SARAH LEWIS PA-C

Ethics of Genetics Testing

Objectives

Upon completion of this discussion the PA student will: Define Eugenics and list historic precedents that have

influenced American culture, values and laws regarding genetic testing

Discuss the issues related to genetic testing and the use/misuse of genetic information

Describe the value of genetic tests and further state a case for personalized healthcare

Describe the purpose of the Human Genome Project and identify resources related to defining the human genome

Critically evaluate the current laws related to genetic testing Differentiate between embryonic and stem cells lines

obtained from other sources. Describe the value and problems with each

Analyze the current debate over federal funding for new stem cell lines and articulate an argument for or against federal funding for stem cell research

Eugenics

Define Eugenics is the study and practice of selective breeding applied

to humans, with the aim of improving the species Eu= good or well; genes= born

Positive eugenics encourages reproduction among the “genetically advantaged”

Negative eugenics lowers fertility among the “genetically disadvantaged”

Can you guess how this has been applied historically?

Eugenics in History

Ancient cultures infanticide- Rome, Sparta1880’s-1930s and beyond: eugenic policy to

sterilize certain mental health patients in the US, Belgium, Brazil, Canada, Sweden and others

Nazi Germany: racial ‘hygiene’, human experimentation and extermination

Swedish eugenics until 1975

Human Genome Progect

identify and map the approximately 20,000–25,000 genes

~8% remains, including the telomeres, centromeres, loci, and heterochromatin

Headed by James Watson and the NIH in 1990, Francis Collins in 1993

OMIM= Online Mendelian Inheritance in Man ®

http://www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM information on all known mendelian disorders and over 12,000

genes phenotypes and genotypes

Value of Genetic Tests

Diagnostic preimplantation genetic diagnosis prenatal diagnostic testing newborn screening confirmational diagnosis of a symptomatic individual forensic/identity testing

Predictive carrier screening proactive healthcare

presymptomatic testing for predicting adult-onset disorders

Prenatal Genetic Screening

Chorionic villus sampling (CVS) between 10 and 12 weeks of pregnancy the villus cells in the placenta have the same genetic

composition as the cells in the fetus's tissuesOther techniques looking for embryonic cells in a

mother's blood and plasma In development still safe and relatively inexpensive cytogenetic analysis

Preimplantation genetic diagnosis = PGD a single cell, or blastomere, is removed from an embryo that

has been fertilized in vitro, and this cell is tested for genetic abnormalities

If passes tests the rest of the embryo can then be transferred to the mother's uterus

Fertility Ethics

embryo-harvesting techniques associated with IVF

excess embryos after PGD Cryopreservation? donate their embryos to stem cell research? donate to another IVF candidate ? embryos as a marketable commodity?

Newborn Genetic Screening

small blood sample is collected from newborn infants within 24 hours of birth and tested for a panel of disorders.

Between 3-40 tests(MedlinePlus, 2008) depending on geographic region

can save an infant's life- early diagnosis and treatment are imperative for a good outcome.

phenylketonuria (PKU)-unable to properly metabolize the amino acid phenylalanine diet that is low in phenylalanine

Testable Genetic Diseases

Alpha-1-antitrypsin deficiency (AAT; emphysema and liver disease) Amyotrophic lateral sclerosis (ALS; Lou Gehrig's Disease; progressive motor function loss leading to paralysis and death) Alzheimer's disease* (APOE; late-onset variety of senile dementia) Ataxia telangiectasia (AT; progressive brain disorder resulting in loss of muscle control and cancers) Gaucher disease (GD; enlarged liver and spleen, bone degeneration) Inherited breast and ovarian cancer* (BRCA 1 and 2; early-onset tumors of breasts and ovaries) Hereditary nonpolyposis colon cancer* (CA; early-onset tumors of colon and sometimes other organs) Central Core Disease (CCD; mild to severe muscle weakness) Charcot-Marie-Tooth (CMT; loss of feeling in ends of limbs) Congenital adrenal hyperplasia (CAH; hormone deficiency; ambiguous genitalia and male pseudohermaphroditism) Cystic fibrosis (CF; disease of lung and pancreas resulting in thick mucous accumulations and chronic infections) Duchenne muscular dystrophy/Becker muscular dystrophy (DMD; severe to mild muscle wasting, deterioration, weakness) Dystonia (DYT; muscle rigidity, repetitive twisting movements) Emanuel Syndrome (severe mental retardation, abnormal development of the head, heart and kidney problems) Fanconi anemia, group C (FA; anemia, leukemia, skeletal deformities) Factor V-Leiden (FVL; blood-clotting disorder) Fragile X syndrome (FRAX; leading cause of inherited mental retardation) Galactosemia (GALT; metabolic disorder affects ability to metabolize galactose) Hemophilia A and B (HEMA and HEMB; bleeding disorders) Hereditary Hemochromatosis (HFE; excess iron storage disorder) Huntington's disease (HD; usually midlife onset; progressive, lethal, degenerative neurological disease) Marfan Syndrome (FBN1; connective tissue disorder; tissues of ligaments, blood vessel walls, cartilage, heart valves and other structures

abnormally weak) Mucopolysaccharidosis (MPS; deficiency of enzymes needed to break down long chain sugars called glycosaminoglycans; corneal clouding,

joint stiffness, heart disease, mental retardation) Myotonic dystrophy (MD; progressive muscle weakness; most common form of adult muscular dystrophy) Neurofibromatosis type 1 (NF1; multiple benign nervous system tumors that can be disfiguring; cancers) Phenylketonuria (PKU; progressive mental retardation due to missing enzyme; correctable by diet) Polycystic Kidney Disease (PKD1, PKD2; cysts in the kidneys and other organs) Adult Polycystic Kidney Disease (APKD; kidney failure and liver disease) Prader Willi/Angelman syndromes (PW/A; decreased motor skills, cognitive impairment, early death) Sickle cell disease (SS; blood cell disorder; chronic pain and infections) Spinocerebellar ataxia, type 1 (SCA1; involuntary muscle movements, reflex disorders, explosive speech) Spinal muscular atrophy (SMA; severe, usually lethal progressive muscle-wasting disorder in children) Tay-Sachs Disease (TS; fatal neurological disease of early childhood; seizures, paralysis) Thalassemias (THAL; anemias - reduced red blood cell levels) Timothy Syndrome (CACNA1C; characterized by severe cardiac arrhythmia, webbing of the fingers and toes called syndactyly, autism)

BRCA1 and BRCA2

5-10% of Brest Cancers are genetic mutations on the BRCA1 and BRCA2 up to an

85% greater lifetime chance of developing breast cancer than women with unaffected genes

increased risk of ovarian, pancreatic, gastric, or prostate cancers than people without the mutations.

People of Ashkenazi Jewish descent have a higher incidence of inheriting these

Prophylactic surgery?Increased screening?Chemoprevention?

Hereditary Nonpolyposis Colerectal Cancer (HNPCC)

5 percent of colorectal cancer patients have an inherited form of the disease

Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, results in an increased risk of colon cancer and other cancers—specifically, endometrial and ovarian cancers in women; gastric cancer; and urinary tract cancer.

HNPCC presents few symptoms in early stages. germline mutation on any of several mismatch repair

genes, whose job it is to prevent DNA errors during replication: hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6. People who have inherited an altered mismatch repair gene have about a 70 percent to 80 percent lifetime chance of developing colon cancer.

Early colorectal screenings, removal of precancerous Screening for other cancers associated with the condition.

Familial Adenomatous Polyposis (FAP)

A second type of hereditary colon cancer, familial adenomatous polyposis, or FAP, involves a mutation of the adenomatous polyposis coli (APC) gene on chromosome 5.

The APC gene’s role is to control cell growth. FAP causes hundreds of polyps to grow, often starting when

patients are in their teens, which then become cancerous. If an FAP patient does not seek treatment, there’s a nearly

100 percent chance he or she will develop colon cancer by age 45.

removing the colon may be the only choiceResearchers continue to search for an effective medical

treatment.

Long QT Syndrome

LQT3 gene, on chromosome 3, are prone to abnormal heart rhythms while they are asleep.

mutated on chromosome 11 arrhythmia while the person is under stress.

mutation on chromosome 21 arrhythmia when a person is exercising.

prescribed beta-blockers, which can slow the heart rate as long as they take it

Pacemaker or defibrillator may be needed

Genetics and the Law

GINA: The Genetic Information Nondiscrimination Act of 2008 prohibits discrimination in health coverage and

employment based on genetic information However insurers can increase rates

do not apply to employers with fewer than 15 employees

do not extend to life insurance, disability insurance and long-term care insurance.

does not mandate coverage for any particular test or treatment.

Genetics and the Law Topics

Diagnostic Testing and the Ethics of Patenting DNA Intellectual property rights offset the financial risks of funding research but limit information access. Can a balance between private interests and public desire for treatments be achieved?

Protecting Your Genetic Identity: GINA and HIPAA Genomics could enable the misuse and abuse of our most personal information. On the other hand, could genetic privacy acts like GINA and HIPAA close the shutters on progress in health research?

Forensics, DNA Fingerprinting, and CODIS How ethical is it to keep a database of convicted felons' DNA profiles? Can we rely on DNA fingerprints for conviction? Many ethical issues surround the use of DNA in forensic technology.

Legislative Landmarks of Forensics: California v. Greenwood and Shed DNA Everywhere we go, we leave our DNA behind. Forensics profits from this “abandoned” DNA to solve crimes. As technology improves, could we wind up with a database of everyone’s DNA – including yours?

Sports, Gene Doping, and WADA Gene doping could stretch the physical limits of human strength and endurance. What are the consequences of gene therapy in sports competition, and more, importantly, is it safe?

 

Small group discussion:Reproductive and Other Familial Concerns

“Should a carrier of a known genetic risk be obligated to tell his or her relatives (Forrest et al., 2007; Gaff et al., 2007)? Although some people feel that an individual who is

found to carry a dominant gene for Huntington's disease has an ethical obligation to disclose that fact to his or her siblings, there currently is no legal requirement to do so.

In fact, requiring someone to communicate his or her own genetic risk to family members who are therefore also at risk is considered by many to be ethically dubious.”

Small group discussion:Reproductive and Other Familial Concerns

In the case of HD, although there is no way to treat or prevent this condition, knowing one's status could influence many life decisions. Would you have chilren?

Use PGD? Still get tested if you have children? If predicted to have symptoms at age 40 how would this

affect how you live your life? What if you were cleared by testing but your kids and

siblings were not? Not get tested at all?

“Research has shown that individuals with a family history of genetic disorders who know they are at risk but choose not to get tested can have difficulties in social interactions (McConkie-Rosell et al., 2008).”

Genetic Testing Open to the Public

http://www.pbs.org/wnet/religionandethics/episodes/september-4-2009/personalized-genetic-testing/4113/

8 ½ minute video from PBS

Personalized Genetics Testing

Health insurance coverage/denial GINA to prevent discrimination

Employers knowledge of predispositions

Stem Cell Differences

Embryonic stem cells have the ability to differentiate into any type of cell

Adult stem cells are specializedInduced Pluripotent Stem Cells- reversed

specialized cells differentiation- host specific

Neuroprogenitors unable to be extracted from adult lines thus far

Use of embryos for stem cell lines murder?

Does the possibility of curing spinal cord injuries or Parkinson’s outweigh this?

As genetics allows us to turn the tide on human disease, it's also granting the power to engineer desirable traits into humans. What limits should we create as this technology develops?

GATTACA Movie

http://www.youtube.com/watch?v=o7OYCmynrRU&feature=related

2 ½ minute trailer on YouTube

The End