1. Family History Healthcare Personalized for You:
Understanding Genomics and Precision Medicine
OLLI Spring 2017

2. Happy DNA Day!

3. Happy DNA Day!

4. James Watson and Francis Crick April 25, 1953
Article in journal Nature: "we would like to suggest a structure for the molecule deoxyribonucleic acid-DNA

6. Genetic Testing

7. Genetic Tests: What They Can Tell You
Genetic tests analyze your DNA by looking at different areas of your genome
Some tests analyze SNPs
Some tests analyze a specific region of your DNA—a gene
Some tests look at only the protein coding regions (exons)
Some analyze your entire genome

8. Genetic tests: GWAS Genome Wide Association Study
GWAS tests analyze a set of SNPs across the genome
Single Nucleotide = a single A, G, T, or C
Polymorphism = fancy word for common variation
There are about 10 million common SNPs in the genome
SNPs are often grouped and inherited together
What does GWAS tell you?
GWAS tests determine what is the SNP association with different diseases by quickly scanning the entire genome for common variations (via SNPs)
In genetics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an examination of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait.

9. Genetic Tests: WES and WGS
WES or Whole Exome Sequencing provides a sequence of the As Cs Ts and Gs of the exons (protein coding areas)
WGS or Whole Genome Sequencing provides a sequence of the As Cs Ts and Gs of exons, introns and other non-coding areas of the genome
Unlike the names imply, these are imperfect tests!
There are still some limitations to the technology
Certain areas are not ‘picked up’
Interpretation of variants is limited
What do WES/WGS tell you?
WES/WGS used mostly to diagnose rare and severe genetic conditions
Often to help diagnose a “mystery” disease

10. Genetic Tests: Screening Tests
Tests that identify a subset of a populations at risk for a condition or a disease
Newborn screening
Carrier screening
Maternal screening during pregnancy: carrier testing, serum testing, chromosome testing
Adult screening for various diseases may be the norm in the future
BRCA, colon cancer, hemochromatosis, alpha-1-antitrypsin deficiency
Discussion of these currently underway in the medical community
Newborn screening – most states screen for 34 conditions (as recommended by March of Dimes) but it varies state to state, blood based (heel prick), most look at levels of certain analytes in the blood rather than DNA sequence
Carrier screening – population dependent: diseases more common in Jewish population, CF, Sickle Cell, spinal muscular atrophy. Some DTC tests like 23andMe include carrier screening for some conditions (currently list of 41 conditions, as of 4/14/17), look at DNA sequence
Maternal screening – use maternal blood to measure certain analytes and ultrasound to detect chromosomal disorders like Down syndrome or neural tube defects. Some tests look at fetal DNA circulating in mother’s blood stream

11. Other Genetic Tests Ancestry testing
Offered by 23andMe, Ancestry, Family Tree DNA and MyHeritage
SNPs analyzed to predict haplogroup - geographical estimate of where your ancestors were from
SNPs analyzed to identify common segments of DNA shared by individuals
Can identify relatives, confirm or deny relationships

12. Test Interpretation
Many testing companies do the interpretation for you
Promethease and Interpretome
Do not test for disease genes
Report SNPs from SNPedia that are associated with diseases according to published research and clinical studies
Genetic testing by a clinical laboratory may be necessary to confirm a disease association

13. Testing Costs Test dependent
For disease testing, insurance will usually cover the cost
For personal use, you’ll pay out of pocket
Ancestry testing = $79 - $99
Health + Ancestry = $199
Only SNP Interpretation = $5
Whole Genome Sequencing + Interpretation = over $1000

14. Summary: Genetic/Genomic Tests
Genetic Genealogy tests: analyze thousands of SNPs
Most companies choose SNPs NOT associated with genes/health/disease
GWAS: analyze thousands to millions of SNPs to look for association with disease
WES: analyzes the protein coding regions (exons) ONLY
WGS: analyzes the exons, introns and other non-coding areas of the genome—the Whole Genome

15. Questions?

16. What free ‘Genetic Test’ do you have available right now?

17. Family History!

18. There are many ways to document a family history as well as a family HEALTH history

19. Your “free” genetic test
Family Health History
"Single most important source of information about your future health and risk of illness"
A free “window into your genome”

20. Family Health History: Why is it important?
Having a first degree relative with a disease can increase your risk for the same disease 2 or 3 fold
First degree relative = parent, sibling or child
Having two first degree relatives with the same disease can increase your risk 5 fold
Similar risks are found if you have other relatives with the same disease

21. Other important points:
Family members share some of the same genetic information--their genomes are very much alike
Often family members share similar environments
Family Health History has its limitations
People develop diseases without a family history of the disease
Adoptees often lack any family health information, but this is changing slowly

22. How Well Did You Do Collecting Your Family Health History Information?

23. Family Health History: Red Flags
Several closely related individuals affected with the same condition or system/organs involved (heart, kidney, lungs)
Sudden cardiac death in a person who seemed healthy
Bilateral disease in paired organs (eyes, kidneys, lungs, breasts)
Early onset of disease that usually affect older individuals
Diseases occurring in opposite gender typically affected (ie male with breast cancer)
Medical problems in the offspring of parents who are related (consanguineous)
Multiple common disorders in related individuals, especially if occurring at an earlier age of onset than is typical

24. What to do with Red Flags
Make note of "red flags"
Discuss with your healthcare provider to address any concerns
Consider referral to genetic counselor
No red flags! Great! Be sure to regularly update your family history

25. You have your Family Health History…Now what?

26. Documentation of Your Family Health History
Record anyway you like but:
There is a tool to standardize the information obtained: pedigree
First used in 1800's to record a family history of color blindness
Pedigree standards first published in 1995, adopted in 2008

27. Standard Pedigree
Quick and accurate record for yourself and healthcare provider
Circles are females, squares are male
Vertical and horizontal lines represent relationships
Shading, symbols document health issues/diseases
Also records ethnicity, consanguinity, and adoption

28. Standard symbols

29. Constructing a pedigree
Draw by hand
You can use the web tool mentioned in the book
Privacy protected
Pedigree can be integrated into electronic medical/health records, printed, shared with family members

30. Example

31. Risk Assessment http://familyhistory.hhs.gov
The Pedigree tool identifies diseases you or a relative may be at increased risk to develop
Asks questions about lifestyle, habits, weight, height, environmental influences
Answer them by checking off boxes
Provides a risk figure for developing the disease

32. Questions?

33. For Next Week! What diseases to add?
In the next weeks we are prepared to discuss some single gene diseases that are more common in certain ethnic groups
We also will discuss genomes and diabetes, heart disease, aging, infectious diseases, mental health disorders
Genomes and medicines
Based on your family histories are there other diseases you would like to know about?
Let us know via or the website comment box