More than 24,000 children are born with hearing loss in the United States each year. Boys Town National Research Hospital is a national leader in the diagnosis and treatment of children with moderate to profound hearing loss.
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The Human Genome Project: Where Will it Take Us?
Although it was known for centuries that certain traits or diseases are passed on within families; an amazing number of the mysteries of heredity have been unraveled only in the last quarter of this century. We now examine the number and the structure of chromosomes under the microscope; identify carriers of some recessive disorders before they have affected children; diagnose some diseases by DNA testing before there are any symptoms; and even a few human gene products such as growth hormone and insulin are being produced in commercial laboratories. However, for all the progress that has been made, little or nothing can be done for most of the human suffering from genetic diseases. Almost 5,000 genetic traits or diseases have been described (not a small feat by itself), but the majority of responsible genes have not been identified.
Human Genome Research
All of the genes for a species is referred to as the genome of that species. Human genome research is an effort to identify and sequence or read the code of all the human genes. In the United States, Congress has appropriated funds to the Department of Energy and the National Institutes of Health for support of the Human Genome Project to study the human genome. It has been estimated that an average of approximately $200 million annually from the United States budget will be required to complete the project in about 15 years. The U.S. is not alone in this endeavor; scientists in many other countries are pursuing the same goal. The Human Genome Organization (HUGO) is an international organization which coordinates human genome research efforts around the world.
The medical care for a few genetic disorders has been affected by DNA research thus far. With this concerted effort to map the entire human genome, medical care for everyone will be revolutionized because we all have potentially harmful genes that put our offspring at risk or put us at risk for disease in the adult years. Prior to considering the potential far-reaching effects of this project, it may be helpful to review some basic concepts.
Basic Genetic Concepts
The human genome is made up of 23 chromosomes which are in a structure of the cells called the nucleus. The chromosomes are made up of strings of DNA and a gene is a portion of the DNA. There are hundreds to thousands of genes in each chromosome, and the same genetic information is contained in the DNA of each cell of a given individual. Genetic information is coded by four units of the DNA called bases; adenine (A), thymine (T), guanine (G) and cytosine (C).
A triplet of bases is called a codon. There are 64 possible codons. Three of the codons are stop codons; they signal the end of a gene. Each of the other 61 codons codes for an amino acid. There are 20 amino acids; this means that more than one codon can code for the same amino acid. This helps protect us from some of the detriments of mutation since a change in a codon may be such that the new codon still codes for the same amino acid. A chain of amino acids are arranged in the same order as the codons of the DNA string. The amino acid chain goes through processing (joining with another amino acid chain or dropping out part of the chain, and folding upon itself) to form a protein which can perform its specific function. Each protein has a specific vital function such as directing the duplication of cells which is necessary for growth and for the replacement of cells. Or, the protein may be essential for the differentiation of the cell i.e., making it a muscle cell instead of a bone cell. Many genes direct the production of their particular proteins only in certain cells or at certain times and otherwise are turned off.
Mapping and Sequencing Genes
Mapping a gene refers to the process of identifying the particular section of DNA on a specific chromosome where that gene is. Less than 2% of the 50,000 to 100,000 human genes have been mapped and far fewer have been sequenced. Sequencing refers to the process of identifying the order of bases in a segment of DNA. The entire human genome contains approximately three billion bases. It has been estimated that the information from sequencing the human genome would fill the equivalent of 14 sets of the Encyclopedia Britannica. The goal of the human genome project is definitely an ambitious one. Although it is not part of the Human Genome Project, identification of normal and abnormal gene products will follow and open the door for treatment of genetic conditions.
Medical Advances
Mapping of the genome will greatly enhance the diagnostic capabilities of physicians. Testing for the gene that causes a specific trait or disease will provide a more accurate diagnosis and will make it possible to diagnose conditions even before any or at least some of the symptoms can be detected. Pre-symptomatic diagnosis may open the door for the possibility of preventing the symptoms from occurring. A futuristic example of this might be the identification of individuals with a gene for adult onset hearing loss before any hearing is lost, and then providing the normal gene product so that they do not lose any hearing. Another example may be identifying the hearing impaired children who have Usher syndrome before they have any changes in their retinas and transplanting the Usher genes in the retina with normal genes so that they do not develop retinitis pigmentosa. These types of treatment advances may not be possible for all genetic disorders, but increased understanding of the genetic basis will bring us closer to effective management of many disorders.
Risk Identification
Many of the more common adult health problems such as heart disease and cancer are thought to have a genetic component that adds to the risk of environmental exposures. If the genetic components could be identified, it would be possible to screen for those with a high genetic risk. Those with an increased genetic risk could be taught how to control their environmental exposures. Perhaps eventually we would be able to alter the genetic risk also.
Presymptomatic Testing
The capability for DNA presymptomatic or predictive testing will not be followed immediately by the ability to treat or prevent the symptoms. However, improved diagnostic ability by itself can provide the individual and family with important information. The genetic diagnosis would make it possible to identify the inheritance pattern for a condition in a family where it has been previously unclear. This would then provide accurate information about who has a risk of recurrence in their offspring and how high or low that risk actually is. It also may provide important information for preventive measures which may be imperfect but better than nothing. An example of this would be: a young woman identified as having the gene for hereditary breast cancer may benefit from annual mammograms; her sister who does not have the gene could avoid the radiation exposure of annual mammograms during her young adult years.
This new diagnostic or presymptomatic testing would not be without some significant dangers. The lag between testing capability and treatment capability can mean years of anxious waiting or even greater harm for some who are tested. It has been possible for the last few years to presymptomatically identify the gene carriers of Huntington Disease within affected families.
Huntington Disease is a neurodegenerative disease with onset being typically in the middle adult years and usually resulting in a type of senility and progressive physical disability followed by early death. It is autosomal dominant so the child of an affected individual has a 50% chance of being affected also. Currently there is no means of interfering with the course of the illness. Therefore, those who are identified as gene carriers have no hope of avoiding this dread disease whose effects they know all too well after watching their affected family members live and die with it. Some family members have availed themselves of the predictive testing so that they can plan for the future or just to end the agonizing wait to find out if they have the gene. Most who are at risk for Huntington Disease have not chosen to have predictive testing at this time. Family members and health care providers have had significant fears of psychological harm, perhaps even suicide, due to the information obtained through predictive testing. Therefore, the testing is available only to those who have been willing to participate in hours of psychological testing and counseling as well as extensive genetic counseling. There has been much debate about the potential for good and for harm to at risk individuals, their families and the relationships within those families as a result of predictive testing prior to finding a treatment.
Predictive testing for Huntington Disease provides a very dramatic example of the potential for good and for harm; the genome project will make it possible for other equally devastating disorders to be diagnosed presymptomatically long before there are effective therapies. Currently there are only a few centers around the country that have the necessary personnel in place to provide the evaluation and counseling that must be a part of predictive testing. As the potential to predict other diseases becomes a reality, there will be pressure to eliminate some of these safeguards because of a lack of necessary personnel resources.
Concerns about predictive testing also extend to issues surrounding insurance coverage. Will insurance companies require testing for genetic liabilities prior to providing coverage, or will they insist on their right to review the results of any test they pay for? Once the liability is known, the insurance company will have to charge a higher premium or deny coverage. If they don't, their competitiors will and eventually the original company will have too many clients with high liability to stay in business. As noted earlier, we all carry genetic liabilities which could make us ineligible for insurance.
Gene Therapy
One of the major purposes for the Human Genome Project is to find effective treatments for the prevention of genetic disorders. Because many genes have already caused their harm long before birth, it may be necessary to replace those genes in the ovum or sperm in order to prevent the harm. This would mean the replacement gene would be passed on to the next generation. On the surface this seems to be very beneficial, but many have concerns about some deeper issues. We know that two copies of the gene for sickle cell trait cause sickle cell disease. We also know that a single copy of the gene provides protection from malaria. This protection is important in tropical countries where malaria is prevalent. If we tried to replace normal genes for sickle genes in germ cells, we would also eliminate that protection from malaria. There may be beneficial features to many other genes that are harmful in double copies; it is important that we do not eliminate genes that are helpful. Aside from the potential interference with a natural selective advantage, many have concerns about interfering with God's design, obtaining informed consent from the future generations that will be affected by germline manipulation, parental expections for the perfect child, building a master race, etc.
Another way of treating genetic disease may be to replace the faulty gene with a normal gene only in the tissue that is affected by the faulty gene or by supplying the normal gene product that is missing. For most, this type of gene therapy does not carry the same ethical concerns or concerns for unknown harms. However, for many deaf individuals, even this type of therapy would be seen as an attack on their culture.
There are many other social, legal and ethical issues surrounding the genome project. Some of these include DNA testing for purposes of identification by the armed services or the judicial system; employer use of DNA testing to identify those at high risk of disease from job-related exposures; increased understanding of genetic influences on human behavior, etc. All of these issues have the potential for good as well as harm. Approximately 3% of the Human Genome Project budget has been allocated for the study of these issues and for education of the general public as well as health care providers. It is up to all of us to become informed and to express our thoughts and concerns through public forums and communications with our elected officials.
Glossary
Carrier:
a person who has one recessive gene and one dominant gene in a particular pair is said to be a carrier of the recessive gene. Except through DNA testing, carriers usually not identified until they have a child with the recessive trait.
Chromosome:
a string of DNA which carries hundreds to thousands of genes. There are 23 pairs of human chromosomes.
Codon:
a triplet of DNA bases that codes for a specific amino acid or provides a stop message at the end of a gene.
DNA:
the abbreviation for deoxyribonucleic acid, within which the genetic code exists. It is arranged in a helical pattern.
Dominant:
a gene that is expressed even when it is paired with a different gene.
Gene:
a section of DNA with the coded instruction for the production of a protein that is essential to one aspect of the growth, development or continued functioning of an organism.
Gene product:
the protein that is produced from the code of a specific gene, i.e.. growth hormone is the gene product of the human growth hormone gene.
Genome:
the total genetic make-up of a specific organism.
Recessive:
a gene that is expressed only when paired with another recessive gene or when it is the only copy of that gene.
Retina:
the back part of the inside of the eye; it is the portion of the eye that receives the image that is being seen similar to the lens of a camera.
Retinitis Pigmentosa:
a condition of the retina in which pigment accumulates on the retina thus interfering with vision. At first the individual has problems with night vision and then peripheral vision; eventually all they have is a small degree of central vision and for some that is lost also.
Sickle cell disease:
an autosomal recessive disorder of the hemoglobin that causes red blood cells to take on a "C" or sickle shape instead of the usual spherical shape of normal red blood cells. The sickle cells do not carry oxygen as efficiently as normal and their shape causes them to bunch up in the blood vessels reducing blood flow beyond the clog.
Usher Syndrome:
a recessive disorder that includes congenital hearing loss and later development of retinitis pigmentosa.
By Susan T. Tinley
Susan has an R.N. and a M.S. and is a Genetics Nurse Clinician at the Hereditary Cancer Prevention Clinic at Creighton University.
Date Originally Created: Fall of 1993
The information presented here first appeared in publications of the Boys Town National Research Register for Hereditary Hearing Loss, the National Institute on Deafness and Other Communication Disorders (NIDCD), Hereditary Hearing Impairment Resource Registry (HHIRR), or the Boys Town Research Registry for Hereditary Hearing Loss.
The Boys Town Research Registry for Hereditary Hearing Loss
The Boys Town Research Registry for Hereditary Hearing Loss (Registry) is designed to foster a partnership between families, clinicians and researchers in the area of hereditary hearing loss/deafness through three primary functions. First, the Registry disseminates information to professionals and families about clinical and research issues related to hereditary deafness/hearing loss. Second, the Registry collects information from individuals interested in supporting and participating in research projects. This information is used to support the third function of the Registry - matching families with collaborating research projects.
For more information, contact us at:
Research Registry for Hereditary Hearing Loss
555 N. 30th Street Omaha, NE 68131
800 320-1171 (V/TDD)
402 498-6331 (FAX)