively high frequency of carriers of the defective gene in the general population, in 2000 the NIH, the American College of Medical Genetics, and the American College of Obstetricians and Gynecologists issued a recommendation that CF screening be offered to every white woman who is pregnant or considering having a baby. However, the results of several research studies have found that many people who carry the CF gene fail to inform family members about their risk ("Genetic Testing for Cystic Fibrosis: National Institutes of Health Consensus Development Conference Statement on Genetic Testing for Cystic Fibrosis," Archives of Internal Medicine, vol. 159, no. 14, July 26, 1999).

The investigators and other health educators believe that if carriers were better informed about their risks they might be more likely to disclose them. Pretest education and counseling were seen as key to increasing carriers' understanding of the significance of findings and their family planning options. For example, when both parents are carriers, the risk of their child having CF is one in four, and the risk of their child being a carrier is one in two. When both parents are carriers, they may choose to have prenatal diagnosis using CVS or amniocentesis to find out whether their unborn child will have the disease. Alternatively, they may choose to use assisted reproductive technology such as in vitro fertilization (the egg and sperm are united outside of the body), because it offers the option of preimplantation diagnosis. Preimplantation genetic diagnosis enables parents undergoing in vitro fertilization to screen an embryo for CF genetic mutations before it is implanted in the uterus.

Huntington's Disease

Named for the American physician George Sumner Huntington (1850–1916), Huntington's disease (HD), or Huntington's chorea, is an inherited, progressive brain disorder. It causes the degeneration of cells in the basal ganglia, a pair of nerve clusters deep in the brain that affect both the body and the mind. HD is caused by a single dominant gene that affects men and women of all races and ethnic groups.

The gene mutation that produces HD was mapped to chromosome 4 in 1983 and cloned in 1993. The mutation is in the DNA that codes for the protein huntingtin. The number of repeated triplets of nucleotides—cytosine (C), thymine (T), and guanine (G), known as CTG (nucleotides are nitrogen-containing molecules that link together to form strands of DNA and RNA)—is inversely related to the age when the individual first experiences symptoms: the more repeated triplets, the younger the age of onset of the disease. Like myotonic dystrophy, in which the symptoms of the disease often increase in severity from one generation to the next, the unstable triplet repeat sequence can lengthen from one generation to the next, with a resultant decrease in the age when symptoms first appear.

HD does not usually strike until mid-adulthood, between ages thirty and fifty, although there is a juvenile form that can affect children and adolescents. Early symptoms, such as forgetfulness, a lack of muscle coordination, or a loss of balance, are often ignored, delaying the diagnosis. The disease gradually takes its toll over a ten- to twenty-five-year period.

Within a few years, characteristic involuntary movement (chorea) of the body, limbs, and facial muscles appears. As HD progresses, speech becomes slurred and swallowing becomes difficult. The patients' cognitive abilities decline and there are distinct personality changes—depression and withdrawal, sometimes countered with euphoria. Eventually, nearly all patients must be institutionalized, and they usually die as a result of choking or infections.


HD, once considered rare, is now recognized as one of the more common hereditary diseases. According to the National Institute of Neurological Disorders and Stroke (, HD is known to affect about thirty thousand Americans; another one hundred and fifty thousand are at a 50% risk of inheriting it from an affected parent. Estimates of its prevalence are about one in ten thousand persons.


In 1983 researchers identified a DNA marker that made it possible to offer a test to determine, before symptoms appear, whether an individual has inherited the HD gene. In some cases it is even possible to make a prenatal diagnosis on the unborn child. Many people, however, prefer not to know whether or not they carry the defective gene.

For those who have had testing for HD, a positive result rarely brings shock or denial, according to those who conduct pre- and posttest counseling. Most people who learn that they will eventually develop the disease are upset, but there is an acceptance of their fate. Among those whose tests come back negative, there is often a newfound freedom. They are more willing to set goals and enjoy life.


In July 2005 researchers at Johns Hopkins University School of Medicine reported the discovery of a key regulatory molecule whose overactivation by the abnormal protein produced in HD causes the characteristic symptoms of the disease. The abnormal HD protein activates the regulatory protein called p53, which in turn switches on a host of other genes. This abnormal gene activation causes the cells' mitochondria to malfunction, and kills brain cells (Akira Sawa et al., "p53 Mediates Cellular Dysfunction and Behavioral Abnormalities in Huntington's Disease," Neuron, vol. 47, July 7, 2005).

In November 2005 Professor Marina Lynch and her associates from the Institute of Neuroscience at Trinity College in Dublin reported at the 35th Annual Society for Neuroscience Meeting in Washington, D.C., that use of a neuro anti-inflammatory drug called Miraxion appeared to protect the brain from inflammation often associated with a number of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. The investigators assert that determining exactly how Miraxion functions in the brain and establishing its neuroprotective effects is fundamental to improving understanding of its mechanism of action in neurodegenerative diseases ("Amarin Announces Significant Neuroprotective Effects of Miraxion,"

Muscular Dystrophy

Muscular dystrophy (MD) is a term that applies to a group of hereditary muscle-destroying disorders. According to the Muscular Dystrophy Association (MDA;, in 2006 some type of MD affected approximately one million Americans. Each variant of the disease is caused by defects in the genes that play important roles in the growth and development of muscles. In MD the proteins produced by the defective genes are abnormal, causing the muscles to waste away. Unable to function properly, the muscle cells die and are replaced by fat and connective tissue. The symptoms of MD may not be noticed until as much as 50% of the muscle tissue has been affected.

All of the various disorders labeled MD cause progressive weakening and wasting of muscle tissues. They vary, however, in the usual age at the onset of symptoms, rate of progression, and initial group of muscles affected. The most common childhood type, Duchenne MD, affects young boys, who show symptoms in early childhood and usually die from respiratory weakness or damage to the heart before adulthood. The gene is passed from the mother to her children. Females who inherit the defective gene generally do not manifest symptoms—they become carriers of the defective genes, and their children have a 50% chance of inheriting the disease. Other forms of MD manifest later in life and are usually not fatal.

In 1992 scientists discovered the defect in the gene that causes myotonic dystrophy, the most common adult form of MD. In people with this disorder, a segment of the gene is enlarged and unstable. This finding helps physicians more accurately diagnose myotonic dystrophy. Researchers since have identified genes linked to other types of MD, including Duchenne MD, Becker MD, limb-girdle MD, and Emery-Dreifuss MD.

In January 2005 researchers from the Mayo Clinic in Rochester, Minnesota, identified a new form of muscular dystrophy that involves mutations in a protein called ZASP, which binds to cardiac (heart) and skeletal muscles. The researchers detected ZASP mutations in eleven patients; in seven of these, they observed a dominant pattern of inheritance (Duygu Selcen and Andrew G. Engel, "Mutations in ZASP Define a Novel Form of Muscular Dystrophy in Humans," Annals of Neurology, vol. 57, February 2005).


There is no cure for MD, but patients can be made more comfortable and functional by a combination of physical therapy, exercise programs, and orthopedic devices (special shoes, braces, or powered wheelchairs) that help them to maintain mobility and independence as long as possible.

Genetic research offers hope of finding effective treatments, and even cures, for these diseases. Gene therapy experiments specifically aimed toward a cure or a treatment for one or more of these types of MD are under way. Research teams have identified the crucial proteins produced by these genes, such as dystrophin, beta sarcoglyan, gamma sarcoglyan, and adhalin.

Because defective or absent proteins cause MD, researchers hope that experimental treatments to transplant normal muscle cells into wasting muscles will replace the diseased cells. Muscle cells, unlike other cells in the body, fuse together to become giant cells. Scientists hope that if cells with healthy genes can be introduced into the muscles and accepted by the body's immune system, the muscle cells will then begin to produce the missing proteins.

New delivery methods called vectors also are being tested, which involves implanting a healthy gene into a virus that has been stripped of all of its harmful properties and then injecting the modified virus into a patient. Researchers hope this will reduce the amount of rejection by the patient's immune system, allowing the healthy gene to restore the missing muscle protein.

At a November 2005 conference sponsored by the MDA and the University of Arizona College of Medicine, investigators described how the study of the genes involved in MD and development of new methods for pinpointing each patient's precise mutation guided development of molecular strategies for the treatment of Duchenne MD. PTC Therapeutics, a biotechnology company in New Jersey, with support from the MDA, has developed an experimental drug called PTC124 that has proven safe in preliminary human trials ("MDA Gathers Scientists, Physicians for Updates on Research Progress," MDA Research News, December 8, 2005,

Sickle Cell Disease

Sickle cell disease (SCD) is a group of hereditary diseases, including sickle cell anemia and sickle B-thalassemia, in which the red blood cells contain an abnormal hemoglobin, termed hemoglobin S. Hemoglobin S is responsible for the premature destruction of red blood cells, or hemolysis. In addition, it causes the red cells to become deformed, actually taking on a sickle shape, particularly in parts of the body where the amount of oxygen is relatively low. These abnormally shaped cells cannot travel smoothly through the smaller blood vessels and capillaries. They tend to clog the vessels and prevent blood from reaching vital tissues. This blockage produces anoxia (lack of oxygen), which in turn causes more sick-ling and more damage.



In addition, patients experience occasional sickle cell crises—attacks of pain in the bones and stomach. Blood clots also may develop in the lungs, kidneys, brain, and other organs. A severe crisis or several acute crises can damage the organs of the body by impeding the flow of blood. This damage can lead to death from heart failure, kidney failure, or stroke. The frequency of these crises varies from patient to patient. A sickle cell crisis, however, occurs more often during infections and after an accident or an injury.

In 2004 the New England Journal of Medicine (Mark T. Gladwin et al, "Pulmonary Hypertension as a Risk Factor for Death in Patients with Sickle Cell Disease," vol. 350, no. 9, February 26, 2004) reported that researchers from the NIH and the Howard University Center for Sickle Cell Disease found that one-third of patients with SCD who had been screened with a noninvasive ultrasound method were found to have previously undetected moderate to severe pulmonary hypertension. This confirms earlier suggestions that pulmonary hypertension occurs in about 20%-40% of patients with SCD, which poses major health risks, including death. The researchers suggested that these findings were "so striking" that all patients with sickle cell should be regularly screened for hypertension and subsequently treated.


Both the sickle cell trait and the disease exist almost exclusively in people of African, American Indian, and Hispanic descent and in people from parts of Italy, Greece, the Middle East, and India. When one parent has the sickle cell gene, a couple's offspring will carry the trait but only if both the mother and the father have the trait can they produce a child with sickle cell anemia. According to the National Heart, Lung, and Blood Institute (NHLBI is an institute of the NIH;, SCD occurs in about seventy-two thousand Americans, most of whom are of African descent. The disease occurs in approximately one in five hundred African-American births and one in every one thousand to fourteen hundred Hispanic American births. Approximately two million Americans—including one in every twelve African-Americans—carry the sickle cell trait. Americans of African descent are advised to seek genetic counseling and testing for the trait before starting a family.

Testing is done by taking a sample of the amniotic fluid or tissue taken from the placenta as early as the first trimester of pregnancy. A genetic counselor evaluates the results and will be able to tell the parents what the chances are that their child will have the sickle cell trait or sickle cell anemia. Table 4.4 shows the average prevalence of SCD per one hundred thousand live births in the United States among different racial and ethnic groups.


In 1993 a federal panel of researchers, clinicians, and policy makers called for SCD screening of all newborns, because early diagnosis and treatment significantly improves future health. Because of intermarriage, it is becoming more difficult to be certain of a person's racial or ethnic background based on physical appearance, surname, or self-reporting. Many SCD sufferers could possibly be missed TABLE 4.4 Prevalence of sickle cell diseases by race or ethnic group, 1990 and unspecified years Richard S. Olney, "Table 2. Prevalence of Sickle Cell Disease (Hb SS, Sickle Cell-Hemoglobin C Disease and Sickle Beta-Thalassemia Syndromes) by Racial or Ethnic Group, per 100,000 Live Births, United States, 1990 and Unspecified Years," in "Newborn Screening for Sickle Cell Disease: Public Health Impact and Evaluation" Genetics and Public Health in the 21st Century, Centers for Disease Control and Prevention, (accessed December 29, 2005)by exclusively screening a target population such as African-Americans.

Race or ethnic group Average prevalence per 100,000 live births
Note: Sickle cell diseases include Hb SS, sickle cell-hemoglobin C disease, and sickle beta-thalassemia syndromes.
White   1.72
Black 289
Hispanic, total   5.28
Hispanic, eastern states  89.8
Hispanic, western states   3.14
Asian   7.61
Native American  36.2

By 1993, thirty-four states and jurisdictions had already instituted the universal screening of infants recommended by an earlier study group of the NIH in 1988. Another ten states had targeted screening aimed at groups traditionally considered at higher risk, and eight states and jurisdictions had no sickle cell screening program. The cost of universal screening has not been studied, but many researchers and policymakers feel that the investment would pay great dividends. A machine to run sickle cell tests could cost between $5,000 and $30,000; material to conduct a single test costs $1 to $3. The American Academy of Pediatrics, the American Nurses Association, the National Medical Association (an organization of African-American physicians), and the Sickle Cell Disease Association of America endorsed the new guidelines for universal screening.



There is no universal cure for SCD, but the symptoms can be treated. Crises accompanied by extreme pain are the most common problems and usually can be treated with pain relievers. Maintaining healthy eating and lifestyle and prompt treatment for any type of infection or injury are important. Special precautions are often necessary before any type of surgery; for major surgery some patients receive transfusions to boost their levels of hemoglobin (the oxygen-bearing, iron-containing protein in red blood cells). In early 1995 a medication that prevented the cells from clogging vessels and cutting off oxygen was approved. Blood transfusions also may be used to treat or prevent associated problems, such as anemia, spleen enlargement, and recurring stroke.

At the 1993 National Institutes of Health Consensus Conference, a federal panel of experts on SCD recommended that all infants diagnosed with the disease receive daily doses of penicillin to prevent infections. Parents are urged to make sure that these children receive the scheduled childhood immunizations and are vaccinated against influenza, pneumonia, and hepatitis B by age two years. In the mid-1980s, 20% of children with SCD died before their first birthday; by 1993, primarily because of preventive antibiotics, that proportion had dropped to less than 3%. Although there are neither uniform SCD reporting nor national reports of incidence or prevalence, public health professionals believe that antibiotic prophylaxis (preventive treatment) has further reduced SCD mortality (Sickle Cell Guideline Panel, Sickle Cell Disease: Screening, Diagnosis, Management and Counseling in Newborns and Infants, Clinical Practice Guideline No. 6, Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services, April 1993).


Today, many adults with SCD take hydroxyurea, an anticancer drug that causes the body to produce red blood cells that resist sickling. In 1995 a multicenter study showed that among adults with three or more painful crises per year, hydroxyurea lowered the median number of crises requiring hospitalization by 58%. In 2003 an extension of that study showed that patients on hydroxyurea not only have fewer crises but also have a significant survival advantage when compared with SCD patients who do not take the medication. Subjects treated with it overall showed 40% lower mortality than others (Martin H. Steinberg et al., "Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia: Risks and Benefits Up to 9 Years of Treatment," Journal of the American Medical Association, April 2, 2003).

A 1996 international study found that bone marrow transplants were successful in curing SCD in sixteen of twenty-two patients—72.7% of the patients in the five-year study. Bone marrow is where new blood cells are produced. All of the participants in the study were under age fourteen years, had advanced symptoms, and had siblings who were compatible bone marrow donors. Four of the patients (18%) rejected the donor marrow, and their SCD symptoms returned. Two of the patients (9%) died ("Bone Marrow Transplantation for Sickle Cell Disease: A Multicenter Collaborative Investigation," New England Journal of Medicine, August 8, 1996).

Because of the high risks of bone marrow transplants and the difficulties of matching donors, transplants are not appropriate for every patient. Further studies are needed to test the procedure with older patients and to reduce the proportion of tissue rejects. Blood harvested from umbilical cords and placentas has been found to be less likely to trigger rejection or graft-versus-host disease, in which the transplanted cells attack the cells of the bone marrow recipient, causing organ damage.

Tay-Sachs Disease

Tay-Sachs disease (sometimes referred to as TSD) is a fatal genetic disorder in children that causes the progressive destruction of the central nervous system. It is caused by the absence of an important enzyme called hexosaminidase A (hex-A). Without hex-A, a fatty substance called GM2 ganglioside builds up abnormally in the cells, particularly the brain's nerve cells. Eventually, these cells degenerate and die. This destructive process begins early in the development of a fetus, but the disease usually is not diagnosed until the baby is several months old. By the time a child with TSD is four or five years old, the nervous system is so badly damaged that the child dies.


A baby with TSD seems normal at birth and usually develops normally for about the first six months of life, but then development slows. The child begins to regress and loses skills one by one—the ability to crawl, to sit, to reach out, and to turn over. The victim gradually becomes blind, deaf, and unable to swallow. The muscles begin to atrophy, and paralysis sets in. Mental retardation occurs, and the child is unable to relate to the outside world. Death usually occurs between ages three and five. There is no cure or treatment for this disease.


TSD is transmitted from parent to child the same way eye or hair color is inherited. Both the mother and the father must be carriers of the TSD gene to give birth to a child with the disease.

People who carry the gene for TSD are entirely unaffected and usually are unaware that they have the potential to pass this disease to their offspring. When only one parent is a carrier, the couple will not have a child with TSD. When both parents carry the recessive TSD gene, they have a one in four chance in every pregnancy of having a child with the disease. They also have a 50% chance of bearing a child who is a carrier. Prenatal diagnosis early in pregnancy can predict if the unborn child has TSD. If the fetus has the disease, the couple may choose to terminate the pregnancy.


Some genetic diseases, such as TSD, occur most frequently in a specific population. Individuals of Eastern European (Ashkenazi) Jewish descent have the highest risk of being carriers of TSD. According to the National Tay-Sachs and Allied Diseases Association, approximately one in every twenty-seven Jews in the United States is a carrier of the TSD gene, and 85% of the children who are victims of this disease are Jewish. Italians also have a higher than average risk of being carriers. In the general population, the carrier rate is one in 250.

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over 3 years ago

this are the information on disease that can be inherited by offspring from parent