petros tsipouras

1. REMOTE DELIVERY OF GENOMIC
INFORMATION & GENETIC
COUNSELING:
A NEW DISCIPLINE IN
TELEMEDICINE?
SHRIKANT MANE, PHD
DIRECTOR, YALE CENTER FOR GENOME
ANALYSIS
PETROS TSIPOURAS, MD
DEPARTMENT OF GENETICS
YALE UNIVERSITY

2. GENETIC DIAGNOSIS BY WHOLE
EXOME CAPTURE AND MASSIVELY
PARALLEL DNA SEQUENCING:
CHOI ET AL. PNAS: 2009
First report on making a clinical diagnosis using, whole exome capture
and next-generation high throughput DNA sequencing
• 5 month child
presented with failure
to thrive & dehydration
• Treatments for kidney
disease failed
STAS Cl/HCO3
exchanger
• DNA samples were collected and prepared for sequencing
• Identified homozygous missense D652N mutation at a position in
SLC26A3 gene that is known to be associated with congenital chloride
diarrheas.

3. YALE CENTER FOR GENOME ANALYSIS
3
Established in January 2010
11 Illumina HiSeqs, Pacific Biosciences, PGM and Ion Proton
Dell Cluster with 200 nodes/2500 cores and 3 Petabytes storage
25 Full time staff ( 7 PhDs, 2 MDs, 5 with MS degrees)

4. Select publications resulting from Next-Generation Sequencing at
YCGA
Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Bilguvar and
Gunel
Nature, v467, 2010
A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity. Cifuentes
and Giraldez
Science, v328, 2010
Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Choate K Science, v330, 2010
Transcriptomic analysis of avian digits reveals conserved and derived digit identities in birds. Wang et al Nature, v477, 2011
Transposom-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in
mammals. Lynch and Wagner
Nature, Genet. v43, 2011
+
K
channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Choi M Science, v331, 2011
Recessive LAMC3 mutations cause malformations of occipital cortical development. Barak and Gunel. Nat Genet., V43, 2011
Spatio-temporal transcriptome of the human brain. Kang and Sestan Nature, v478, 2011
Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Modi and Girardi Science, v335, 2012
Mutations in kelch-like 3 and cullin 3 causes hypertension and electrolyte abnormalities. Boyden et al Nature, v482, 2012
De novo point mutations, revealed by whole-exome sequencing, are strongly associated with Autism Spectrum
Nature, v485, 2012
Disorders. Sanders and State
Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Krauthammer Nat Genet., V44, 2012
Genomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO. Clark and
Science, v339, 2013
Gunel
De novo mutations in histone-modifying genes in congenital heart disease. Zaidi and Lifton Nature, v498, 2013
Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Lemaire and Lifton Nat Genet., V45, 2013
Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary
aldosteronism. Scholl and Lifton
Nat Genet., V45, 2013
The evolution of lineage-specific regulatory activities in the human embryonic limb. Cotney and Noonan Cell, v154, 2013
Mutations in DSTYK and dominant urinary tract malformations. Sanna-Cherchi and Gharavi N Eng J Med., 2013
Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Lee and
Nature, 2013
Giraldez
Co-expression networks implicate human mid-fetal deep cortical projection neurons in the pathogenesis of
autism. Willsey and State
Cell, 2013 (In press)

5. CLINICAL USES OF GENOME
SEQUENCING
Cancer: sequence tumors to guide initial Rx and Rx of recurrent disease
Inherited susceptibilities
Solve clinical mysteries
Newborn screening?
Genome sequencing at birth?
YCGA is carrying out clinical diagnostic work in collaboration with Dr. Allen Bale
Over 700 exomes are analyzed for various disorders

6. GENETIC TESTING: COUNSELORS
WIDELY NEEDED
2014 marks the first time when demand for genetic counselors outstripped supply in the
United States. The quick spread of genetic testing is accelerating this need and creating
pressure for scalable solutions.
6

7. WHAT IS GENETIC COUNSELING?
“Genetic counseling is the process of helping people
understand and adapt to the medical, psychological,
and familial implications of genetic contribution to
disease. This process integrates the following:
Interpretation of family and medical histories to assess
the chance of disease occurrence or recurrence.
Education about inheritance, testing, management,
prevention, resources and research. Counseling to
promote informed choices and adaptation to the risk or
condition.”
National Society of Genetic Counselors’ Definition Task Force
J. Genet Couns 2006,15, 77-83
7

8. CURRENT EXAMPLES OF REMOTE GENETIC
COUNSELING
Phone counseling sessions
8
Video counseling sessions
Strand remote counseling and sample collection room
at the Mazumdar Shaw Medical Center

9. BUILDING A SCALABLE SOLUTION
Research on the use of an interactive computer program prior to
genetic counseling showed the combination to be more effective than
standard genetic counseling for increasing knowledge of genetic
testing
Resulted in significantly shorter counseling sessions
Shifted the focus of counseling session away from basic
education toward personal risk and decision-making
9
Green, M. J., Peterson, S. K., Baker, M. W., Harper, G. R., Friedman, L. C., Rubinstein, W.S., & Mauger, D.
T. (2004). Effect of a computer-based decision aid on knowledge, perceptions, and intentions about genetic
testing for breast cancer susceptibility. Journal of the American Medical Association, 292(4), 442-452.

10. ENHANCING COUNSELING EFFICIENCY
10
Consenting
Counseling
Session
Family History
Communicatin
g Next Steps
Setting
Expectations
Interpreting
Results
Prime areas for
technological
disruption short-term
Future automation
goal

11. BUILDING A COMPREHENSIVE
SOLUTION
11
Physician
refers
patient to
platform
and
authorizes
lab to
process
sample
Patient
gains
access to
tracking
information,
educational
materials
and
counseling
tools
Lab
processes
sample and
updates its
progress to
all
stakeholder
s
Genetic
Report is
generated
and sent to
physician,
who
engages
counselor
for patient
Genetic
Counselor
can access
patient
information
and focus
session on
dynamic
decision-making
process

12. BUILDING A ROBUST SOLUTION
Physician
Links patient medical
information
Refers the patient into
portal
Can connect directly
to lab and counselors
Receives genetic
report
Can access continuing
education materials
12

13. BUILDING A ROBUST SOLUTION
13
Patient
Creates personal profile
and family history
Can access personalized
educational materials
Makes expectations
explicit and signs consents
Access to scheduling tools
Connects with a genetic
counselor

14. BUILDING A ROBUST SOLUTION
14
Genetic
Counselor
Reviews patient information,
family history and lab report
Works with physician on
patient plan
Engages patient on what
the information means
Provides guidance on
appropriate next steps
Share and access database
of best practices

15. DEVELOPMENT PLAN
15
Technology
Infrastructure
Content
Development
Logistics
Management
User Testing

16. PLATFORM BENEFITS
Technology can be licensed
and used by multiple
stakeholders
Library of content forms basis
of sustainable competitive
advantage
Network effects create
incentives for continued use by
physicians and patients
16

17. THE FUTURE
Complete automation through an intelligent system
17
Physician
refers
patient to
platform
and
authorizes
lab to
process
sample
Patient
gains
access to
tracking
information,
educational
materials
and
counseling
tools
Lab
processes
sample and
updates its
progress to
all
stakeholder
s
Genetic
Report is
generated
and sent to
physician,
who
releases
information
to patients
in online
system
Sophisticate
d and
robust
algorithms
guide the
patients
through
results and
actionable
next steps

18. PARTNERS/COLLABORATORS
Krishnan Ganapathy, MD
18
Petros Tsipouras, MD
Shrikant Mane, PhD
Michael Krauthammer, MD, PhD
Paddaiah Gangisetti, PhD
Elissa Levin, MS
Eric Schadt, PhD
Vijay Chandru, PhD
Priscila Bala, MBA