1. The Significance of Genetics Across Disciplines: Genetic Counseling & Testing
Rachel Bertsch

2. Overview What is a gene? How do we learn about genes?
What is genetic testing and why is it important?
What are genetic disorders?
What kinds of genetic tests are available?
What are some of the obstacles and concerns with genetic testing?
What is genetic counseling?
How does someone become a genetic counselor?
Recap, Resources

3. What is a gene? What does it do?
A gene is the basic unit of heredity
Genes are short segments of deoxyribonucleic acid (DNA) found in the chromosomes of all cells
Each gene contains a code that directs the construction of essential molecules called proteins
Nucleus
Cell
Chromosome
Gene
DNA
There are roughly 25,000 genes in humans. Each person has two copies of a gene, one from their mother and one from their father. These proteins make up who we are and our characteristics like the color of our hair, height, and any conditions we may have. Much of the understanding and knowledge we have today about genes and genetics comes from genetic research; particularly those that utilize animal models.

4. Animal Models for understanding the genetic code
Animals have been invaluable to the study of genetics and understanding disease
Mice, rats, primates, zebrafish and a whole host of other organisms make incredible discoveries possible
Many diseases we understand today were first characterized and understood in animal models
Zebrafish are especially useful due to their see-through embryos allowing us to watch as genes and disease are expressed in vivo
The mouse is the most widely used model of human disease

5. Human Genome Project
International, cooperative effort to sequence the entire human genetic code of roughly 3 billion base pairs.
Started in 1990
Completed in 2003, ahead of schedule and under budget
All results made available online as they were sequenced
Now over 1800 genes coding for disease have been discovered
And over 2000 (and counting) genetic tests have been developed
The Human Genome Project paved the way for genetic testing and a better understanding of human disease. By sequencing all of the base pairs found in DNA, the adenine, thymine, cytosine, and guanine making up the genetic code, we have gained much knowledge about gene location, structure and function. While we do not know the identity of all genes and their purpose yet, this is something that research is consistently working toward. The genetic tests we have available now are the fruits of those labors.

6. What is genetic testing?
Taking a sample of DNA and sequencing the genes to determine the genetic code
Mutations are changes in the genetic code that can be harmful or beneficial
Some mutations can cause diseases, in this case, genetic conditions
We can get a sample of DNA typically from a blood draw. In the case of testing a fetus we can take a sample from the placenta. Genetic tests can detect a variety of mutations in the genetic code, with varying levels of sensitivity depending on the type of testing done. Because of previous research we now know what kinds of mutations cause what kinds of genetic conditions for a good number of genetic conditions. The larger the area of mutation or deletion, the more severe the condition will be typically. Genetic testing is done in a variety of locations and the turn-around time for the return of results varies on the depth and complexity of the test. Anywhere from a few days to several months is fairly standard though.

7. Why is genetic testing important?
Everyone has a genetic code and many disorders can be traced in part to a genetic basis
Genetic testing can be used to help diagnose existing disorders and also to predict future disorders.
The number of genetic tests available is rapidly approaching 1000, and the number of genetics professionals is also growing (genome.gov)
Genetics can have effects on not just physical health but also mental health and general well-being
When working in a health care field we can see a wide variety of patients with a wide variety of problems. Genetics helps to link everyone together. With the many genetic tests available we can attribute certain disorders to certain mutations/problems. We can even make predictions about future health concerns. Many conditions have both a genetic and environmental basis-by recognizing this a wide variety of professionals from different disciplines can utilize genetic testing to further enhance care in the present and future. The number of genetic professionals is increasing, making it more likely that patients can receive personalized care that addresses all aspects of health. Especially for conditions that affect multiple systems and aspects of life it is important to have a whole team of medical professionals ready to deal with each aspect. (Genetic counselor/doctor, neurologist, dietician, psychiatrist, cardiologist, social worker, etc). For instance, it has been found that there is a genetic basis for certain cases of bipolar disorder. Genetic testing can confirm and provide diagnoses, making it that much easier to plan ahead for future milestones and the team members that will be a part of getting the patient to those milestones.

8. Genetic testing is important for all health care professionals to understand
Primary care physicians
Nurses
Psychologists/psychiatrists
Specialists
Researchers
Genetic doctors, counselors
There are many professionals that are involved in the care of patients and may come in contact with genetics. It often takes time for patients to receive an accurate diagnosis and gain regular care. Primary care physicians like a local doctor are usually the first stop in the search for answers. At the hospital level nurses and specialists are abundant, along with genetic doctors and genetic counselors. All of these individuals are integral to the care of a patient with a genetic condition. Oftentimes, these genetic conditions may also affect aspects of mental health, necessitating that psychologists/psychiatrists get involved. Finally, researchers do a lot of the behind the scenes work when it comes to patients with genetic conditions but they are just as important. Without researchers we wouldn’t even be able to offer the huge array of tests available today or quickly return results to patients. Genetic conditions are often multi-system and can have a huge array of representations. Even patients with the same genetic condition can exhibit vastly different symptoms. When a diagnosis seems unclear and the issue is multi-faceted or simply unknown, consider that there may be a genetic basis at work. Referring to a genetics professional can clear doubts or confirm a diagnosis.

9. Genetic Disorders 22Q11.2 Phenylketonuria Tuberous Sclerosis
Neurofibromatosis
These are just a few of many genetic disorders that have genetic testing available. PKU is tested for in newborn screenings. When an infant is born with PKU the level of a protein called phenylalanine build up in the body, eventually leading to severe intellectual disability. Down syndrome can be detected in prenatal testing and is caused by an extra third chromosome 21. Many of these disorders are detected by diagnostic testing. Neurofibromatosis and tuberous sclerosis both cause benign tumors to grow in the body and are often associated with learning disabilities or ADHD, and unique skin problems. In TS benign tumors often grow in the brain and kidneys. 22Q11.2 is yet another genetic condition that affects many systems of the body.
ALL of these disorders can happen to anyone, anywhere. By being aware of the prevalence of genetic conditions, we can be better prepared to make proper referrals and support potential genetic testing.
Down Syndrome

10. Genetic disorders can be complex and multifaceted
Multisystem
Range of severity
Presence or absence of symptoms
Overlap with many other disorders/problems
Preparation for future struggles
Necessity of increased testing, screening
Genetic conditions are very multifaceted. They can affect many systems in the body (cardiovascular and digestive for example). There is a huge amount of variability in the severity and/or presence of symptoms. Some cases may be very severe and limit normal everyday function while others may be so mild they go undetected for years. Because these conditions are multifaceted they often overlap with other disorders or struggles. For example, many disorders can lead to developmental delays or ADHD symptoms as part of the larger disorder. It can be easy to focus on just one problem, like ADHD, and neglect the fact that there may be an underlying genetic cause for the ADHD and other symptoms that have not presented themselves yet. By having a diagnosis through testing we are able to prepare patients for the future. Many conditions present a unique set of challenges that can be planned for and addressed early. For example, neurofibromatosis can cause high blood pressure, growth of noncancerous tumors and skeletal abnormalities like scoliosis. ADHD and learning disabilities sometimes accompany this as well. By knowing this we can plan ahead for proper care. Many of these genetic disorders also require a higher frequency of routine testing and screening. NF and TS particularly are distinguished by the growth of many tumors that are typically noncancerous but can cause health problems. In TS especially it is necessary to have regular MRIs and kidney ultrasounds to check for tumors and address their growth as early as possible.

11. 22Q11.2 Heart problems Cleft palate Distinct facial features
Immune deficiency
Kidney problems
Seizures
Feeding issues
Hearing loss
Development delay &/or ADHD
Risk of mental illness
22Q11.2 deletion syndrome, also known as velocardiofacial syndrome is a great example of the multifaceted nature of genetic conditions. 22Q is caused by a deletion on one copy of chromosome 22, typically resulting in a loss of about 30 or 40 genes. Listed here are some of the most common symptoms and problems associated with this syndrome. Each patient is unique and often exhibits a huge range of severity. Some cases are so mild they can go undetected for several years. 22Q can be found using fluorescent in situ hybridization (FISH), which is a type of genetic testing. There are several organizations dedicated to 22Q support, including the Dempster Family Foundation.

12. Types of Genetic Testing
Tests can be designed to examine single nucleotide mutations or multiple chromosomal errors
Tests for different circumstances:
determine carrier status
diagnose specific disorder
test prenatally for conditions
screen newborns (e.g. PKU)
determine future risks (predictive/presymptomatic)
test fertilized eggs prior to implantation
forensic investigations
Give background on each type of genetic testing, remember predictive is for person with family history of disorder but no current symptoms. There is a huge array of genetic testing options. Karyotypes (shown to the right) look at the genetic information of a person on the chromosome level while more sensitive tests can look at single nucleotide mutations or all of the genes in a particular segment of DNA.

13. Obstacles
There are many conditions that have yet to be described by genetic testing
Unclear effects of genetics versus environmental cues
Sensitivity rates of some tests
Translating results into treatments
Some conditions are so rare they haven’t been documented or researched. Others are affected by too many genetic areas to be properly attributed (cancer, Alzheimer’s, etc). However, there are quite a few rare genetic disorders that do have testing available-GeneDx is a company that focuses on rare genetic disorder testing, for example. Several disorders are caused by a wide array of factors. While many if not most conditions do have a genetic basis, many are also affected by environmental or outside factors. This can make it difficult to make clear cut diagnoses and justify ordering genetic testing.
Many genetic testing options have a very high fidelity rate. However, some testing is very new or unable to catch mutations below a certain threshold. In these cases, the sensitivity of a genetic test may not be perfect but can still be very good.
Sometimes a diagnosis does not leave a clear path of treatment. Especially for very rare conditions, we may not know how to proceed in treatment beyond providing proper support and regular check-ups/screenings.
These things are constantly changing as new testing, new treatments and better understanding are brought to light.

14. Ethical concerns Informed consent Incidental findings Children
Confidentiality
There are boundaries when it comes to testing though. All testing requires the consent of the patient or the parents if the patient is a minor. This includes an informed consent form with signatures and descriptions of all information that may come out of a particular test. This is especially important in carrier and predictive/presymptomatic testing. These tests provide information about disease and genetics that are often not a problem for the patient yet. This can make it difficult for the patient to accept such testing and results (hence extensive informed consent).
Incidental findings are genetic information about disease (or risk for disease) that can be found while searching for other genetic information. Since these results pertain to disease and health we are often required to share such findings with the patient, along with the results of the testing they ordered. Children present a unique challenge as well because despite their level of maturity, all testing decisions must go through the parents. Also, in terms of genetic diagnoses or risks for disease, results can be especially difficult for a child to handle. Therefore results are returned to the parent only and the parent must decide whether to share those results with the child or not. This brings in many questions of autonomy and right to know your genetic information as a child. Confidentiality is fought for and protected in part by GINA, the Genetic Information Nondiscrimination Act of All sharing of results must be approved by the patient and when DNA is collected for later use it is normally stored with de-identifying data and protected under lock & key.

15. What is genetic counseling?
According to the National Society of Genetic Counselors,
“Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease.”
Genetic counselors often serve to facilitate the return of genetic testing results, along with ordering testing, explaining the tests, obtaining consent, and counseling the patient/family through the process.

16. Genetic counseling consists of:
Assessing medical and family histories to determine risk factors and chance of disease occurrence
Educating about genetic testing, patterns of inheritance, disease management, prevention, research, and resources
Counseling to facilitate informed decisions and help patients cope with the condition
Genetic counselors now have the ability to order genetic testing themselves, rather than forwarding requests to a doctor. Many genetic counselors also participate in the research setting, write letters for insurance coverage, and assist in academic enhancement/support (if tied closely to a genetic counseling graduate program).

17. Genetic counseling profession
NSGC
Networking
Academic advancement
ABGC
Grants accreditation to genetic counselors and genetic counseling graduate programs
Facilitate Certified Genetic Counselor examinations
The NSGC is a professional organization specifically for genetic counselors that promotes networking and the profession in general. There are opportunities for academic advancement as well. The ABGC ,or American Board of Genetic Counseling, is the organization responsible for granting accreditation to all genetic counselors and genetic counseling graduate school programs in the US. They also facilitate the Certified Genetic Counselor examinations that all genetic counseling students must pass to become certified.

18. Job opportunities for genetic counselors
Hospital
Research
Laboratories
Public Health
Pharmaceuticals
Marketing
Prenatal
Pediatrics
Cancer
Specialty clinics
Genetic counselors can work in a variety of settings doing a variety of things. Since genetics itself is expanding, genetic counselors have found their way out of the traditional hospital or laboratory setting and into areas of public health and pharmaceuticals. While the majority of genetic counselors go into clinical care (or research), they can specialize in certain types of disorders or areas of counseling. The 3 biggest clinical care avenues are Prenatal, pediatrics, and cancer genetics, followed by specialty clinics in a multitude of areas. (Brief overview of prenatal, pediatrics, cancer, specialty).

19. Graduate School Preparation
2 year Masters of Genetic Counseling
Any major accepted, biology/genetics or psychology with science prerequisites preferred
32 graduate programs in the US, 3 in Ohio
Exposure to genetic counseling, advocacy experience desired
GRE, 3 letters of recommendation, transcripts, essays/personal statement, applications & fees
Interviews in February/March, acceptance in late April, early May
Programs last for 2 years and include the intervening summer, which is typically reserved for a full time genetic counseling internship. At the end of two years most students will produce a publishable Masters thesis. Many of the science class requirements and recommendations include 1 year biology, 1 year chemistry, semester or more of genetics, cell or molecular biology, statistics, organic chemistry, biochemistry and Anatomy & Physiology. Experience with genetic counseling such as shadowing or internships are recommended but not required, which is the same expectation for advocacy experience like Planned Parenthood or Crisis hotline counseling. Most schools take a comprehensive look at applicants and therefore do not have minimum GRE score requirements. Most applications are due in early January.

20. Recap
Genes have complex and multifaceted impacts on our health and well-being
Genetic testing is an important tool for health professionals and their patients for disease management and planning purposes
Genetic counseling is a growing field that will provide exciting job opportunities for years to come.
Hopefully this presentation has broadened your worldview on genetic testing, genetic conditions, and genetic counselors. As we move into the future we will see more genetic tests become available, which will hopefully translate into better treatments and possible cures. Genetic counselors will be invaluable to this process as they create a bridge between doctors and patients. They have the necessary scientific background but are also in touch with the patients needs and can counsel families through difficult times. You will undoubtedly come in contact with something related to genetics in your lifetime, if you haven’t already. Having some knowledge base will be greatly beneficial as you maneuver your professional careers and work with patients, families and a variety of individuals.

21. Medical-dictionary.thefreedictionary.com
Glossary of Terms
En.wikipedia.org
DNA: deoxyribonucleic acid, double stranded molecule containing all information for cell growth and function
Chromosome: structure containing genetic material (DNA), the DNA strand is wrapped around proteins. Chromosomes occur in pairs.
Gene: the basic unit of heredity, directs the structure of necessary protein(s) and determines phenotype with the environment
Phenotype: physical expression of a gene
Mutation: A change in the genetic code of a gene/chromosome, can be positive or negative
Nucleotide: basic building block of an amino acid, made up of a nitrogenous base (adenine, guanine, thymine, uracil, cytosine), sugar (deoxyribose in DNA) and a phosphate group
Amin0 Acid: structural pieces of a protein coded for by codons (set of 3 nucleotides) and linked together by peptide bonds
Karyotype: depiction of all the chromosomes in a cell, sorted by size, pair, and number

22. Web Site Resources
American Board of Genetic Counseling (
National Society of Genetic Counselors (
Genetics Home Reference (
Dempster Family Foundation (dempsterfamilyfoundation.org/)
Graduate school program websites
Hospital websites
NCBI’s Genetic Testing Registry (
You can find a wealth of information about genetics at these sites and many others. If you have any questions feel free to ask! If you have not gotten a handout with the slides yet please let me know. I hope you have enjoyed this presentation and learned something new. Thank you so much!