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Learning Objectives
• Define genomic healthcare.
• Describe the role of genes in health and
disease.
• Describe three new genomic research efforts.
• Discuss the nursing role in family history
assessment.
• List two new ways that genetic testing is being
used in pediatric practice.
• Identify ethical issues of concern with regard to
genomic healthcare.
1
Yesterday’s Genetics
• Chromosomes – units of heredity inside
cells – first discovered in the late 1800’s.
• Early 1900’s – inherited diseases first
linked to chromosomes.
• !950’s – 1980’s – genetic tests for genetic
conditions affecting children such as cystic
fibrosis, Down syndrome and Duchenne
muscular dystrophy were developed.
Yesterday’s Genetics
• Genetic testing used to make or confirm a
diagnosis, and to screen newborns for
conditions such as PKU so early
interventions and treatments could be
administered.
• Very few research laboratories capable of
conducting genetic testing, and few
commercial genetic testing
laboratories.
2
Today’s Genetics and Genomics
• NHGRI lead the Human Genome Project
for the National Institutes of Health.
• The full human genome sequence was
completed in April 2003.
• NHGRI now moves forward into the
genomic era with research aimed at
improving health and fighting disease.
3
Personalized Medicine
• Pre-genome era: healthcare providers
used a “one size fits all” approach to
treating individuals.
• Post-genome era: increasingly healthcare
providers will be able to use genomic
information to tailor treatments to the
individual, and personalize their care.
4
Essential Nursing Competencies and
Curricula Guidelines for Genetics and
Genomics
• Established by Consensus Panel in 2005
• Professional Responsibilities for all registered
nurses:
– Incorporate genetic and genomic technologies and
information into registered nurse practice.
– Demonstrate in practice the importance of tailoring
genetic and genomic information and services to
clients based on their culture, religion, knowledge
level, literacy and preferred language.
5
Understanding Basic Genetics: A
First Step
• A gene is the basic physical and functional unit of heredity.
• Genes, which are made up of DNA, act as instructions to make
molecules called proteins.
6
DNA - RNA - Protein
• The journey from gene to protein is complex and tightly controlled
within each cell. It consists of two major steps: transcription and
translation.
7
U.S. Surgeon General’s Family History
Initiative
• “Tracing the illnesses suffered by your
parents, grandparents, and other blood
relatives can help your doctor predict the
disorders to which you may be at risk and
take action to keep you and your family
healthy.”
8
U.S. Surgeon General’s Family History
Initiative
• HHS agencies involved in this project
include:
– National Human Genome Research Institute
(NHGRI) at the National Institutes of Health,
– Centers for Disease Control and Prevention
(CDC),
– the Agency for Healthcare Research and
Quality (AHRQ)
– Health Resources and Services
Administration (HRSA).
9
Family History Collection: Nursing
Roles
• Inform patients of the importance of family
history in health and disease.
• Introduce families to the Surgeon
General’s Family History Tool
• Assist with collection of family history from
families
• Construct 3-generation pedigree
• Refer families at risk for further evaluation
and counseling
• Autosomal Dominant
• Autosomal Recessive
• X-linked
• Mitochondrial
10
Autosomal Dominant Inheritance
11
Autosomal Recessive Inheritance
12
X-linked Inheritance
X-linked Inheritance
Pedigree Illustrating X-Linked Recessive Inheritance Pattern
13
X-linked Inheritance
X-linked Inheritance
14
X-linked Inheritance
X-linked Inheritance
15
Mitochondrial Inheritance
• Also known as maternal inheritance.
• Mitochondria are structures in each cell that convert
molecules into energy, and each contain a small amount
of DNA.
• Only egg cells contribute mitochondria to the developing
embryo.
• Only females can pass on mitochondrial conditions to
their children Mitochondrial disorders can appear in
every generation of a family and can affect both males
and females, but fathers do not pass mitochondrial traits
to their children.
• Example: Leber hereditary optic neuropathy (LHON) an
inherited form of vision loss.
Mitochondrial Inheritance
16
Case Example: Family History
Assessment
• Mrs. G provides you with this family history
during her son’s annual pediatric visit. Her sister
recently had a baby who was born with cystic
fibrosis (CF). She has questions about how this
happened in her family and what it means for
her and her husband when they have another
baby.
17
Emerging Genetic and Genomic
Research
• Essential Nursing Competency:
Incorporate genetic and genomic
technologies and information into
registered nurse practice.
18
Cancer Genome Atlas (TCGA)
• TCGA is a comprehensive and coordinated effort to
accelerate understanding of the molecular basis of
cancer.
• Involves application of genome analysis technologies,
including large-scale genome sequencing.
• TCGA is a joint effort of the National Cancer Institute
(NCI) and the National Human Genome Research
Institute (NHGRI),
• Mission and Goal
– TCGA will assess the feasibility of a full-scale effort to
systematically explore the entire spectrum of genomic
changes involved in human cancer.
– The overarching goal of The Cancer Genome Atlas is
to improve our ability to diagnose, treat and prevent
cancer.
19
Office of Population Genomics
• Establishes research resources to identify
genes related to complex diseases and
their environmental modifiers.
20
Office of Population Genomics
Research Program Priorities
• Policy for Sharing of Data Obtained in NIH
Supported or Conducted Genome-Wide
Association Studies (GWAS):
– Developed following a public consultation
process with interested stakeholders, the
GWAS data-sharing policy will facilitate the
research community’s access to genotype
datasets from GWAS in a broad array of
disease areas.
21
Human Genome Clinical Research
• Examples of disorders under study:
– Attention Deficit Hyperactivity Disorder
(ADHD)
– Various disorders of the immune system
– Holoprosencephaly – a common brain
malformation
– Alkaptonuria – a devastating joint disease in
adults
– Neurofibromatosis
22
Human Genome Clinical Research
• NHGRI clinical researchers have played a
key role in a number of important gene
discoveries:
– Identification of a gene that causes a kidney
disorder called Hartnup disease.
– Identification of genes responsible for
holoprosencephaly.
23
The ClinSeq Project
• Studying large-scale medical sequencing
in a clinical research setting.
• Specific regions of a research participants’
genome will be sequenced, and relevant
results returned to that person.
• Investigators will then look into the various
medical, technical, genetic counseling
issues that accompany the implementation
of this testing in the clinical setting.
ClinSeq Project
• Genome sequencing test may find changes in a
participant’s gene that cause or contribute to
disease.
• Participants may learn about changes in a gene
or genes that has caused symptoms of a
disease, or that they have variations that may
cause them to develop a disease in the future.
• Participants will be followed for a number of
years by researchers to learn about how
identified genes affect their health and
development of disease.
24
Multiplex Initiative
• A research project conducted by NHGRI
and NCI.
• Collaboration with the Group Health
Cooperative in Seattle, and Henry Ford
Health System in Detroit.
• Investigating the interest level of healthy,
young adults in receiving genetic testing
for eight common conditions.
Multiplex Initiative
• Genetic test will provide information about 15 different
genes that play a role in:
– Type 2 diabetes
– Coronary heart disease
– High blood cholesterol
– High blood pressure
– Osteoporosis
– Lung cancer
– Colorectal cancer
– Malignant melanoma
• Investigating how young adults who choose to take the
tests interpret and use the results in making their own
health care decisions in the future.
25
Multiplex Initiative
• As noted by NHGRI Scientific Director,
Eric Green, MD, PhD –
– “The Multiplex Initiative will provide insights
that will be key to advancing the concept of
personalized medicine.”
Genetic Testing
• Nursing Competency: Demonstrates an
understanding of the relationship of genetics to
health, prevention, screening, diagnostics,
prognostics, selection of treatment, and
monitoring of treatment effectiveness.
26
Genetic Testing
• Diagnostic genetic testing – identifies a genetic
condition or disease that is making or in the
future will make a person ill.
• Examples:
– Chromosome analysis to diagnose Down syndrome.
– Gene testing to diagnose Sickle Cell Anemia
– Gene testing for Achondroplasia, a disorder of bone
growth
Genetic Testing
• Predictive and presymptomatic genetic testing
• Examples:
– Gene testing for Huntington Disease
– Gene testing for hereditary breast and ovarian cancer
(BRCA1/BRCA2)
– Multiplex genetic testing to identify risk for common
diseases such as diabetes, heart disease, and stroke
27
Genetic Testing
• Carrier testing – tells people if they “carry” a
genetic change that can cause a disease.
• Carriers usually show no signs of the disease.
• Carriers can pass on the genetic variation to
their children, who may develop the disorder or
become carriers themselves.
• Examples:
– Cystic fibrosis
– Sickle cell anemia
– Tay-Sachs disease
Genetic Testing
• Prenatal testing – offered during pregnancy to
help identify fetuses that have certain diseases
such as spina bifida.
28
Genetic Testing
• Pre-implantation genetic testing – is done in
conjunction with in vitro fertilization to determine
if embryos for implantation carry genes that
could cause disease such as Tay-Sachs
disease.
Genetic Testing
• Research genetic testing – helps scientists learn
more about how genes contribute to health and
disease, as well as develop gene-based
treatments.
• Examples:
– Genetic Analysis of Attention Deficit Hyperactivity
Disorder? NHGRI Research
– Genetic Analysis of Neural Tube and Orofacial Cleft
Defects in the Irish Population
– http://www.genome.gov/10004414
29
Genetic Testing
• Pharmacogenetic genetic testing –
– examines a person's genes to look at how
drugs would move through the body and be
broken down.
– The goal of pharmacogenetic testing is to
have drug treatments that are specific to each
person.
Genetic Testing
• Pharmacogenomic genetic testing –
– examines the inherited variations in genes
that dictate drug response, and
– explores the ways these variations can be
used to predict whether a patient will have a
good response to a drug, a bad response to a
drug, or no response at all.
30
Genetic Testing
Is there a difference between pharmacogenomics
and pharmacogenetics?
• Pharmacogenomics refers to the general study of all of
the many different genes that determine drug behavior.
Personalized Medicine
• Personalized medicine has the potential to
transform healthcare through:
– earlier diagnoses,
– more effective prevention and treatment of
disease,
– avoidance of drug side effects.
31
Clinical Pharmacogenetics in
Pediatric Patients
• Transplantation – Clinical Effects of Drug Concentration
– Patients with the MDR1 (ABCB1) genotype require more
aggressive alternative treatment regimes when being weaned
from corticosteroid immunosuppressive therapy.
Clinical Pharmacogenetics in
Pediatric Patients
– Childhood Leukemia – Drug Response and Toxicity
– Acute Lymphoblastic Leukemia (ALL)
• Treatment with 6-mercaptopurine (6MP) is a key medication for
treatment of ALL.
• Thiopurine methyltransferase (TMPT) helps to metabolize 6MP
• Studies have shown that TMPT genotype or phenotype identifies
patients who are at risk for hemopoietic toxicity after thiopurine
therapy.
• For example, patients who have TMPT deficiency are at very high
risk of sever hematopoetic toxicity if treated with the conventional
doses of thiopurines
• Therefore there is great clinical benefit in determining an ALL
patient’s TMPT genotype before administering the treatment in all
children – more effective drug therapy and less potential toxicity for
patients
32
Clinical Pharmacogenetics in
Pediatric Patients
– Asthma – most common chronic disorder in children
and adolescents, and leading cause of
hospitalizations in children.
– Albuterol (an inhaled B2 agonist) commonly used
treatment.
– Studies are now underway looking at how an asthma
patient’s genotype affects response to Albuterol, and
how doses can be modified based on genotype.
Clinical Pharmacogenetics in
Pediatric Patients
– Attention-deficit hyperactivity disorder (ADHD) – a
common childhood disruptive disorder, characterized
by age inappropriate levels of inattention,
hyperactivity and impulsivity.
– Studies are underway that look at children’s
genotypes to be able to predict medication tolerability
and side effects.
– Awareness of increased risk for particular side effects
may lead clinicians to choose medications that are
more likely to be tolerated long term, and avoid
exposing patients to drugs with high chance of poor
outcomes.
33
Clinical Pharmacogenetics in
Pediatric Patients
– Francis Collins’ Research in Progeria, a rapid aging
disease in children that results in eventual death
around 12 or 13.
– The disease results in a toxic protein that causes a
heart attack.
– Discovered a drug that may be beneficial. In studies
of mice, the drug completely cured the affected mice.
– Current clinical trials underway with 28 children.
Genetic Testing
• Direct-to-consumer genetic testing – a new
approach that allows people to order certain
genetic tests by sending in a sample of their
saliva or tissue to a laboratory.
• The laboratory returns results only to the
individual who sent in the sample.
• Often no healthcare provider is involved in the
process.
34
Genetic Testing
• Direct-to-consumer genetic testing – should
children have their genomes scanned?
– Proactive family project – earlier opportunities for
intervention and prevention?
– Informed consent?
– The DNA Innate Talent Test – testing children to
identify genetic traits for intelligence, emotional
quotient (EQ), athletic ability?
35
Teaching Patients and Families About
Genetic Testing: Nursing Roles
• The registered nurse:
– Provides clients with interpretation of selective
genetic and genomic information or services.
– Provides clients with credible, accurate, appropriate,
and current genetic and genomic information,
resources, services, and/or technologies that facilitate
decision-making.
– Uses genetic- and genomic-based interventions and
information to improve clients’ outcomes.
» Essential Nursing Competencies and
Curricula Guidelines for Genetics and Genomics, 2006
36
Teaching Patients and Families About
Genetic Testing: Nursing Roles
• Refer client for genetic counseling to get more
information about the genetic test.
• Provide resources to the client about where they
can learn more about genetic testing:
– National Human Genome Research Institute –
www.genome.gov/health
– Genetics Home Reference –
http://ghr.nlm.gov/medlineplus/genetictesting.html
– National Cancer Institute –
www.cancer.gov/cancertopics/UnderstandingCancer/
genetesting
37
Health Issues in Genetics and
Genomics
• Genomic research – designed to advance
understanding of the human genome and the
role of individual genes or groups of genes in
human health to improve the medical
community’s ability to treat and cure diseases.
• Genomic research – also raises questions about
how the information and technologies it yields
will affect standards of patient care.
38
Ethical Issues in Genetics and
Genomics
• NHGRI supports highly technical genomic
research that is rapidly advancing our
understanding of the human genome.
• New information is potentially beneficial to the
health of Americans, BUT it can also be
misused.
• Ethical, Legal and Social Issues (ELSI) Branch
of NHGRI informs the development of federal
guidelines, regulation and legislation to guard
against misuse of genetic information.
39
ELSI Health Issue Areas
• Direct-to-Consumer Marketing of Genetic
Tests – may increase public awareness
but there may also be some risks in
adopting this strategy.
• A Government Accountability Study (GAO)
concluded that direct-to-consumer genetic
tests pass on “misleading” information.
40
ELSI ISSUES
• Privacy and Confidentiality of Genetic and
Genomic Information
Genetic Information
Nondiscrimination Act (GINA)
• Genetic Information Nondiscrimination Act (GINA)
• May 21,2008 — The President signed into GINA into
law.
• GINA protects Americans against discrimination based
on their genetic information when it comes to health
insurance and employment.
• The long-awaited measure, which has been debated in
Congress for 13 years, will pave the way for people to
take full advantage of the promise of personalized
medicine without fear of discrimination.
41
What GINA Does and Does Not Do
• What GINA does - The law protects
people from discrimination by health
insurers and employers on the basis of
DNA information.
• What GINA does not do - The law does
not cover members of the military. In
addition, the law does not cover life
insurance, disability insurance and long-
term care insurance.
42
Genetic and Genomic Resources for
Patients and Health Professionals
• Genetics and Rare Diseases Information
Center (GARD)
– www.genome.gov/Health/GARD
– E-mail: gardinfo@nih.gov
– Toll-free phone: 1-888-205-2311
– TTY: 1-888-205-3223
– This free service provides information about
genetic and rare diseases and refers people
to reliable sources of information in English
and in Spanish.
43
Genetic and Genomic Resources for
Patients and Health Professionals
44
Genetic and Genomic Education
Resources
45
Summary
• The pace of genomic research is transforming
our understanding of the role of genetics and
genomics in health and disease.
• It is now known that genomics plays a role in 9
out the 10 leading causes of death.
• All human beings are 99.9 percent identical in
their genetic makeup.
• Differences in the remaining 0.1% hold
important clues about the causes of both health
and disease.
46