Transcript Family Tree DNA - The Adapa Project

WHAT DOES YOUR GENOME SAY ABOUT
YOU? WHO SHOULD KNOW WHAT IT SAYS?
Spring 2016
Original case reated by:
personal genetics education project
Harvard Medical School
Revisions by: AD Johnson, J Curran,Wake Forest University
WAKE
BIOLOGY
Our Genome is Our Personal, Unique
DNA Information
• Affects appearance,
behavior, health
• Half inherited from
each parent, so:
– We share traits with
our parents
– Siblings share traits
– We pass traits to our children
2016: Even identical
twins are unique!
MOST Traits & Variation Are Result Of
Multiple Genes in Genome + Environment
Example:
This black
female lab had
THREE colors
of puppies!
What Genes in Parents Produced These Colors?
• At least SEVEN genes control coat colors
• Each is different part of integrated “system”
One Locus, Called E Locus, Determines If Dogs
(or Any Mammal) Makes Melanin At All
• Encodes
receptor for
melanocyte
stimulating
hormone (MSH)
• No receptor = no
pigment
• How inherited,
& WHY?
Which Dog Is LOW in Melanin?
The B Locus Controls Whether Dogs
Make Black or Brown Melanin
• Melanin is
brown until last
step
• No last enzyme
= brown
• With last
enzyme
Here is a Gene-Environment Interaction
Body Temp Affects a Siamese’ Color Pattern
One cat in show condition
and at home after retiring
A Temperature Sensitive Locus Controls When
Siamese Cats Make ANY Melanins
DOPA oxidase
• Body heat makes
enzyme unfold
– No first enzyme
= pale
• Cool areas make
working enzyme
– With enzyme
= dark
Temp
sensitive
What Is Genotype, Phenotype of Mother, Father
That Produced These Puppies?
Pedigrees Trace Traits in Families Over
Time
What Pattern Do You See?
Dominant Traits Appear Every Generation: One
Copy of Mutated Allele is Enough
Marfan sydrome: affects
aorta, eyes, skeleton,
lungs
1. All affected individuals
have 1 affected parent.
2. About ½ of all children
from an affected parent
are affected.
3. Appears at different
What Pattern Do You See?
These Are Recessive Inheritance Patterns:
TWO Mutant Copies of Allele Needed
Sickle cell anemia: recessive
condition
1. Heterozygotes are “carriers.”
2. Unaffected parents can
produce affected children.
3. About ¼ of children of 2
carriers are affected.
4. All children of affected
individuals carry trait.
5. “Consanguinous” marriages
increase risk
What Can We Deduce From This Pedigree?
What Can We NOT Say?
Maria
Steven
Age 50
breast cancer
Ages 22-37
Vanessa
Emily
Angela
Malcolm
Chris
Ashley
What If We Cannot SEE Differences?
• Coat color, Marfan’s, SCA can be traced
b/c responsible genes create visible changes
• Many disease genes:
– Do not create visible “phenotype”, or
– Appears too late for diagnosis, treatment
• How do we trace important genes we cannot
see?
Which Celebrity’s Genetic Test Made News?
• 2013: double
mastectomy at
37
– 87% risk of
breast cancer
– Multiple family
members died at
young ages
– 50% risk ovarian
cancer
“Reading” Our Genome: Genetic
Marker Tests
• GQ #1: How do we know what to test for?
• GQ #2: What are the potential benefits, limits
to genetic marker tests?
• GQ #3: What do we know as facts? What are
we assuming? What more do we want to
know?
Available Today! Our Entire Genome
• NIH Next-Gen Sequencing Goal:
– “Complete” personal genomes
– 6 Mbp sequenced for ~$1000
• Why 6 Mbp? Why $1000
6Mb Is What Makes Us Different!
• Human genomes are 99.8% identical.
• Total genetic variation is:
0.2% (1/500th) of genome, OR
(3.2 x 109 bp × 0.002) ~ 6 million bp
• So WHY $1000?
“Reading” Our Genome: Whole Genome
Sequencing
• GQ #4: What are potential risks & benefits of knowing
entire genomes?
• GQ #5: Who should have access to the data?
• GQ #6: What information is/should be “public” vs.
“private”?
• GQ #7: What decisions can be made based on those data?
Three Main Types of Genetic Tests
• Clinical tests
– Mandatory:
• State of NC’s newborn screen
– Diagnostic:
• Natera: Panorama Test, Horizon Screen
• Pathway Genomics: Carrier DNA Insight
• Federal identity tests
• Direct to consumer tests
Elective DNA Testing
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Genographic Project
23 and Me
Ancestry DNA
Family Tree DNA
Full Genomes
Determigene
Sure Genomics
• All currently active
companies
• Different:
– Tests
– End goals of testing
– Levels of supporting
evidence
– Data sharing plans
Summarizing a Genetic Test Service
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What are they testing?
Why are they testing it? What is the rationale?
What is the evidence supporting their testing?
Is this a “reasonable” testing tool?
Who has access to the data collected?
Have there been problems with their tests?
Groups Will Report Back on One Company
• Have 5 minutes at start of class to organize
• ~5 minute presentation:
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What is group testing?
Why are they testing it? What is the rationale?
What is the evidence supporting their testing?
Is this a reasonable test?
Who has access to the data collected?
• 2-5 minutes for follow-up questions
Individual Homework: Follow-Up Summary
1. As a class, what were our major findings?
(Limit to max. of 5)
2. What questions did we leave unanswered, or
open for future discussion?
3. What are the greatest risks, benefits of genetic
and genomic testing?
What EVIDENCE are you basing your position on?
Individual Homework: Debrief and Wrap-Up
4. What were our learning goals for this
ENTIRE topic?
5. Which activities helped us get to those goals?
6. Anything we should not do again?
7. What else would have been useful?
Genetic Tests: Comparison Example
State of NC’s newborn screening program
• Mandatory clinical test for all newborns
• Starting Links:
– http://www.babysfirsttest.org/newbornscreening/states/north-carolina
– http://www.ncdhhs.gov/dph/wch/families/newborn
metabolic.htm
Genetic Tests: Comparison Example
Natera Inc., Panorama Test
• Prenatal clinical test through physicians only
• Starting Links:
– http://www.panoramatest.com/en/expecting-mother
– http://www.panoramatest.com/healthcare-provider
TESTING COMPANIES TO EVALUATE
Companies are numbered in order they
will be presented.
Which group evaluates the company
was assigned at random.
Genetic Tests: Class Example #1 Group 2
National Geographic Foundation’s
Genographic Project
• Direct to consumer test / research
• Starting Links:
– https://genographic.nationalgeographic.com
– http://education.nationalgeographic.com/education/gen
ographic-project-educator-discount/?ar_a=1
Genetic Tests: Class Example #2 Group 6
23 and Me, Inc.,
• Direct to consumer tests
• Ancestry screening and health markers
• Starting Links:
– https://www.23andme.com
– https://www.23andme.com/research/
Genetic Tests: Class Example #3 Group 4
Ancestry DNA
• Direct to consumers
• Personal DNA marker testing
• Starting Links:
– http://dna.ancestry.com/
– http://dna.ancestry.com/legal/informedConsent
Genetic Tests: Class Example #4 Group 1
Family Tree DNA
• Direct to consumers
• DNA analysis for lineage tracing
• Starting Links:
– https://www.familytreedna.com/
– https://www.familytreedna.com/learn/
Genetic Tests: Class Example #5 Group 7
Full Genomes Corp.
• Direct to consumer test
• Full genome sequencing
• Starting Links:
– https://www.fullgenomes.com
– https://www.fullgenomes.com/purchases/11/
Genetic Tests: Class Example #6 Group 5
Determigene
• Direct to consumer
• Multiple DNA tests
• Starting Links:
– http://www.determigene.com/
– http://www.determigene.com/products_services.asp
Genetic Tests: Class Example #7 Group 3
Sure Genomics, Inc.
• Direct to consumers
• Full genomic DNA sequences
• Starting Links:
– http://www.suregenomics.com/
– http://www.suregenomics.com/about-us/