Introduction to Genetics and Public Health
Heather Creswick, M.S.
John Quillin Ph.D.

Is genetics relevant for you? You might be surprised. Listen to this podcast and find out as well as this one from Dr. Francis Collins (Click here for audio link).

Objectives:
After reviewing these materials, you will be able to:

• Explain, in broad terms, genetics and genomics and how they relate to the essential functions of public health.
• Describe three concrete examples (case studies) of how genetics can be applied to public health.
• Improve your self-assessed public health competency vis-à-vis public health workforce recommendations from the CDC.

Learning Outline:

1. Pre-session self-assessment
2. Introduction to genetics and genomics
3. Relevance of genetics/genomics to the essential functions of public health
4. On-the-job application of public health genomics
5. Post-session self-assessment

Pre-Session Self-Assessment
How prepared are you to use the power of genomics in the work of public health? Fill out the Self-Assessment before going to the next section.If you are using Windows 10 you will need to be sure to right click and open the file in a PDF reader.
Next, work through this self-paced Introductions to Genetics. This site has changed since the spring. Please review the second and third options, what are DNA and genes? And what is inheritance.?
The term “genetics” typically refers to the study of single genes. New technology now allows relatively quick and increasingly cheaper analysis of multiple genes, even a look at all ~21,000 genes. The study of all of a person’s genetic information, in aggregate, is called “genomics”. Read this overview of genomics from Healthy People 2020 and how it relates to two HP2020 objectives.
Below are some key words and concepts to help you form a knowledge base for public health genomics.
Key Words

• Autosomal dominant– genes that exhibit their effects when only one altered copy is present (e.g. neurofibromatosis, Huntington disease, many cancer susceptibility genes like BRCA1/2)
• Autosomal recessive – genes that exhibit their effects when two altered copies are present (e.g. sickle cell anemia, cystic fibrosis)
• Birth defect – any morphological abnormality present at birth (e.g. cleft palate, neural tube defect)
• Cancer cluster – a greater-than-expected number of cancer cases that occurs within a group of people in a geographic area over a period of time
• Children with special health care needs – includes all children who have or are at risk for chronic physical, developmental, behavioral, or emotional conditions and who also require health and related services of a type or amount beyond that required by children generally.  It is estimated that 18 million children in the United States have these special health care needs (Maternal and Child Health Bureau)
• Congenital anomaly – a defect that is present at birth (considered synonymous to “birth defect”)
• Genetic susceptibility – a tendency to a disease or health alteration based on genetic changes
• Genetics - the scientific study of heredity, how particular qualities or traits are transmitted from parents to offspring. We have data on about 21,000 human genes
• Genomics – the study of all of a person’s genes and their function, in aggregate
• Lynch Syndrome – the most common form of hereditary colon cancer, inherited in an autosomal dominant manner. About 2% of colon cancers are associated with Lynch Syndrome.
• Human Genome Project – the 13-year (1990-2003) federal project to map the total human DNA sequence of ~21,000 genes
• Microsatellite instability – within an individual, variation in the lengths of repeated sections of DNA; often a sign that someone’s DNA repair mechanisms are not working properly; commonly found in colon and endometrial cancers associated with Lynch Syndrome
• Multifactorial – caused by a combination of genetic and environmental factors
• Next-generation sequencing (NGS)  - a method for determining the genetic code (order of DNA nucleotides); NGS breaks a patients genome into millions of copies of fragments of DNA and then aligns them with a reference genetic code. Differences in the alignment indicate a mutation or some variant sequence.
• Polymorphism – DNA variation that is not yet known to have clinical significance; polymorphisms are common, sometimes defined as occurring with a frequency of at least 1% in the population
• Severe Combined Immune Deficiency (SCID) – an X-linked recessive hereditary disorder of the immune system, typically associated with mutations in the IL2RG gene
• X-linked Recessive Inheritance – A familial inheritance pattern resulting from a mutation in a gene on the X chromosome. In X-linked recessive conditions, individuals with a normal X chromosome typically will not have the disorder. Female carriers with one normal X chromosome and one X chromosome with a mutation may not have the disorder. Males, however, have only one X chromosome, so if they have inherited the gene mutation they will have the disorder.

Concepts:

• It is estimated that influences on health and disease are 40% behavioral, 30% genetic, 20% environmental, and 10% health care.
• The human body contains ~21,000 genes typically packaged for cell division in 46 chromosomes (23 chromsome pairs).
• Genes help determine our responsiveness to environmental changes.  Genes also interact with one another. 
• The causes of birth defects include chromosomal alterations, DNA changes, teratogens, and multifactorial conditions.
• 3-4% of children are born with a birth defect.
• About 240,000 children in Virginia are estimated to have special health care needs. 
• The burden of disease and developmental/intellectual disabilities may be reduced through genetic understanding and services.
• Family history is increasingly being valued as a public health tool to screen for common diseases.
• “We are all diseased, just not diagnosed yet.” Francis Collins MD PhD, Medical Geneticist, former Director, National Institute for Human Genome Research, now NIH director

The following web sites may be useful for your further study.

• Office of Public Health Genomics
• Genetic Alliance
• Genetics Home Reference
• Lynch Syndrome Screening Network
• March of Dimes
• National Human Genome Research Institute
• National Coalition for Health Professional Education in Genetics
• Online Mendelian Inheritance in Man
• U.S. Surgeon General's Family History Initiative
• NIH State-of-the-Science Conference: Family History and Improving Health

Also, scan the following:

• Zettler PJ, Sherkow JS, Greely HT. 23andMe, the Food and Drug Administration, and the future of genetic testing. JAMA Internal Medicine 2014;174(4): 493-494.
• Genomics & Primary Care  (Also applicable to the session on aging.)
• Wang L, McLeod HL, Weinshilboum RM. Genomics and drug response. New England Journal of Medicine 2011;364:1144-1153.

Relevance to the Essential Functions of Public Health
Throughout your training in public health, you will learn about the 10 Essential Public Health Services:

1. Monitor health status to identify and solve community health problems.
2. Diagnose and investigate health problems and health hazards in the community.
3. Inform, educate, and empower people about health issues.
4. Mobilize community partnerships and action to identify and solve health problems.
5. Develop policies and plans that support individual and community health efforts.
6. Enforce laws and regulations that protect health and ensure safety.
7. Link people to needed personal health services and assure the provision of health care when otherwise unavailable.
8. Assure competent public and personal health care workforce.
9. Evaluate effectiveness, accessibility, and quality of personal and population-based health services.
10. Research for new insights and innovative solutions to health problems.

An ongoing challenge for public health personnel is to incorporate current understanding of the science of health and disease in effective and ethical public health measures.  Your understanding of the relevance of the genetic components of your family health history to your own health, and your willingness to think about these complex issues for society and public health are both part of your legacy.  Think genetically.

Review the CDC Genomic Workforce Competencies and continue to reflect upon them as you go through your MPH program (focus on the first two and 5th bullets).

The following have been identified as public health functions relevant to genetics:

• public health assessment
• evaluation of genetic testing
• development, implementation, and evaluation of population interventions; and
• communication and information dissemination. 

Critical issues include:

• partnerships and coordination
• ethical, legal and social issues; and
• education and training.

[See also: Genetics and Public Health in the 21st Century (Muin Khoury, Wylie Burke, Elizabeth J Thomson (eds.), New York, Oxford University Press, 2000) is a comprehensive monograph about using genetic information to improve health and human disease.]

On-the-Job Application of Public Health Genomics
Imagine you have graduated with your MPH. It is your first week as Director of Public Health Genetics for Virginia. This class is going to walk you through three public health genetic issues that arrive on your desk that first week. How will you handle them?
(Each of the PowerPoint presentations below includes audio of the lecturers guiding you through each slide. Make sure you are at a computer at which you can listen to this audio. You will need to manually advance each PowerPoint slide.)

Day #1 as Director of Public Health Genetics
Genetics Competency Elements:

• Identify ethical and medical limitations to genetic testing, including uses that don’t benefit the individual.
• Participate in strategic policy planning and development related to genetic testing or genomic programs.
• Participate in the evaluation of program effectiveness, accessibility, cost benefit, cost effectiveness and quality of personal and population-based genomic services in public health.
• Maintain up-to-date knowledge on the development of genetic advances and technologies relevant to his/her specialty or field of expertise and learn the uses of genomics as a tool for achieving public health goals related to his/her field or area of practice.

You receive these reports on your desk:

• The first describes the possibility of expanding the state’s newborn screening panel to include Severe Combined Immunodeficiency Disorder (SCID)
• The second shows a shortage of genetics health professionals who have training to care for infants identified with a disorder on newborn screen.

What other information do you want?
Where are the gaps?
What actions do you recommend?

NewBorn Screening PowerPoint
 
Some additional background:
1) MMWR Sept. 19 2008:Impact of Expanded Newborn Screening — United States, 2006
2) National Birth Defect Prevention Network
3) National Newborn Screening and Genetics Resource Center
4) Virginia Department of Health Newborn Screening Program

Late Breaking June 8 JAMA, PH Research and use of stored dried blood spots,discusses the potential problems of research using stored samples from past newborn blood screens..

• Maintain up-to-date knowledge on the development of genetic advances and technologies relevant to his/her specialty or field of expertise and learn the uses of genomics as a tool for achieving public health goals related to his/her field or area of practice 
• Collaborate with existing and emerging health agencies and organizations, academic, research, private and commercial enterprises, including genomic-related businesses, agencies and organizations and community partnerships to identify and solve genomic-related problems
• Identify ethical and medical limitations to genetic testing, including uses that don't benefit the individual 
• Participate in strategic policy planning and development related to genetic testing or genomic programs

Your Congresswoman has two grandchildren with autism spectrum disorder and included a promise to “to do more testing for autism” in her campaign.  She has representatives of a company that has a panel of markers for autism asking to schedule a meeting with you so that you can become her state professional advocate to add this testing to the newborn screen.

What other information do you want?
Where are the gaps?
What actions do you recommend?
Autism PowePoint

Web-Based Autism Exercise:
Your 18-month-old nephew for whom you sometimes babysit is not talking yet. The bus you take downtown has a sign on it that reads – “Act early. Know the signs. 1 in 160 children has autism.” 50-70% of individuals with autism have a cognitive or intellectual disability. You decide you need to learn more about autism and intellectual (cognitive) disabilities, formerly – and sometimes still called – mental retardation.
Surf the internet or use other resources to answer the following questions.

Question 1. How is autism currently defined?
We see what we know. You need to develop your skills at diagnosis and have standardized methods/tools for screening and identifying conditions. You understand that we often do screening tests as a first step in assessing a potential medical condition (e.g. one blood pressure measurement does not diagnose hypertension).

Question 2. Find the current American Academy of Pediatrics recommended algorithm for screening for autism (sometimes called autism spectrum disorder (ASD) to include children who may not quite meet the narrow definition but who have many of the features).
You learn that having a sibling with autism, and a parent/caregiver/or pediatricians’ concern about the child’s development merit use of a specific autism screening tool and potentially referral for further evaluation and diagnosis.

Question 3. How would you contact the Child Development Clinic at VCUHS?
The diagnosis of ASD is confirmed at this clinic with the ADOS (Autism Diagnostic Observation Schedule) instrument. You understand that autism may be seen in some single gene disorders, untreated metabolic conditions (e.g. PKU), some teratogenic conditions, some chromosome conditions, as well as having multiple genes contributing.

Question 4. Can you find a recent Genome Wide Association Study (GWAS) that described possible genetic contributions to the autism phenotype?
A Genome Wide Association Study is a study that compares the complete DNA of people with a disease or condition to the DNA of people without the disease or condition. These studies help find the genes involved in a disease, and may help prevent, diagnose, or treat the disease. A GWAS typically compares SNPs (single nucleotide polymorphisms) between a large number of well-defined “cases” of the condition and a large number of controls. The strength of the evidence for a true association between a SNP (and nearby nucleotides) and the condition/phenotype depends on the likely number of true associations and the study’s power (sample size and effect sizes) to detect them.

Question 5. How would you find out more about research studies on new treatments?
Some other questions for your consideration:

1. How many children on average are born annually with this condition in Virginia and in the United States?
2. How is the condition treated?
3. What are the issues involved in informed consent/dissent for newborn screening?
4. What needs to be in place for an effective newborn screening and follow-up system for this condition in Virginia?
5. Should autism susceptibility testing be added to the newborn screen?

Day #3 as Director of Public Health Genetics
Genetics Competency Elements:

• Apply the basic public health sciences, (including behavioral and social sciences, biostatistics, epidemiology, informatics, environmental health) to genomic issues and studies and genetic testing, using the genomic vocabulary to attain the goal of disease prevention 
• Identify the role of cultural, social, behavioral, environmental and genetic factors in development of disease, disease prevention, and health promoting behaviors; and their impact on medical service organization and delivery of services to maximize wellness and prevent disease 
• Participate in the evaluation of program effectiveness, accessibility, cost benefit, cost effectiveness and quality of personal and population-based genomic services in public health 
• Develop protocols to ensure informed consent and human subject protection in research and human subject protection in research

When you get to your office this morning, you see that someone has left a copy of HP2020 on your desk, opened to the page describing the new Genomics objectives. The following objective is highlighted: Increase the proportion of persons with newly diagnosed colorectal cancer who receive genetic testing to identify Lynch syndrome (or familial colorectal cancer syndromes). Attached is a post-it note: “What are we going to do about this? Can the Virginia Cancer Registry help?”

See also this JAMA Viewpoin on Family History

What other information do you want?
Where are the gaps?
What actions do you recommend?
PowerPoint on Colorectal Cancer
Some additional background:
Explore these web sites

• CDC National Center for Environmental Health (Cancer Clusters)
• CDC Genetics update by state
• National Cancer Institute
• Virginia Department Cancer Registry
  Post-Session Self-Assessment Be sure to open in a PDF reader and not in Windows if using Windows 10.
  Now that you have reviewed the class materials, are you more competent to incorporate genomics into your public health practice? Did your score on the "self-assessment" improve?