Integrating Genetics and Genomics into Developmental Disabilities Nursing Practice

J. Carolyn Graff, PhD, RN, FAAIDD

Abstract

With the completion of sequencing the human genome in 2003, the Human Genome Project has laid the foundation for a focus on genomics. This article presents an overview of genetics and genomics, guidelines for integrating genetics and genomics into nursing practice, and resources to enhance nurses' knowledge and skills in this critical area of developmental disabilities nursing.

Keywords: genetics , genetic disorders , genetic nursing , genomics , genomic nursing , genome , pedigrees

INTRODUCTION

Nurses specializing in intellectual and developmental disabilities (I/DD) nursing have many opportunities to integrate the latest genetic advances into their practice. As direct care providers, consultants, administrators, educators, and researchers, nurses work to assure that persons with I/DD and their families receive comprehensive, lifelong care ¹. Nurses practice collaboratively with other professionals on interdisciplinary teams and often lead these teams either formally or informally. As genetic and genomic knowledge continues to increase, nurses can lead in applying this knowledge to support persons with I/DD and their efforts toward independence and self-determination. This paper provides an overview of genetics and genomics, presents guidelines for integrating genetic and genomic information into practice, and identifies resources nurses can use to increase their own knowledge of genetics and genomics and improve I/DD nursing practice.

GENETICS: THE BASIC ELEMENTS

Genetics is the study of biologically inherited traits that includes those traits that can be affected by the environment². Genes, transmitted from parents to their children, are located in chromosomes. Genes are found in the nuclei of almost all human cells, with the exception of red blood cells which do not have nuclei. Genes are also found in mitochondria, which are located outside the cell nucleus in cytoplasm. Interestingly, mitochondrial genes have a maternal pattern of inheritance, meaning the genes are inherited only from one's mother.

Each gene has a specific location or locus in the chromosome. Chromosomes are thread-like structures found in the nucleus of cells. Humans have 46 chromosomes or 23 chromosome pairs, with 22 pairs classified as autosomes and 1 pair classified as sex chromosomes. The sex chromosomes are the 23^rd chromosome pair and differ according to gender. Females have two X chromosomes (X,X) and males have an X and Y chromosome (X,Y).

During conception, humans receive matched pairs of chromosomes or one chromosome from each parent. Although pairs of chromosomes carry corresponding genetic information in similar sequences, the genetic sequence for each pair may not be identical. Since one chromosome is inherited from each parent, there are typically alleles or alternative copies of each gene on each chromosome. Alleles are homozygous when they are identical and heterozygous when they are different. For example, a homozygous allele is present when a person has type AA blood (one type A allele from each parent). A heterozygous allele can be found with type AB blood (an A allele from one parent and a B allele from the other parent).

DNA and the Human Genome

The human genome is the total set of genes that are carried by a person. Genes are made up of deoxyribonucleic acid or DNA. The building blocks of DNA are four nucleotide bases: adenine (A), cytosine (C), guanine (G), and thymine (T). A and G are purine bases, and C and T are pyrimidine bases. Purines and pyrimidines are complementary so that A always binds to T and C always binds to G. These bases are complementary and align so that each base along one strand of DNA is matched to a base in the opposite direction. These bases form the molecular structure of DNA, or double helix, that was described by James Watson and Frances Crick³.

The purine and pyrimidine bases in DNA contain information that is necessary for formation of proteins. Transferring genetic information from DNA into protein involves a multi-step process that includes several types of ribonucleic acid or RNA. In short, DNA codes for RNA and RNA codes for proteins. This route of transferring information from DNA to proteins is known as the "central dogma" of molecular genetics². The genome includes all the DNA in an organism or cell to include the 44 autosomes, 2 sex chromosomes, and the mitochondrial DNA. The complete set of proteins encoded in the genome is referred to as the proteome.

Mutations or changes in the genes or genetic material produce mutant RNA, which produces mutant protein. Inborn errors of metabolism, such as phenylketonuria (PKU), result from a genetic mutation, which leads to protein abnormality. That is, PKU results from the absence of or a defect in the enzyme, phenylalanine hydroxylase. PKU is a great example of the influence of the environment on the human genome and the importance of proper diagnosis, since clinical intervention through diet lessens the severity of PKU. When persons with PKU follow a diet with phenylalanine restriction, an intellectual disability can be prevented. If an intellectual disability already exists because PKU was undiagnosed, following a diet with phenylalanine restriction may prevent further deterioration but will not reverse an existing intellectual disability.

Mutations can be inherited or acquired. Hereditary mutations, such as cystic fibrosis or hemophilia A, are passed down through families. Acquired mutations refer to changes in the DNA that develop during a person's life during normal cellular changes or through environmental stresses such as radiation. Acquired mutations, such as many types of cancer, cannot be inherited. A careful family history using the pedigree chart will help distinguish between somatic and inherited mutations.

A mutation refers to a change in DNA sequence that has been identified in less than 1% of the population. A polymorphism is a change in DNA sequence that has been identified in more than 1% of the population. Mutations and polymorphisms determine a person's observable traits or phenotype. A person's genotype is the genetic makeup that is not evident as outward or visible characteristics.

The relationship between a person's phenotype and genotype is very important. For example, the notion that having a gene that is associated with a disorder predisposes that person to the disorder is not true. All humans have the same 20,000 to 25,000 genes. It is the mutation or polymorphism in the gene, not the gene, that predisposes a person to the disease or disorder. For example, each person has the cystic fibrosis transference regulator (CFTR) gene, but only those who develop cystic fibrosis have a mutation in the CFTR gene. Because all persons with cystic fibrosis are thought to have the CFTR genetic mutation, differences in severity of cystic fibrosis are thought to be related to other genetic and nongenetic factors⁴.

Types of Genetic Disorders

The three major categories for disorders that are caused to some degree by genetic factors include single-gene, chromosomal, and complex or multifactorial disorders. The respective prevalence of single-gene, chromosomal, and complex disorders for every 1000 persons by age 25 years is 3.6, 1.8, 46.4; after age 25 years is 16.4, 2.0, and 600; and over a lifetime is 20, 3.8, and 646.4⁵.

Single-Gene Disorders

Single-gene disorders are caused by a mutation or permanent structural change in DNA in a single gene. This mutation may be on one or both chromosomes in the pair. Single-gene disorders are usually recognized in childhood, with less than 10% manifesting after puberty⁴. Gregor Mendel identified the principles of heredity (Mendel's laws of inheritance) through his study of garden peas and their offspring. He noted that heredity units or genes were either recessive or dominant. The patterns of inheritance for single-gene disorders are autosomal recessive, autosomal dominant, X-linked recessive, and X-linked dominant. Cystic fibrosis, Ehlers-Danlos syndrome, neurofibromatosis, sickle cell disease, and Tay-Sachs disease are examples of single-gene disorders. A listing of single-gene phenotypes is available from Online Mendelian Inheritance in Man (OMIM^TM) (www/ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM).

Although most patterns of inheritance follow Mendel's laws, exceptions such as genomic imprinting and mitochondrial mutation inheritance do occur. Genomic imprinting results from differences in how the gene is expressed depending on whether a mutant allele is inherited from the mother or father. Examples of genomic imprinting are Prader-Willi syndrome (PWS) and Angelman syndrome. Almost 70% of persons with PWS have a deletion of the long arm of chromosome 15 that is inherited from their father. Persons with Angelman syndrome have a deletion in almost the same region on chromosome 15 that is inherited from their mother. For more information on genomic imprinting, go to http://mostgene.org/gd/gdvol10c.htm. Mitochrondrial mutations are transmitted from mothers to their sons and daughters; however, only daughters can pass their mitochrondrial DNA to their children. These children will inherit mitochrondrial mutations from their mother, but only daughters can pass these mutations on to their offspring. Examples of disorders with mitochondrial mutation inheritance include Leber's hereditary optic neuropathy, Leigh disease, and progressive sensorineural deafness induced by aminoglycoside antibiotics⁴. Additional information on mitochondrial inheritance can be found at http://mostgene.org/gd/gdvol10b.htm.

Chromosomal Disorders

Chromosomal disorders result from an abnormal chromosome number or structural rearrangements of chromosomes. Aneuploidy (the condition of having an extra chromosome or missing a chromosome) is usually due to an error in cell division in which a sperm or egg has too many or too few chromosomes. Most persons with aneuploidy have monosomy or trisomy. An example of monosomy (the presence of one chromosome instead of a pair of two chromosomes) is Turner syndrome (45, X). The most common type of trisomy (a third or extra chromosome instead of the pair of two chromosomes) is trisomy 21 or Down syndrome (47,XX or 47,XY). Chromosomal disorders can result from nondisjunction, deletions, or translocations. Helpful information on chromosome disorders can be retrieved from www.cafamily.org.uk/Direct/c30.html.

Complex Disorders

Complex or multifactorial disorders occur when small variations in genes, combined with environmental factors, result in a disorder or the increased susceptibility to a disorder. These disorders result from complex interactions between the genotype and environmental exposures that trigger, increase, or worsen the disorder. The pattern of inheritance is a complex or multifactorial pattern that does not follow the Mendelian pattern of inheritance⁴. Examples of complex disorders are Alzheimer disease, autism, cleft lip and palate, neural tube defects, schizophrenia, and Type 1 diabetes. Helpful overviews of complex disorders can be found through the National Human Genome Research Institute (NHGRI), www.genome.gov/10000865, or the University of Utah's Genetic Science Learning Center, http://learn.genetics.utah.edu/units/disorders/karyotype.

Pedigrees

A pedigree is a diagram of a family history that shows the family members and their relationship to the proband - the family member who has been identified as having a genetic disorder⁴. Pedigrees are helpful because they provide a visual display of how disorders and characteristics occur in a family and across generations of the family. Typically three-generation pedigrees are used by advanced practice genetic nurses, genetic counselors, and geneticists to identify risk for a disorder and plan a program to help prevent chronic conditions⁶. Commonly used pedigree symbols, definitions, and abbreviations⁷ can be found at http://mchneighborhood.ichp.edu/pacnorgg/GNW/GeneticFamilyHx.html and www.genome.gov/glossary.cfm?key=pedigree. Pedigrees of autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive disorders are shown in Figures 1-4.

Genetic Testing

Genetic tests are conducted by examining a person's blood, other body fluid, or tissue for biochemical, chromosomal, or genetic markers. The terms genetic testing and genetic screening may be used interchangeably. In some areas of practice, genetic screening refers to testing that identifies persons who are at higher risk of having or developing a genetic disorder, while genetic testing refers to those tests that are conducted for purposes of diagnosis. In this article, the term genetic testing refers to testing that determines a person's risk for a disorder, carrier status, diagnosis, and prognosis.

Tests may include molecular analysis of DNA and RNA, cytogenetics on chromosomes and biochemical analysis of proteins or certain metabolites. Prenatal genetic testing is used to identify genetic disorders such as Down syndrome through cytogenetic testing. Newborn screening programs in the U.S. are established on a state-by-state basis and typically include nine genetic disorders. The National Newborn Screening and Genetic Resource Center (http://genes-r-us.uthscsa.edu/) provides up-to-date information on tests required in each state. Carrier genetic tests are conducted to determine whether an unaffected person is carrying a gene that causes a certain disorder that could be transmitted to offspring. Diagnostic genetic testing is carried out on a person who has symptoms for the purpose of identifying the disorder and providing a prognosis. Predictive genetic testing is offered to a person who is asymptomatic yet is at-risk for a genetic disorder. Presymptomatic testing for prediction is conducted on a person who will eventually develop the symptoms if the gene mutation is present. Susceptibility testing for prediction is conducted on a person who is at-risk for developing the genetic disorder but for whom there is no certainty that the disorder will develop if the mutation is present. GeneTests is an online resource for health care providers on current genetic testing and its use in diagnosis, management, and genetic counseling (www.geneclinics.org).

Persons can benefit from genetic testing by having the opportunity for counseling and health promotion to reduce the risk of some disease conditions that have a known genetic basis. For example, when a person has a known genetic predisposition for high cholesterol, lifestyle changes can be made to decrease the likelihood that the condition will be expressed⁸. Results of genetic testing can be helpful when making decisions about the future, yet tests may reveal a diagnosis that has no treatment. Informed consent and counseling are necessary when conducting predictive genetic testing because of the ethical and legal issues that are involved. Issues related to discrimination, privacy, psychological impact, stigmatization, uncertainties associated with the interpretation of predictive genetics, and availability and access to testing and treatment need to be addressed for all persons. Some employers and insurance companies may misuse genetic information, creating challenges for persons with I/DD and their families who are striving for full inclusion⁹ and self determination¹⁰. Assuring that persons with I/DD understand the results of genetic testing and the implications of these results for themselves and their family members will require careful and thoughtful follow-up.

Emerging Therapies and Technologies

Persons with I/DD should have access to and benefit from emerging therapies and technologies. Therapies such as gene and stem cell therapy can improve health and may extend a person's life; however, critical issues such as who will have access to these expensive therapies need to be addressed. Pharmacogenomics, polymerase chain reaction (PCR), and microarray analysis allow practitioners to apply genetics to practice by identifying disease susceptibility genes, monitoring gene activity, and using genetic advances to improve a person's health. Pharmacogenomic testing will be increasingly used to prescribe the best medication and the best dosage of medication based on a person's genetic profile¹¹. Genome-wide association studies and genetic or linkage mapping are techniques being used to expand our understanding of the transmission of genetic disorders from parents to their offspring. Fact sheets about these technologies and research techniques can be found at the National Human Genome Research Institute URL: www.genome.gov/10000202. Informing persons with I/DD and their families about these therapies and technologies when appropriate is a responsibility of nurses and other health providers.

GUIDELINES FOR INTEGRATING GENETICS AND GENOMICS INTO PRACTICE

The International Society of Nurses in Genetics (ISONG), in collaboration with the American Nurses Association (ANA), has defined and established the scope of professional nursing practice in genetics from a global perspective in the document, Genetic/Genomic Nursing: Scope and Standards of Practice¹². Genetics specialty nursing practice is performed by basic or advanced level genetics nurses. Basic level genetics nurses have formal genetics clinical experiences from their basic nursing education programs or continuing education from professionals with specialty training in genetics. Advanced level genetics nurses are expected to be nurses with a graduate degree who practice genetics at an advanced practice level.

All registered nurses in the United States are expected to incorporate "genetic and genomic knowledge and skills" (p.12) into their nursing practice, as noted in the Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics⁶. By incorporating this knowledge and these skills into their practice, nurses should recognize when their own attitudes and values about genetics and genomics may affect nursing care; be able to advocate for access to appropriate services and resources; incorporate genetic and genomic technologies and information into their practice; and advocate for the rights of all persons to make autonomous and informed genetic- or genomic-related decisions. These essential genetic and genomic competencies for all registered nurses can be downloaded from www.nursingworld.org/ethics/genetics. In the United Kingdom, seven competencies for all nurses, midwives, and health visitors have been identified¹³. This framework of competencies defines the minimum knowledge, skills, and attitudes related to genetics that every nurse, midwife, and health visitor should possess.

Nurses should be able to assess persons with I/DD and their families who are affected by or at risk for a genetic disorder; identify diagnoses and expected outcomes; develop appropriate interventions; and evaluate progress made toward these outcomes. Nurses should have the knowledge and skills to generate a three-generation family health history and construct a pedigree. Therefore, nurses should develop a plan of care that integrates genetic and genomic information to improve the outcomes of persons with I/DD and their families.

GENETIC AND GENOMIC RESOURCES

Resources to improve nurses' genetic and genomic knowledge and skills can be found in books and monographs, through continuing education offerings, post-graduate education programs, and Internet sites⁶. Just as faculty are increasing content on genetics and genomics in the curriculum of undergraduate and graduate nursing education programs, practicing nurses must be increasing their participation in continuing education offerings on genetics and genomics. All nurses working in the field of I/DD could benefit from a center such as the National Genetics Education and Development Center, www.geneticseducation.nhs.uk. This Center serves as a central resource for genetics and genomics education of health professionals in the United Kingdom.

Genetics nursing practice has been expanding in Canada, Japan, the United Kingdom, and the United States and is evolving in Brazil, Israel, and Italy. Nurses' contribution to specialist genetics health care is well established in Australia, Belgium, the Netherlands, and New Zealand¹². Regardless of the developmental stage of genetic nursing practice in a given location, educational offerings and online resources are increasingly available. Some of these offerings and resources are listed in Table 1. And, organizations such as ISONG have been established to support the scientific and professional growth of nurses in human genetics and genomics around the world (www.isong.org).

CONCLUSIONS

Translating knowledge of genetics and genomics into health benefits through improved health was one of the major themes proposed by the National Human Genome Research Institute as the genomic era emerged and the Human Genome Project ended¹⁴. Nurses are increasingly expected to use genetic and genomic information and technology to improve the health of persons receiving their care. Since essentially all diseases and conditions have a genetic or genomic component⁸, nurses specializing in I/DD are providing care to many persons who have a known or sometimes unidentified genetic disorder. Persons with I/DD who have a known genetic disorder may be predisposed to a health problem that is related to the genetic disorder but could be minimized by lifestyle changes, such as changes in diet or activity level. Persons with I/DD may have received a genetic evaluation in early childhood but may not have had the opportunity for a more recent evaluation based on genetic and genomic advances. Likewise, parents and siblings may have no or little understanding of their family member's genetic disorder yet could benefit physically, emotionally, and psychologically from gaining more accurate information. Since a number of I/DD are the result of germline mutations (mutations involving reproductive cells, e.g., ovum and sperm), persons with I/DD and their family members should have access to information about the genetic disorder so they may make informed reproductive choices.

As persons with I/DD live longer and genetic and genomic information and technology continue to increase, nurses have a responsibility to learn about these advances and integrate genetic and genomic information and technology in their every day practices. Nurses specializing in I/DD have been described as providing care and education to persons with I/DD and their families with passion¹⁵. Adapting to the changes and advances in science, nurses can use their passion to be at the forefront of translating genetic and genomic information and technology into improved care and health outcomes for persons with I/DD and their families.

Table 1. Genetic and Genomic Resources for Nurses

Books
American Nurses Association and International Society of Nurses in Genetics. Genetics/Genomics Nursing: Scope and Standards of Practice. Silver Spring (MD): Nursebooks.org; 2007. Consensus Panel on Genetic/Genomic Nursing Competencies. Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics. Silver Spring (MD): American Nurses Association; 2006. Jenkins JF, Lea DH. Nursing Care in the Genomic Era: A Case-Based Approach. Boston: Jones and Bartlett; 2005. Lashley FR. Essentials of Clinical Genetics in Nursing Practice. New York (NY): Springer Publishing; 2006. Monsen RB. Genetic Nursing Portfolios: A New Model for the Profession. Silver Spring (MD): Nursebooks.org; 2005. Olsen S, Baxendale-Cox L, Mock V, editors. The Nursing Clinics of North America. Clinical Genetics. 2000 Sept; 35(3). Skirton H, Patch C. Genetics for Healthcare Professionals—A Lifestage Approach. Oxford: Bios Scientific Publishers; 2002.
Continuing Education
Annual Meeting. International Society of Nurses in Genetics, Inc. (ISONG). www.isong.org/ Genetics Education Program for Nurses. Web-Based Genetics Institute and Genetics Program for Nursing Faculty. Cincinnati Children's Hospital Medical Center. www.cincinnatichildrens.org/ed/clinical/gpnf National Coalition of Health Professional Education in Genetics (NCHPEG). www.nchpeg.org/ Summer Genetics Institute. National Institute of Nursing Research (NINR). www.ninr.nih.gov/Training/TrainingOpportunitiesIntramural/SummerGeneticsInstitute/
Genetics 101 or Genetic Basics
Centre for Education in Medical Genetics. www.bwhct.nhs.uk/genetics-cemg-home.htm Centre for Genetics Education. www.genetics.com.au/ Dolan DNA Learning Center. www.dnalc.org Genetics Education Center. www.kumc.edu/gec/ National Human Genome Research Institute (NHGRI) All About the Human Genome Project. www.genome.gov/10001772 Fact Sheets. www.genome.gov/10000202 Talking Glossary of Terms. www.genome.gov/glossary.cfm National Public Radio, The DNA Files. www.dnafiles.org
Genetic Disorders
Genetics and Rare Conditions Site. www.kumc.edu/gec/support National Cancer Institute. www.nci.nih.gov/ National Library of Medicine, Genetics Home Reference. http://ghr.nlm.nih.gov/ Online Mendelian Inheritance in Man. www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=omim
Nursing Practice
American Medical Association. Family History Tools: The Importance of Gathering a Family History. www.ama-assn.org/ama/pub/category/2380.html GeneReviews and GeneTests. www.geneclinics.org Genetic Science Learning Center. http://gslc.genetics.utah.edu Genomics and Disease Prevention, Office of Genomics and Disease Prevention. CDC. www.cdc.gov/genomics/default.htm My Family Health Portrait. https://familyhistory.hhs.gov/ National Human Genome Research Institute (NHGRI). Issues in Genetics and Health. www.genome.gov/10001740 The Ethical, Legal, and Social Implications (ELSI) Research Program. www.genome.gov/10001618 Research Ethics and Stem Cells. http://stemcells.nih.gov/info/ethics.asp