Genetics: Changing Health Care in the 21st Century

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Genetics: Changing Health Care in the 21st Century Shirley L. Jones, RNC, MS

Advances in human genetics are rapidly changing the scope of information and care that can be provided to health care consumers. By the year 2005 it is expected that the entire human genome will be mapped and all 70,000-100,000 genes will be identified. Currently, there are more than 5,000 known single-genedisorders. With the movement of specialized health services into the primary care setting, nurses increasingly will need to be knowledgeable about genetic disorders, screening/diagnostic tests, and implications for health care. In addition, the management of genetic information raises issues of informed consent, privacy and confidentiality,truth telling and disclosure, and nondiscrimination. JOGNN,25,777-783; 1996.

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dvances in human genetics will change the concept and delivery of health care in the 21st century. From a historical perspective, human genetics as a clinical specialty did not come into its own until the mid20th century. However, the scientific principles that form the foundation of this discipline were proposed by Gregor Mendel in the mid-1800s. His work eventually led to an understanding of the basic patterns of inheritance for single-gene disorders and became known as Mendelian patterns of inheritance for single-gene disorders (that is, autosomal recessive, autosomal dominant, sex-linked recessive, and sex-linked dominant). Medical science during the 100 years between the mid-19th and mid-20th centuries was concerned with the curtailment of infectious diseases and the development of surgical therapies. Work in the area of human genetics was centered around investigating possible causes of diseases that appeared to be unusually common within a family (McKusick, 1993). The ability to identify the correct number of chromosomes in a human cell as 46, which happened in 1956, was a critical advance for the field of cytogenetics (the study of the structure and function of the cell, especially the chromosome). Initially, size determined which

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group (A-G) a chromosome was placed into during the analysis of a blood or tissue sample. The test results, presented in the form of a karyotype, are a photograph of the chromosomes within a single cell chosen from among the many cells that are found on a laboratory slide prepared from the specimen. This allowed medical science to identify if there were more or less than 46 individual chromosomes in each cell. For example, in 1959, the genetic basis for Down syndrome (trisomy 21) was found to be one additional chromosome in the G group. For the most part, scientists early on were limited to determining if an entire chromosome was missing or extra (Thompson, McInnes, &Willard, 1991). Variations in the staining preparation process, developed during the 1960s to make the chromosomes visible through the lens of the microscope, were found to identify a unique pattern of banding for each of the 23 pairs of chromosomes (Thompson et al., 1991). The development and refinement of staining methods assisted cytogeneticists in delineating deletions and duplications of genetic material within any single chromosome. Cri du Chat syndrome was the first disorder found to have a genetic cause as a result of a deletion of a portion of one chromosome (short arm of chromosome 5 ) . Many genes usually are affected by a structural change in the chromosome. It is important to note that the clinical findings associated with structural changes are the result of either too little or too much normal genetic material. The identification of the double helix structure of deoxyribonucleic acid (DNA) by Watson and Crick made possible the ability to delineate alterations in a single gene located within a chromosome. However, a single gene can not be seen through the lens of a microscope. Laboratory methods to study the single gene had to be developed. Electrophoresis was used to detect hemoglobinopathies such as sickle cell disease or thalassemia, but its application initially was limited. The field of molecular genetics came into being with the discovery of restriction fragment length polymorphisms (RFLPs) by Botstein, White, Skolnick, and Davis in 1980. When DNA

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is exDosed to restriction endonucleases, it cuts into pieces. The specific size of each DNA fragment is an inherited characteristic dependent on DNA sequence. Variations in DNA seauence (RFLP) are inherited in families in a Mendelian fashion. The variability of the length of the DNA fragment provides scientists with the ability to follow certain traits within families (Antonarakis, 1989; Thompson et al., 1991).

The Human Genome Genetic maps represent an accumulation of knowledge about the various genetic markers (detectable DNA sequences) identified through laboratory procedures such as RFLP analysis. The importance of genetic markers and genetic maps is the information they provide about the association between two markers seen on the same chromosome that are in close physical proximity to each other. These markers may be used to analyze the blood of families with a known genetic disease and help to determine the region within a chromosome in which the gene responsible for the disorder is located. Subsequently, researchers attempt to sequence (a physical map) the gene. (For an in-depth discussion of genetic markers and gene maps, the reader is referred to the article by Lessick and Williams, 1994). It is estimated that 70,000-100,000 genes comprise the human genome, the blueprint for the growth and development of each unique individual. Scientists recognized that if a national effort was not launched, the task of identifying all of the genes in the human genome would remain a daunting task, given that by 1988 only 2,000 genes had been identified. The idea to develop a national consortium began in the Department of Energy (DOE). Because many of the outcomes of the research effort would affect health and health care, the National Institutes of Health (NIH) participated in the dialogue to establish goals for a national initiative. The Human Genome Project (overseen jointly by the NIH and DOE) was approved by Congress in 1987 and received funding beginning in 1988 (Blatt, 1992). The o5cial start of the 15year project was 1990. The NIH established the National Center for Human Genome Research (NCHGR). The goals of NCHGR are:

It is estimated that 70,000-100,000 genes comprise the human genome, the blueprint for the growth and development of each unique individual.

ognition was given to the importance of proactively addressing the ethical, legal, and social issues associated with new knowledge and technology. Historically, the application and implementation of research findings has preceded discussion or resolution of such issues. This project is attempting to simultaneously explore these questions and the discovery of the new knowledge. Since the inception of the Human Genome Project, almost 4,000 additional genes have been identified, bringing the total to more than 6,000 (E. Thomson, personal communication, September 26, 1995). Society’s concept of wellness and illness is being redefined as research delineates between genetic difference (normal variants) and genetic disease (altered health status). As work in human genetics continues, and recognizing that more than 5,000 single-gene disorders have been delineated, nurses will need to identify and integrate new knowledge and skills into professional practice.

Genetic Evaluation, Diagnosis, and Counseling

Goal 7 is unique to the Human Genome Project. For the first time in the advancement of human science, rec-

Clinical findings and family history are the tools of the geneticist and, before advances in laboratory genetics, comprised the genetic evaluation. A careful examination of the individual believed to have a genetic disorder is conducted. The family history is reviewed to learn if other individuals in that kinship have similar physical or mental characteristics. In some cases it is possible to delineate which genetic disorder is expressed in the proband, the first person who brought the family to the attention of the geneticist. Down syndrome is an example of a disorder in which the physical and mental findings have been well established and do not resemble any other genetic disorder. However, until the development of cytogenetic laboratory methods, counseling about reproductive risk for trisomy 21 caused by various genetic alterations such as nondisjunction or a parental translocation of chromosome 21, could not be differentiated. Each type of anomaly carries a different risk for occurrence and recurrence. Figures 1-3 are examples of human karyotypes. Figure 1depicts the karyotype of a normal female. Figure 2 depicts the karyotype of a male with a translocation of genetic material from chromosome 13 to chromosome 10. Figure 3 is a schematic representation of this translocation, and illustrates the subtlety of such rearrangements. Biochemical analysis of the blood or other tissue for an enzyme known to be the product of normal gene function or identification of abnormal levels of certain pro-

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1 . to map the entire human genome; 2. to sequence the order of the human genome; 3. to map and sequence the genomes of model organisms; 4. to develop computer informatics; 5 . to support research training programs; 6 . to develop innovative technologies and facilitate technology transfer; and 7.to develop programs and policies that address the ethical, legal, and social implications of the outcomes associated with the activities of the Human Genome Project (Blatt, 1992).

Celebrating the Future

productive risks, leaving couples to make reproductive decisions with limited information. Fragile X is an example of a disorder for which family history alone often can identify the reproductive risk. If a male child is born with Fragile X, the mother of that child is an obligate carrier of the altered gene. In a future pregnancy, the mother has a 50% chance of having sons with the disorder. Daughters also have a 50%chance of receiv-

Figure 1. Normulj&ude kuyo(vpe. Courle
teins additionally assisted the clinical geneticist in diagnosing genetic disorders or identifying individuals who carried an altered gene but were not affected. Newborn screening programs are an early example of the use of biochemical analysis to identify infants with a metabolic disorder, such as phenylketonuria, maple syrup urine disease, or galactosemia. Testing for carrier status (an individual has one altered gene and one normal gene, and the disorder requires two altered genes to be expressed) of other disorders was highly successful if the individual had a high or low level of the enzyme. Early Tay Sachs screening measured the level of hexosaminidase A to identify carriers of the gene for Tay Sachs. Unfortunately, a gray zone existed between the low normal and carrier range for hexosaminidase A activity, which made it difficult to determine the carrier status of some individuals. Preconception reproductive risk counseling was particularly difficult if one member of the couple was a known carrier of the gene and the other individual had an inconclusive result. Tay Sachs screening now can be done by molecular analysis, and carrier status can be definitively determined. Other genetic disorders did not lend themselves to cytogenetic or biochemical analysis. Geneticists began to subcategorize certain disorders according to clinical findings and family history to provide information about prognosis and reproductive risk. Osteogenesis imperfecta (01) is such a disorder. In the case of 01, prognosis ranged from an occasional fractured bone to lethal in utero fractures (Byers, 1989). The reproductive risk for the parents to have a second child with the disorder could be virtually zero (a spontaneous new mutation of the gene occurred in the child), or 25% (both parents carry the altered gene and two altered genes are required for expression in the child), or 50% (one parent carries the altered gene and only one gene is required for expression). Without molecular genetic testing it was impossible to avoid the possibility of misdiagnosis. Thus, genetic counseling included an explanation of the range of re-

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ing the altered gene; however, only 60-70% of females with the altered gene will have clinical findings (Rousseau et al., 1991). With another sex-linked disorder, hemophilia, a negative family history (no other individual with the disorder) before the birth of a son with the disease must be interpreted with caution. Absence of another family member with the disorder may represent the occurrence of a spontaneous new mutation in the son (and thus no increased reproductive risk for either the parents or siblings) or a uniformative family history (members of the kindred are either predominantly female or all males received the normal gene) with the real possibility of a 50% recurrence risk. Previously, if the sister of a male with hemophilia wished to know her carrier status, this could not be determined without linkage analysis (use of genetic markers to follow the trait in the family). All too frequently the genetic markers within a family were not informative, and the answer could not be provided. This situation also was true for cystic fibrosis (CF) before isolation of the gene. Identification of the gene alteration that results in a genetic disorder provides the capability to test specifically for a gene and to determine whether an individual does not have the gene, has only one copy, or has two copies of the gene. Unfortunately, although the test is definitive for disorders such Tay Sachs and Huntington disease, it is not definitive for some other disorders. The gene for CF was found to be located on the long arm of chromosome 7. After that initial finding (Rommens et al., 19891, it has been learned that there are more than 300 known alterations in the gene for CF, although 14 mutations account for 87-95% of carrier status. This has hin-

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Figure 2. Mule kuyotvpe with trunslocution [46.XY.t(10:13)(q26:432). Cowleu?,of!? Howard-Peebles.Genelics& IVF Instilute. Fuifm. Virginia

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Figure 3. Schematic of translocation depicted in Figure 2. Courtesy qfP. Howard-Peehles. Genetics G IVF Institute. Faifm. Virginia.

dered the ability to offer broad population screening even though the risk for being a carrier of CF is 1:25.

Carrier, Predisposition, and Presymptomatic Screening

laboratory testing have created new categories of individuals requesting genetic evaluation. The first and traditional example are individuals who wish to know if they carry an altered gene for an autosoma1 recessive or sex-linked recessive disorder. Unlike autosomal dominant disorders, in which a single copy of the gene will result in expression of the disorder, autosoma1 recessive disorders require two copies of the altered gene. This also is true for females at risk for sex-linked recessive disorders. Males do not have a second X chromosome to balance the effects of an altered gene on their only X chromosome and thus require only one copy of the altered gene to express the disorder. If an individual carries an autosomal recessive gene, he or she appears healthy and usually has no clinical findings associated with the disorder. However, such individuals do have a reproductive risk. They have a 50% chance that they will pass on their carrier status to their child. If their reproductive partner also carries the same altered gene, there is a 50% chance the child will be a carrier like the parents, a 25% chance the child will not receive an altered gene, and a 2 5 % chance that the child will have the disorder because of the inheritance of abnormal genes from both parents. It has long been recognized that certain cancers, hypertension, and diabetes appear to recur within families. As the gene for a specific adult onset disorder becomes identified, more individuals will use genetic services to determine their risk. This is the second category of healthy individuals seeking genetic evaluation. This form of screening is known as predisposition testing. That is, the individual found to have the gene that causes a specific genetic disorder is said to be predisposed to a particular disease. There is some level of risk that the individual may have the disease within his or her life; however, environmental issues and appropriate health promotion activities may reduce that risk.

The provision of genetic services includes genetic counseling. This is a process in which information about a genetic disorder is shared with an individual, couple, or family. Genetic counseling may be initiated before evaluation and diagnosis of an individual as part of the informed consent process, or it may be an outgrowth of a diagnosis based on clinical and laboratory findings. Multiple sessions to assist in the understanding and assimilation of the information may be required. Nurses have been involved primarily in the identification, referral, and follow-up of individuals, couples, and families who receive tertiary level genetic services. This role is changing with advancements in genetic technology, evaluation, and diagnosis. Genetic services are moving into the primary care setting, and health care providers will be expected to be knowledgeable about genetic disorders, screening/diagnostic tests, implications for health care, and reproductive risk. Maternal serum alpha fetoprotein (MSAFP) screening is the most recent example of such a model. MSAFP screening was found to be successful in identifying neural tube defects in the fetus. With the addition of estriol and Beta human chorionic gonadotrophin levels to the screen, a risk for the presence of a chromosomal anomaly in the fetus has been added to the information provided. Appropriate counseling by the primary health care provider before collection of a blood specimen eliminates the need for all pregnant women to seek tertiary level genetic services. A referral for specialized genetic services is initiated if an abnormal level is identified or specifically desired by the woman. Genetic evaluation (clinical, laboratory, or both) previously focused on the individual believed to have clinical findings of a genetic disorder. Diagnosis of the proband usually was the impetus to seek genetic services. Genetic services also are sought by those who believe they may be at risk for a genetic disorder but are otherwise healthy at the time of consultation. The advances in

An example of predisposition testing is screening for the breast cancer gene (BRCAI), which was identified on the long arm of chromosome 17 (Hall et al., 1990). This gene is a tumor suppressor gene (Miki et al., 1994). If the gene is not functional, tumor growth may ensue during the lifetime of the individual. It has been found that the lifetime risk for breast cancer if the individual has an altered BRCAl gene is 80-85%, and there also is an increased risk for ovarian cancer (King, Rowell, & Love, 1993; Weber, 1996). Men may carry an altered BRCAl gene and are at increased risk for prostate and colon cancer. Both men and women can transmit the altered BRCAl gene to either their sons or daughters. Like CF, it

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Certain cancers, hypertension, and diabetes have a genetic basis.

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appears that the BRCAl gene has multiple mutations, many of which are unique for a given family. Most of the screening for BRCAl has been conducted among families with a high incidence of breast or ovarian cancer. Evidence suggests that the inherited forms of breast cancer account for approximately 5-10% of all breast cancers (Szabo & King, 1995). In October 1995, Struewing et al. announced that the frequency of a particular breast cancer mutation (BRCAl 185delAG) among Ashkenazi Jewish individuals is 1%. This finding has raised the question of whether screening among Ashkenazi Jewish families should be made widely available. The issues being debated are the implications of testing outcomes and informed choice. Historically, the informed consent process includes information about the disorder, the screening/diagnostic test, the limitations of the testing, and what options are available once results are known. It is the last two components of informed consent that have caused concern. There is no consensus on the best prevention strategy for individuals with an altered BRCAl gene (Weber, 1996). Among proponents of not offering the test outside of research protocols, there also is a question with regard to the prognosis for individuals identified with the gene who have no symptoms. That is, does having the altered gene and no clinical findings equal being at an 85% lifetime risk for the development of breast cancer? Without this information, it is thought that general population screening for breast cancer should not be offered. Others believe that identification of an altered gene in an individual with no symptoms does significantly increase the lifetime risk of breast cancer. These individuals propose that if the individual is informed of the lack of consensus among health care providers and the inherent benefits and limitations of each treatment option, it is the right of the individual, in consultation with his or her health care provider, to choose whether or not to have testing. Individuals seeking presymptomatic testing comprise the third category of healthy consumers seeking genetic services. The individual who seeks presymptomatic testing is at a high risk of having an adult onset disorder solely based on inheritance of an altered gene. Reasons given for pursuing such testing have ranged from concern about reproductive risk to life decisions (such as education, employment, marriage) to mental health. Huntington disease is the classic example. It is a progressive neuropsychiatric disorder that usually develops between 35 and 50 years of age. It is a disorder that follows the inheritance pattern of a dominant single-gene disorder (each child has a 50% chance of having inherited the altered gene and, if inherited, a 100% risk of the disorder). The use of predictive testing by at-risk individuals has been limited (Crauford, Dodge, Kerzin-Stowar, & Harris, 1989). Fear of knowing one has the altered gene and fear of not having the altered gene are issues in presymptomatic testing. Survivor guilt often is felt by an individual who does not have the altered gene when multiple members of the family do. Regardless of whether testing is sought, there remains a strong desire

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to eliminate reproductive risk. Prenatal diagnosis, either chorionic villus sampling or amniocentesis, is a reproductive option. However, if an affected fetus were identified, the genetic status of the at-risk parent would be known. Individuals who do not wish to know whether or not they have the gene are left with the decision to not have a biologic child or to accept the 50% risk and have a biologic child. Schulman, Black, Handyside, and Nance (1996) have proposed a reproductive alternative for individuals who are at risk for a dominant disorder, such as Huntington disease, but who d o not desire presymptomatic testing. Preimplantation genetic testing (PGT) of the human embryo created through in vitro fertilization (IVF) was first reported by Handyside, Kontogianni, Hardy, and Winston in 1990. The purpose of the testing is to d o genetic analysis on one or two cells removed from the embryo before cellular differentiation occurs. The outcome of the testing process is shared with the couple, who make the decision as to which embryos will be transferred to the mother after all information is discussed. Schulman et al. (1996) have suggested that, with informed consent, couples at risk for a disorder such as Huntington disease may elect to have PGT, but request that all information about the number of oocytes retrieved during the IVF process, the number of embryos formed, and the outcome of the genetic analysis not be shared with them. They will simply be informed of the number of embryos without the altered gene that are available for transfer or possible cryopreservation. This protocol would eliminate the need to learn the genetic status of the at-risk individual, while eliminating this specific genetic risk for the child conceived by this process.

Reproductive Options Individuals or couples at risk for transmitting any genetic disorder to a biologic child will seek to reduce or eliminate this possibility. Amniocentesis is reported to have a 0.5-1% risk of pregnancy loss, whereas chorionic villus sampling (CVS) has been found to have a 1-2% risk. Amniocentesis typically is performed between the 15th and 16th week of pregnancy. Testing with this method of fluid extraction also may be done as early as 12-14 weeks of gestation. CVS usually is performed between the 10th and 1lth week of pregnancy. The villi or fluid obtained through these procedures is analyzed for evidence of the genetic disorder. As cytogenetic and molecular genetic technology has increased, so have the numbers of disorders amenable to prenatal diagnosis. In addition, high resolution ultrasound has provided the ability to assess the fetus for structural anomalies using a noninvasive technology, as opposed to fetoscopy, which is associated with a significant risk of pregnancy loss. As noted, PGT is another reproductive option available. Individuals/couples may elect this method when amniocentesis or CVS are not considered reasonable alternatives. The use of donor gametes is a third reproductive av-

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enue that can be pursued. The advantages of this alternative in comparison to traditional postnatal adoption is that half of the genetic contribution to the child is from one of the parents, and the couple has the opportunity to experience pregnancy and the birth process. Programs that provide donor gametes have an ethical and legal obligation to carefully screen potential donors for medical, genetic, and psychologic risk. Until recently, the medical records of the donors and the records of which individual used which donor were not maintained for more than 5 years. Advances in genetic technology have raised the issue of communication of new information learned about a donor or the genetic child of a donor years after the gamete donation has occurred. National registries have been suggested as a method of transmitting important health information without breaching the confidentiality of an anonymous gamete donation. In the absence of a national registry, it is the responsibility of each individual program to establish institutional policy regarding how such information will be managed and that the policy be shared with potential donors and recipients.

tained within the booklet are issues such as informed consent versus implied consent, privacy and confidentiality, truth telling and disclosure, and nondiscrimination. For example, nurses historically have participated in the delivery of care based on implied consent. In one instance, this is evident when an individual seeks care because of symptoms of anemia. A detailed explanation of the reason to do the testing, the possible outcomes of the testing, and any risks associated with the testing procedure to obtain a blood specimen for hemoglobin and hematocrit levels are not reviewed with the individual, and a written informed consent document is not required. This lack of information sharing and documentation of informed consent is not appropriate for genetic testing; it is incumbent upon the nurse to safeguard the process of informed choice and written informed consent before genetic evaluation and testing.

Managing genetic information is a nursing responsibility.

Implicationsfor Nursing Practice The nurse as the omnipresent health care provider has a responsibility to be knowledgeable about the availability, benefits, and limitations of genetic evaluation, diagnosis, and counseling. In addition, many of the genetic services currently provided at the tertiary level will be offered in the primary care setting in the near future with the movement of health care services out of the hospital. Genetic technology will continue to advance, thus making it imperative that the nursing community address the impact of this clinical science on professional practice. To identify current nursing practice in relation to advances in genetic technology, the American Nurses Association (ANA)applied for and received funding from the NIH through the Human Genome Project. The purpose of the grant was to “gather and analyze information about the ways in which nurses are involved in eliciting, transferring and using genetic information in their work with clients and families, to identify ethical dilemmas that nurses face in their various roles, and to develop resources to assist nurses in managing the professional and ethical challenges related to genetic advances” (Scanlon & Fibison, 1995, p. 3). To achieve this goal, the ANA conducted a telephone survey of 1,000 nurses. Lack of confidence to perform nursing interventions associated with the delivery of genetic services and lack of competence in genetics knowledge were found to be the major themes (C. Scanlon, personal communication, September 26,1995). The publication Managing Genetic Information: Implications for Nursing Practice was developed by the project team to disseminate the findings of the survey, present guidelines for nursing practice, and identify recommendations for practice, education, research, and policy (Scanlon & Fibison, 1995). Key to the discussion con-

It has been suggested that all disease has a genetic basis (F. Collins, personal communication, September 26, 1995). It is highly probable that the Human Genome Project and the associated advances in genetic technology that will be the outcome of the program will support this statement, thus changing the practice of health care delivery as the new millennium begins. Nursing interventions that incorporate education and counseling, cli-

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Similarly, the ANA Codefor Nurses with Interpretive Statements (1985) warrants that nurses shall maintain an individual’s privacy; hold in confidence all information shared or learned in the act of providing care; be truthful and provide correct and accurate information; and ensure that care is delivered without discrimination. The preponderance of genetic information (such as family history, simple laboratory tests for blood type or cholesterol concentration, or findings from a physical examination) contained within the medical record alone makes the task intimidating. How can nursing fulfill the responsibility of the profession? First, nurses should become aware of characteristics of genetic information and where it may be found. Second, nurses must increase their competence and confidence in their knowledge of genetics and related practice skills. Third, nurses need to participate in dialogue with other health care providers and consumers as policy is developed for the dissemination and use of genetic technology. Finally, areas for nursing research need to be identified and investigated.

Conclusion

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e n t advocacy and a u t o n o m y , and anticipatory g u i d a n c e can no l o n g e r be p e r f o r m e d without k n o w l e d g e of clinical genetics. Currently, m o s t n u r s e s have n o t integrated into practice t h e k n o w l e d g e and skills that are r e q u i r e d for g e n e t i c service delivery within t h e primary care health setting. The profession m u s t c o n t i n u e t o e d u c a t e all nurses, d e v e l o p m e t h o d s t o effectively disseminate new information i n a timely m a n n e r , and assist i n t h e assimilation of t h e k n o w l e d g e and skills requisite t o t h e provision of quality n u r s i n g care.

References American Nurses Association. (1985). Codefor Nurses with Interpretive Statements. Kansas City, Missouri: Author. Antonarakis, S. ,E. (1989). Diagnosis of genetic disorders at the DNA level. The New England Journal of Medicine, 320, 153-163. Blatt, R. J. R. (1992). What is the human genome project? The Genetic Resources, 6, 5-18. Botstein, D., White, R. L., Skolnick, M., & Davis, R. W. (1980). Construction of genetic linkage map using restriction fragment length polymorphisms. AmericanJournal ofHuman Genetics, 32, 314-331. Byers, P. H. (1989). Inherited disorders of collagen gene structure and expression. American Journal of Medical Genetics, 34, 72-80. Crauford, D., Dodge, A,, Kerzin-Stowar, L., & Harris, R. (1989). Uptake of presymptomatic predictive testing for Huntington's disease. Lancet, 2, 603-605. Handyside, A. J., Kontogianni, E. H., Hardy, K., &Winston, R. M. (1990). Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplications. Nature, 344, 768-770. Hall, J. M., Lee, M. K., Newman, B., Morrow, J. E., Anderson, L. A., Huey, B., 81 King, M-C. (1990). Linkage of early onset familial breast cancer to chromosome 17q21. Science, 250, 1684- 1689. King, M-C., Rowell, S., C(r Love, S. M. (1993). Inherited breast and ovarian cancer: What are the risks? What are the choices? Journal of the American Medical Association, 269,1975-1980. Lessick, M., &Williams, J. (1994). The human genome project: Implications for nursing. MEDSURG Nursing, 3, 49-58. McKusick, V. A. (1993). Medical genetics: A 40-year perspective on the evolution of a medical specialty from a basic science. Journal of the American Medical Association, 270, 235 1-2356. Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P. A., Harshman, K., Tavtigian, S., Liu, Q., Cochran, C., Bennett, L. M., Ding, W., Bell, R., Rosenthal, J., Hussey, C., Tran, T., Mc-

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Clure, M., Frye, C., Hattier, T., Phelps, R., Haugen-Strano, A., Katcher, H., Yakumo, K., Gholami, A., Shafer, D., Stone, S., Bayer, S., Wray, C., Bogden, R., Dayanath, P., Ward, J., Tonin, P., Narod, S., Bristow, P. K., Norris, F. J., Helvering, L., Morrison, P., Rosteck, P., Lai, M., Barrett, J. C., Lewis, C., Neuhausen, S., Cannon-Albright, L., Goldgar, D., Wiseman, R., Kamb, A., & Skolnick, M. H:(1994). A strong candidate for the breast and ovarian cancer susceptibility gene BRCAl. Science, 26666-71. Rommens, J. M., Iannuzzi, M. C., Kerem, B-S., Drumm, M. L., Melmer, G., Dean, M., Rozmahel, R., Cole, J. L., Kennedy, D., Hidaka, N., Zsiga, M.,Buchwald, M.,Riordan, J. R., Tsui, L-C. & Collins, F. S. (1989). Identification the cystic fibrosis gene: Chromosome walking and jumping. Science, 245, 1059-1065. Rousseau, F., Heitz, D., Biancalana, V., Blumenfeld, S., Kretz, C., Boue, J., Tommerue, N., van der Hagen, C., DelozierBlanchet, C., Croquette, M. F., Gilgenkrantz, S., Jalbert, P., Voelckel, M. S., Oberle, I., & Mandel, J. L. (1991). Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. The New EnglandJournal ofMedicine, 325,1673-1681. Scanlon, C. (1995). Personal communication. Director, Center for Bioethics, American Nurses Association. Scanlon, C., & Fibison, W. (1995). Managinggenetic information: Implications for nursing practice. Washington, DC: American Nurses Association. Schulman, J. D., Black, S. H., Handyside, A., & Nance, W. E. (1996). Preimplantation genetic testing for Huntington disease and certain other dominantly inherited disorders. Clinical Genetics, 49,57-58. Struewing, J. P., Abeliovich, D., Peretz, T., Avishai, N., Kaback, M. M., Collins, F. S., & Brody, L. C. (1995). The carrier frequency of the BRCAl 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nature Genetics, 11, 198-200. Szabo, C. I., & King, M. C. (1995). Inherited breast and ovarian cancer. Human Molecular Genetics, 4, 1811-1817. Thompson, M. W., McInnes, R. R., & Willard, H. F. (1991). Thompson G- Thompson genetics in medicine. Philadelphia: W. B. Saunders. Weber, B. (1996). Genetic testing for breast cancer. Scient$c American, 274, 12-21.

Addressfor correspondence:Shtrley L. Jones, RNC, MS, Dtvtston of Nurstng, Genettcs G IVF Instttute, 3020 Javter Road, Fatrfax, VA 22031. Shtrley L. Jones ts the Dtrector of Nurstng In the Dtvtston of Nurstng of the Genettcs G IVFlnstttute In Fairfax, VA.

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