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Posts Tagged ‘Baylor College of Medicine’

Copy Number Variants (CNV) Alleles to be Detected by a Complete Recessive Carrier Screening Diagnostics

Posted in Chemical Genetics, Computational Biology/Systems and Bioinformatics, Genome Biology, Genomic Testing: Methodology for Diagnosis, Personalized and Precision Medicine & Genomic Research, Population Health Management, Genetics & Pharmaceutical, tagged , , , , , on June 12, 2013| Leave a Comment »

Copy Number Variants (CNV) Alleles to be Detected by a Complete Recessive Carrier Screening Diagnostics

Reporter: Aviva Lev-Ari, PhD, RN

 

Using array comparative genomic hybridization data for 21,470 individuals, Baylor College of Medicine‘s James Lupski and colleagues considered the frequency with which deletions or other disruptive copy number variants appear in genes known for roles in recessive disease. As they report in Genome Research, the investigators unearthed more than 3,200 instances in which deletions affected one allele of a recessive disease gene, affecting 419 different recessive disease genes in all. The CNVs — which render individuals potential carriers of recessive disease — tended to occur in long genes and genes falling far from those contributing to dominant disease risk, study authors note. Based on their findings, they argue that “a complete recessive carrier screening method or diagnostic test should detect CNV alleles.”

Deletions of recessive disease genes: CNV contribution to carrier states and disease-causing alleles

Abstract

Over 1,200 recessive disease genes have been described in humans. The prevalence, allelic architecture, and per-genome load of pathogenic alleles in these genes remain to be fully elucidated, as does the contribution of DNA copy-number variants (CNVs) to carrier status and recessive disease. We mined CNV data from 21,470 individuals obtained by array comparative genomic hybridization in a clinical diagnostic setting to identify deletions encompassing or disrupting recessive disease genes. We identified 3,212 heterozygous potential carrier deletions affecting 419 unique recessive disease genes. Deletion frequency of these genes ranged from one occurrence to 1.5%. When compared with recessive disease genes never deleted in our cohort, the 419 recessive disease genes affected by at least one carrier deletion were longer and were located farther from known dominant disease genes, suggesting that the formation and/or prevalence of carrier CNVs may be affected by both local and adjacent genomic features and by selection. Some subjects had multiple carrier CNVs (307 subjects) and/or carrier deletions encompassing more than one recessive disease gene (206 deletions). Heterozygous deletions spanning multiple recessive disease genes may confer carrier status for multiple single-gene disorders, for complex syndromes resulting from the combination of two or more recessive conditions, or may potentially cause clinical phenotypes due to a multiply heterozygous state. In addition to carrier mutations, we identified homozygous and hemizygous deletions potentially causative for recessive disease. We provide further evidence that CNVs contribute to the allelic architecture of both carrier and recessive disease-causing mutations. Thus, a complete recessive carrier screening method or diagnostic test should detect CNV alleles.

  • Received February 7, 2013.
  • Accepted May 6, 2013.

© 2013, Published by Cold Spring Harbor Laboratory Press

 

Read Full Post »

Inaugural Genomics in Medicine – The Conference Program, 2/11-12/2013, San Francisco, CA

Posted in Genome Biology, tagged , , , , , on February 4, 2013| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

Inaugural Genomics in Medicine

Individualized Care for Improved Outcomes

February 11-12

Moscone North Convention Center • San Francisco, CA

Organized by

Cambridge Healthtech Institute

Monday, February 11

7:30 am Registration and Morning Coffee

8:25 Chairperson’s Opening Remarks

Screening for Rare and

Difficult to Diagnose Diseases

8:30 KEYNOTE PRESENTATION:

Genomically-Supported Diagnostic and

Drug Reposition Strategies out

of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center for Applied

Genomics, Children’s Hospital of Philadelphia

This talk will discuss genomic strategies applied in academia

to identify subsets of patients who, based on their genetic

make-up, are predicted to have a favorable response profile to

drugs that come from reposition opportunities.

9:00 Evolving Approaches to Mutation Detection in

Rare Diseases

Tom Scholl, Vice President, Research & Development,

Integrated Genetics, LabCorp

Emerging trends in this field that include the expansion of

content in clinical tests to include many loci and increased

clinical sensitivity by expanding numbers of mutations detected

or whole gene sequencing will be presented.

9:30 From Raw Sequencing Data to

Functional Interpretation

Daniel MacArthur, Ph.D., Group Leader, Analytic and

Translational Genetics Unit, Massachusetts General Hospital

This presentation will discuss the key lessons learned

from large-scale sequencing studies in both common and

rare diseases with a particular focus on finding mutations

underlying severe muscle diseases.

10:00 Coffee Break with Exhibit and Poster Viewing

10:30 Providing Whole Genome Sequencing in the Clinic

David Dimmock, M.D., Assistant Professor, Pediatrics,

Medical College of Wisconsin

This presentation will focus on advances in the implementation

of genome wide sequencing in clinical practice. It will address

counseling and consent issues specific to testing children.

Specifically, it will highlight the challenges of execution in the

acute care setting.

11:00 Clinical Utility of Whole Exome Sequencing

Christine M. Eng, M.D., Professor, Department of Molecular

and Human Genetics, Baylor College of Medicine

This presentation will discuss the role of whole exome

sequencing in the diagnostic evaluation of patients with

challenging phenotypes of genetic etiology. Examples of

clinical utility, directed medical care, and cost-effectiveness

of the whole exome approach to clinical diagnostics will be

presented.

11:30 A Neuronal Carnitine Deficiency Hypothesis

for Autism

Arthur L. Beaudet, M.D., Henry and Emma Meyer Professor

and Chair, Department of Molecular and Human Genetics,

Baylor College of Medicine

We have published a paper entitled “A common X-linked

inborn error of carnitine biosynthesis may be a risk factor for

nondysmorphic autism” (PMID: 22566635). We propose a

neuronal carnitine deficiency hypothesis as one risk factor

or cause for autism whereby 10-20% of autism might

be preventable.

12:00 pm Luncheon Presentation

(Sponsorship Opportunity Available) or Lunch on

Your Own

Predictive Tests for

Improved Patient Outcomes

1:25 Chairperson’s Remarks

1:30 Implementation of Personalized Healthcare into

Clinical Practice: Lessons Learned

Kathryn Teng, M.D., FACP, Director, Center for Personalized

Healthcare, Cleveland Clinic

Integrating a pharmacogenetics program into clinical practice

requires a vision for the future of healthcare and a roadmap to

reach that vision. Pioneering the road to achieving this vision

has brought challenges and has allowed for the creation of

solutions that might be applied universally.

2:00 Molecular Profiling of Tumors to Select Therapy

in Patients with Advanced Refractory Tumors

Ramesh Ramanathan, M.D., Medical Director, The Virginia

G. Piper Cancer Center Clinical Trials

This presentation will discuss molecular profiling of tumors

using IHC, CGH and whole genome/exome sequencing of

tumors to find actionable targets for therapy. Clinical trials

and case reports of patients treated by this approach will

be presented.

2:30 Sponsored Presentations (Opportunities Available)

3:00 Refreshment Break with Exhibit and

Poster Viewing

3:30 Gene Panels vs. Whole Exome Sequencing in

Cancer Molecular Testing

Madhuri Hegde, Ph.D., FACMG, Associate Professor, Senior

Director, Emory Genetics Laboratory, Department of Human

Genetics, Emory University School of Medicine

TriConference.com 5

Individualized Care for Improved Outcomes

4:00 Next Generation Sequencing and

Cancer Diagnostics

Phil Stephens, Ph.D., Vice President, Cancer Genomics,

Foundation Medicine

Foundation Medicine has developed FoundationOne™, a

CLIA-certified, comprehensive cancer genomic test that

analyzes routine clinical specimens for somatic alterations in

189 relevant cancer genes. Experience with the initial 1,000

consecutive patients will be presented.

4:30 KEYNOTE PRESENTATION:

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

The challenges and opportunities of implementing a broad

genotyping assay in routine clinical management of cancer

patients will be discussed. Snapshot was launched over 3

years ago at the Massachusetts General Hospital, with the

goal of providing all cancer patients with a genetic fingerprint

to guide therapeutic decisions. Lessons learned will be

outlined, and a roadmap to effectively move testing forward

into the Next Gen sequencing era.

5:00 Breakout Discussions (See Web for Details)

6:00 Close of Day

Tuesday, February 12

8:00 am Morning Coffee

Data Management and Analysis

8:10 Chairperson’s Remarks

8:15 Under the Hood of the 1000 Genomes Project

Mark A. DePristo, Ph.D., Associate Director, Medical

and Population Genetics Analysis, Broad Institute of MIT

and Harvard (on behalf of The 1000 Genomes Project

Consortium)

This presentation discusses the evolution of the nextgeneration

sequencing (NGS) data underlying the public

1000 Genomes Project resource, from some of the earliest

technologies of 2009 to today’s state-of-the-art data. It

will also highlight key NGS analytic advances originating

from the Project.

8:45 Delivering Genomic Medicine: Challenges

and Opportunities

Heidi L. Rehm, Ph.D., FACMG, Assistant Professor,

Pathology, BWH and Harvard Medical School; Director,

Laboratory for Molecular Medicine, Partners Healthcare

Center for Personalized Genetic Medicine

This talk will cover the speaker’s experience in offering clinical

sequencing to patients, from disease-targeted panels to whole

genome analyses as well as supporting the interpretation

and delivery of those results to physicians. It will also cover

approaches to data sharing within the community.

9:15 From Sequence Files to

Sponsored by

Physicians Report and the Tools

Needed to Get There

Martin Seifert, Ph.D., CEO,

Genomatix Software

Providing actionable biology from NGS data in a report useful

to the practicing clinician is difficult. Ensuring the report is

accurate, reproducible, and reflects the biology of the patient

is an even larger task. We will show examples of Genomatix’

approach to these issues and how we successfully ensure a

secure, accurate, and reproducible report, bridging the gap

from sequencer to clinician.

9:30 Rapid Identification of

Sponsored by

Disease Causative Mutations

Ali Torkamani, Ph.D., Co-Founder & CSO,

Cypher Genomics

Recent successes in clinical genome sequencing have

highlighted the potential for sequencing to greatly improve

molecular diagnosis and clinical decision-making. However,

these successes have relied upon large bioinformatics teams

and in-depth literature surveys. We will demonstrate how the

Cypher Genomics software service can quickly return a small

set of well-annotated genetic variants most likely to contribute

to a patient’s disease.

10:00 Coffee Break with Exhibit and

Poster Viewing

Getting Genomic Testing to Clinic

10:30 Sequence Data on Demand: Access,

Visualization and Communication of Genome

Sequence Data between Physicians, Researchers,

and Patients

Sitharthan Kamalakaran, Ph.D., Senior Member, Research

Staff, Philips Research North America

Patients’ genome sequences are informative for clinical care

over the patient’s lifetime and not just for the diagnosis at

hand. We present a web-accessible interface for clinicians to

integrate relevant patient genome data in their routine practice

through clinically-framed queries.

11:00 Targeted Next Generation Sponsored by

Sequencing in FFPE Tumor Samples:

Distilling High Quality Information from Low

Quality Samples

Sachin Sah, Senior Scientist, Diagnostics Research

Development, Asuragen, Inc.

SuraSeq™ PCR-based enrichment procedures enable accurate

and sensitive mutation detection from nanogram inputs of

challenging FFPE tumor DNA. Case studies will be presented

that highlight the use of complementary NGS platforms and

novel bioinformatics for discovery and confirmation studies.

11:30 Transitioning New Technologies from the Bench to the Bedside: Direct Fetal Testing Using Circulating

Cell-Free DNA

Allan T. Bombard, M.D., CMO, Sequenom

This presentation will address clinical test implementation of new tests in the US, using circulating

cell-free DNA for noninvasive

prenatal testing (NIPT) of fetal aneuploidy from maternal plasma as an example.

12:00 Moving Genomic Screening to the Clinic: Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara Crews Finley Chair in Medical Genetics; Professor and Chair,

Department of Genetics; Director, Heflin Center for Genomic Sciences, University of Alabama at Birmingham

Since the sequencing of the human genome there has been an expectation that a flood of advances would find their

way to the clinic, and, indeed, the pace of translation of genomics to clinical application is accelerating. It is likely that the future of

medical care will evolve by the convergence of two disruptive technologies – that of information science and genomics, which, in a

sense can be viewed as one and the same.

12:30 pm Close of Symposium

Featured Presentations

Genomically-Supported Diagnostic and

Drug Reposition Strategies out of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center

for Applied Genomics, Children’s Hospital of

Philadelphia

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

Moving Genomic Screening to the Clinic:

Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara

Crews Finley Chair in Medical Genetics;

Professor and Chair, Department of Genetics;

Director, Heflin Center for Genomic Sciences,

University of Alabama at Birmingham

Reasons to Attend

• Hear keynote presentations from Dr. Hakon

Hakonarson of CHOP and Dr. John Iafrate of MGH

• Find out how to transition genomic

screening to the clinic

• Discover evolving approaches to

mutation detection

• Explore data management and analysis solutions

• Learn the role of pharmacogenomics in

patient care

• Network with genomic thought leaders

• Par ticipate in interactive, problem-solving

breakout discussions

TriConference.com

February 11-15 • Moscone North Convention Center • San Francisco, CA

2013

Molecular Med

Tri-Con

Premier Sponsors:

2 Genomics in Medicine

Plenary Keynotes 2013 Sponsors

Wednesday, February 13 8:00 – 9:40 am

Personalized Oncology – Fulfilling the Promise for

Today’s Patients

In honor of the 20th anniversary of the Molecular Medicine Tri-conference, CHI and

Cancer Commons will present a plenary panel on Personalized Oncology. Innovations

such as NGS and The Cancer Genome Atlas have revealed that cancer comprises

hundreds of distinct molecular diseases. Early clinical successes with targeted

therapies suggest that cancer might one day be managed as a chronic disease using

an evolving cocktail of drugs. Representing all five conference channels, Diagnostics,

Therapeutics, Clinical, Informatics, and Cancer, a panel of experts will lead a highly

interactive exploration of what it will take to realize this vision in the near future.

Moderator: Marty Tenenbaum, Ph.D., Founder and Chairman, Cancer

Commons; Prominent AI Researcher; Cancer Survivor

Tony Blau, M.D., Professor, Department of Medicine/Hematology and

Adjunct Professor, Department of Genome Sciences, University of

Washington; Attending Physician, Seattle Cancer Care Alliance; Co-

Director, Institute for Stem Cell and Regenerative Medicine, University of

Washington and the Program for Stem and Progenitor Cell Biology at the

UW/FHCRC Cancer Consortium; Founder and Scientific Officer, Partners

in Personal Oncology

Sarah Greene, Executive Director, Cancer Commons

Laurence Marton, M.D., Adjunct Professor, Department of Laboratory

Medicine, University of California San Francisco; former Dean of

Medicine, University of Wisconsin

Jane Reese-Coulbourne, MS, ChE, Executive Director, Reagan-Udall

Foundation for the FDA; former Board Chair, Lung Cancer Alliance;

Cancer Survivor

Anil Sethi, CEO, Pinch Bio; HL7 Pioneer and Health Informatics

Entrepreneur

Joshua Stuart, Ph.D., Associate Professor, Department of Biomolecular

Engineering, University of California Santa Cruz

Thursday, February 14 8:00 – 9:40 am

Plenary Keynote Panel: Emerging Technologies &

Industry Perspectives

This session features a series of presentations on emerging and hot technologies in

diagnostics, drug discovery & development, informatics, and oncology. Interactive

Q&A discussion with the audience will be included.

Moderator: To be Announced

Gregory Parekh, Ph.D., CEO, Biocartis

Kevin Bobofchak, Ph.D., Pathway Studio Product Manager, Elsevier

Jeremy Bridge-Cook, Ph.D., Senior Vice President, Research &

Development, Luminex Corporation

Panelist to be Announced, Remedy Informatics

Harry Glorikian, Managing Partner, Scientia Advisors, LLC

Lynn R. Zieske, Ph.D., Vice President, Commercial Solutions, Singulex, Inc.

Sponsored by

Premier Sponsors:

Corporate Sponsors:

Molecular

Corporate Support Sponsors:

TriConference.com 3

Conference Programs:

Feb 13-15

Diagnostics Channel

Molecular Diagnostics

Personalized Diagnostics

Cancer Molecular Markers

Circulating Tumor Cells

Digital Pathology – NEW

Companion Diagnostics – NEW

Therapeutics Channel

Mastering Medicinal Chemistry

Cancer Biologics

Clinical and Translational Science

Clinical Channel

Oncology Clinical Trials

Clinical and Translational Science

Clinical Sequencing – NEW

Informatics Channel

Bioinformatics in the Genome Era

Integrated R&D Informatics and Knowledge Management

Cancer Channel

Cancer Molecular Markers

Circulating Tumor Cells

Predictive Pre-Clinical Models in Oncology – NEW

Oncology Clinical Trials

Cancer Biologics

Symposia*:

Feb 11-12

Targeting Cancer Stem Cells

Genomics in Medicine – NEW

Point-of-Care Diagnostics

Quantitative Real-Time PCR – NEW

Next Generation Pathology

Partnering Forum*:

Feb 11-12

Emerging Molecular Diagnostics

Short Courses*:

Feb 12

1:30-4:30pm

SC1 Identification & Characterization of Cancer Stem Cells

SC2 Commercialization Boot Camp: Manual for Success in

the Molecular Diagnostics Marketplace

SC3 NGS Data and the Cloud

SC4 Best Practices in Personalized and Translational

Medicine

SC5 Latest Advances in Molecular Pathology

SC6 Regulatory Approval of a Therapeutic & Companion

Diagnostic: Nuts & Bolts

SC7 PCR Part I: qPCR in Molecular Diagnostics

SC8 Data Visualization

SC9 Methods for Synthesis & Screening of Macrocyclic

Compound Libraries

5:00-8:00pm (Dinner)

SC10 PCR Part II: Digital PCR Applications and Advances

SC11 Sample Prep and Biorepositories for Cancer Research

SC12 Next-Generation Sequencing in Molecular Pathology:

Challenges and Applications

SC13 Strategies for Companion Diagnostics Development

SC14 Patient-Derived Cancer Tissue Xenograph Models

SC16 Microfluidics Technology and Market Trends

SC17 Open Cloud & Data Science

Get the best 5-day value! Our All Access

Packages is a convenient, cost-effective way

to attend each aspect of Molecular Med

TRI-CON 2013. Package includes access to

1 Symposium or Partnering Forum, 2 Short

Courses and 1 Conference Program.

TRI-CON All Access Package

*Separate reg required with a la carte pricing

Co-located Event

4 Genomics in Medicine

Inaugural Genomics in Medicine

Monday, February 11

7:30 am Registration and Morning Coffee

8:25 Chairperson’s Opening Remarks

Screening for Rare and

Difficult to Diagnose Diseases

8:30 KEYNOTE PRESENTATION:

Genomically-Supported Diagnostic and

Drug Reposition Strategies out

of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center for Applied

Genomics, Children’s Hospital of Philadelphia

This talk will discuss genomic strategies applied in academia

to identify subsets of patients who, based on their genetic

make-up, are predicted to have a favorable response profile to

drugs that come from reposition opportunities.

9:00 Evolving Approaches to Mutation Detection in

Rare Diseases

Tom Scholl, Vice President, Research & Development,

Integrated Genetics, LabCorp

Emerging trends in this field that include the expansion of

content in clinical tests to include many loci and increased

clinical sensitivity by expanding numbers of mutations detected

or whole gene sequencing will be presented.

9:30 From Raw Sequencing Data to

Functional Interpretation

Daniel MacArthur, Ph.D., Group Leader, Analytic and

Translational Genetics Unit, Massachusetts General Hospital

This presentation will discuss the key lessons learned

from large-scale sequencing studies in both common and

rare diseases with a particular focus on finding mutations

underlying severe muscle diseases.

10:00 Coffee Break with Exhibit and Poster Viewing

10:30 Providing Whole Genome Sequencing in the Clinic

David Dimmock, M.D., Assistant Professor, Pediatrics,

Medical College of Wisconsin

This presentation will focus on advances in the implementation

of genome wide sequencing in clinical practice. It will address

counseling and consent issues specific to testing children.

Specifically, it will highlight the challenges of execution in the

acute care setting.

11:00 Clinical Utility of Whole Exome Sequencing

Christine M. Eng, M.D., Professor, Department of Molecular

and Human Genetics, Baylor College of Medicine

This presentation will discuss the role of whole exome

sequencing in the diagnostic evaluation of patients with

challenging phenotypes of genetic etiology. Examples of

clinical utility, directed medical care, and cost-effectiveness

of the whole exome approach to clinical diagnostics will be

presented.

11:30 A Neuronal Carnitine Deficiency Hypothesis

for Autism

Arthur L. Beaudet, M.D., Henry and Emma Meyer Professor

and Chair, Department of Molecular and Human Genetics,

Baylor College of Medicine

We have published a paper entitled “A common X-linked

inborn error of carnitine biosynthesis may be a risk factor for

nondysmorphic autism” (PMID: 22566635). We propose a

neuronal carnitine deficiency hypothesis as one risk factor

or cause for autism whereby 10-20% of autism might

be preventable.

12:00 pm Luncheon Presentation

(Sponsorship Opportunity Available) or Lunch on

Your Own

Predictive Tests for

Improved Patient Outcomes

1:25 Chairperson’s Remarks

1:30 Implementation of Personalized Healthcare into

Clinical Practice: Lessons Learned

Kathryn Teng, M.D., FACP, Director, Center for Personalized

Healthcare, Cleveland Clinic

Integrating a pharmacogenetics program into clinical practice

requires a vision for the future of healthcare and a roadmap to

reach that vision. Pioneering the road to achieving this vision

has brought challenges and has allowed for the creation of

solutions that might be applied universally.

2:00 Molecular Profiling of Tumors to Select Therapy

in Patients with Advanced Refractory Tumors

Ramesh Ramanathan, M.D., Medical Director, The Virginia

G. Piper Cancer Center Clinical Trials

This presentation will discuss molecular profiling of tumors

using IHC, CGH and whole genome/exome sequencing of

tumors to find actionable targets for therapy. Clinical trials

and case reports of patients treated by this approach will

be presented.

2:30 Sponsored Presentations (Opportunities Available)

3:00 Refreshment Break with Exhibit and

Poster Viewing

3:30 Gene Panels vs. Whole Exome Sequencing in

Cancer Molecular Testing

Madhuri Hegde, Ph.D., FACMG, Associate Professor, Senior

Director, Emory Genetics Laboratory, Department of Human

Genetics, Emory University School of Medicine

TriConference.com 5

Individualized Care for Improved Outcomes

4:00 Next Generation Sequencing and

Cancer Diagnostics

Phil Stephens, Ph.D., Vice President, Cancer Genomics,

Foundation Medicine

Foundation Medicine has developed FoundationOne™, a

CLIA-certified, comprehensive cancer genomic test that

analyzes routine clinical specimens for somatic alterations in

189 relevant cancer genes. Experience with the initial 1,000

consecutive patients will be presented.

4:30 KEYNOTE PRESENTATION:

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

The challenges and opportunities of implementing a broad

genotyping assay in routine clinical management of cancer

patients will be discussed. Snapshot was launched over 3

years ago at the Massachusetts General Hospital, with the

goal of providing all cancer patients with a genetic fingerprint

to guide therapeutic decisions. Lessons learned will be

outlined, and a roadmap to effectively move testing forward

into the Next Gen sequencing era.

5:00 Breakout Discussions (See Web for Details)

6:00 Close of Day

Tuesday, February 12

8:00 am Morning Coffee

Data Management and Analysis

8:10 Chairperson’s Remarks

8:15 Under the Hood of the 1000 Genomes Project

Mark A. DePristo, Ph.D., Associate Director, Medical

and Population Genetics Analysis, Broad Institute of MIT

and Harvard (on behalf of The 1000 Genomes Project

Consortium)

This presentation discusses the evolution of the nextgeneration

sequencing (NGS) data underlying the public

1000 Genomes Project resource, from some of the earliest

technologies of 2009 to today’s state-of-the-art data. It

will also highlight key NGS analytic advances originating

from the Project.

8:45 Delivering Genomic Medicine: Challenges

and Opportunities

Heidi L. Rehm, Ph.D., FACMG, Assistant Professor,

Pathology, BWH and Harvard Medical School; Director,

Laboratory for Molecular Medicine, Partners Healthcare

Center for Personalized Genetic Medicine

This talk will cover the speaker’s experience in offering clinical

sequencing to patients, from disease-targeted panels to whole

genome analyses as well as supporting the interpretation

and delivery of those results to physicians. It will also cover

approaches to data sharing within the community.

9:15 From Sequence Files to

Sponsored by

Physicians Report and the Tools

Needed to Get There

Martin Seifert, Ph.D., CEO,

Genomatix Software

Providing actionable biology from NGS data in a report useful

to the practicing clinician is difficult. Ensuring the report is

accurate, reproducible, and reflects the biology of the patient

is an even larger task. We will show examples of Genomatix’

approach to these issues and how we successfully ensure a

secure, accurate, and reproducible report, bridging the gap

from sequencer to clinician.

9:30 Rapid Identification of

Sponsored by

Disease Causative Mutations

Ali Torkamani, Ph.D., Co-Founder & CSO,

Cypher Genomics

Recent successes in clinical genome sequencing have

highlighted the potential for sequencing to greatly improve

molecular diagnosis and clinical decision-making. However,

these successes have relied upon large bioinformatics teams

and in-depth literature surveys. We will demonstrate how the

Cypher Genomics software service can quickly return a small

set of well-annotated genetic variants most likely to contribute

to a patient’s disease.

10:00 Coffee Break with Exhibit and

Poster Viewing

Getting Genomic Testing to Clinic

10:30 Sequence Data on Demand: Access,

Visualization and Communication of Genome

Sequence Data between Physicians, Researchers,

and Patients

Sitharthan Kamalakaran, Ph.D., Senior Member, Research

Staff, Philips Research North America

Patients’ genome sequences are informative for clinical care

over the patient’s lifetime and not just for the diagnosis at

hand. We present a web-accessible interface for clinicians to

integrate relevant patient genome data in their routine practice

through clinically-framed queries.

11:00 Targeted Next Generation Sponsored by

Sequencing in FFPE Tumor Samples:

Distilling High Quality Information from Low

Quality Samples

Sachin Sah, Senior Scientist, Diagnostics Research

Development, Asuragen, Inc.

SuraSeq™ PCR-based enrichment procedures enable accurate

and sensitive mutation detection from nanogram inputs of

challenging FFPE tumor DNA. Case studies will be presented

that highlight the use of complementary NGS platforms and

novel bioinformatics for discovery and confirmation studies.

NEW

TriConference.com 6

Recommended Programs:

Main Conference

• Personalized Diagnostics

Short Courses

• NGS Data and the Cloud

• PCR Part I: qPCR in Molecular Diagnostics

• NGS in Molecular Pathology

• PCR Part II: Digital PCR Applications and Advances

11:30 Transitioning New Technologies from the Bench to the Bedside: Direct Fetal Testing Using Circulating

Cell-Free DNA

Allan T. Bombard, M.D., CMO, Sequenom

This presentation will address clinical test implementation of new tests in the US, using circulating cell-free DNA for noninvasive

prenatal testing (NIPT) of fetal aneuploidy from maternal plasma as an example.

12:00 Moving Genomic Screening to the Clinic: Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara Crews Finley Chair in Medical Genetics; Professor and Chair,

Department of Genetics; Director, Heflin Center for Genomic Sciences, University of Alabama at Birmingham

Since the sequencing of the human genome there has been an expectation that a flood of advances would find their

way to the clinic, and, indeed, the pace of translation of genomics to clinical application is accelerating. It is likely that the future of

medical care will evolve by the convergence of two disruptive technologies – that of information science and genomics, which, in a

sense can be viewed as one and the same.

12:30 pm Close of Symposium

7 Genomics in Medicine

Hotel Information

Reserve your hotel and save $100 off

your conference registration*

*You must book your reservation under the Tri-Conference

room block for a minimum of 4 nights at the Marriott or the

Intercontinental Hotel. One discount per hotel room.

Conference Venue:

The Moscone North Convention Center

747 Howard Street

San Francisco, CA 94103

http://www.moscone.com

Please visit TriConference.com to make your

reservations online or call the hotel directly to

reserve your sleeping accommodations.You will

need to identify yourself as a Molecular Med Tri-Con

attendee to receive the discounted room rate with

the host hotel. Reservations made after the cut-off

date or after the group room block has been filled

(whichever comes first) will be accepted on a spaceand

rate-availability basis. Rooms are limited, so

please book early.

Sponsorship &

Exhibit Opportunities

CHI offers comprehensive sponsorship packages which include presentation

opportunities, exhibit space and branding, as well as the use of

the pre and post-show delegate lists. Signing on early will allow you to

maximize exposure to hard-to-reach decision makers.

Breakfast & Luncheon Presentations

Opportunities may include a 15 or 30-minute podium presentation

during the main agenda. Boxed lunches are delivered into the main

session room, which guarantees audience attendance and participation.

Packages include: exhibit space, on-site branding, and more.

Invitation-Only VIP Dinner/Private Receptions

Sponsors will select their top prospects from the conference preregistration

list for an evening of networking at the hotel or at a choice

local venue. CHI will extend invitations and deliver prospects. Evening

will be customized according to sponsor’s objectives.

Exhibit

Exhibitors will enjoy facilitated networking opportunities with 3,000

highly-targeted delegates at the overall event. Speak face-to-face with

prospective clients and showcase your latest product, service, or solution.

Inquire about additional branding

opportunities, including our

Valentine’s Day Soiree sponsorship!

Looking for additional ways to drive leads to

your sales team? CHI can help!

We offer clients numerous options for custom lead generation programs

to address their marketing and sales needs, including:

• Live Webinars

• White Papers

• Market Surveys

• Podcasts and More!

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Gene Therapy Into Healthy Heart Muscle: Reprogramming Scar Tissue In Damaged Hearts

Posted in Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Cardiac & Vascular Repair Tools Subsegment, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, Human Immune System in Health and in Disease, Molecular Genetics & Pharmaceutical, Origins of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Resident-cell-based, Stem Cells for Regenerative Medicine, tagged , , , , , , on January 9, 2013| 6 Comments »

Reporter: Aviva Lev-Ari, PhD, RN

Scar Tissue In Damaged Hearts Reprogrammed By Gene Therapy Into Healthy Heart Muscle

Article Date: 08 Jan 2013 – 0:00 PST

A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect, said researchers from Weill Cornell Medical College, Baylor College of Medicine and Stony Brook University Medical Center in a report that appears online in the Journal of the American Heart Association. 

“The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting,” said Dr. Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report’s corresponding author. “The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene.” 

“This experiment is a proof of principle,” said Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College and a pioneer in gene therapy, who played an important role in the research. “Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts.” 

During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure. 

Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, Rosengart and his colleagues transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material. (A transcription factor binds to specific DNA sequences and starts the process that translates the genetic information into a protein.) 

The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart.) 

The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer. 

Rosengart emphasizes that more work needs to be completed to show that the effect of the VEGF is real, but it has real promise as part of a new treatment for heart attack that would minimize heart damage. 

“We have shown both that GMT can effect change that enhances the activity of the heart and that the VEGF gene is effective in improving heart function even more,” said Dr. Crystal. 

The idea started with the notion of induced pluripotent stem cells – reprograming mature specialized cells into stem cells that are immature and can differentiate into different specific cells needed in the body. Dr. Shinya Yamanaka and Sir John B. Gurdon received the Nobel Prize in Medicine and Physiology for their work toward this goal this year. 

However, use of induced pluripotent stem cells has the potential to cause tumors. To get around that, researchers in Dallas and San Francisco used the GMT cocktail to reprogram the scar cells into cardiomyocytes (cells that become heart muscle) in the living animals. 

Now Rosengart and his colleagues have gone a step farther – encouraging the production of new blood vessels to provide circulation to the new cells.

REFERENCES:

Others who took part in this work include Megumi Mathison, Ronald Gersch, Ahmed Nasser, Sarit Lilo, Mallory Korman, Mitchell Fourman, Kenneth Shroyer, Jianchang Yang, Yupo Ma, all of Stony Brook University Medical Center and Neil Hackett of Weill Cornell Medical College.
Funding for this work came from the generosity of James and Lisa Cohen.
Weill Cornell Medical College

CITATIONS:

MLA

n.p. “Scar Tissue In Damaged Hearts Reprogrammed By Gene Therapy Into Healthy Heart Muscle.” Medical News Today. MediLexicon, Intl., 8 Jan. 2013. Web.
9 Jan. 2013. <http://www.medicalnewstoday.com/releases/254618.php>

APA

n.p. (2013, January 8). “Scar Tissue In Damaged Hearts Reprogrammed By Gene Therapy Into Healthy Heart Muscle.” Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/254618.php.

SOURCE:

http://www.medicalnewstoday.com/releases/254618.php 

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Transcription Factor Lyl-1 Critical in Producing Early T-Cell Progenitors

Posted in Biological Networks, Gene Regulation and Evolution, CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, tagged , , , , on July 8, 2012| 2 Comments »

Reporter: Prabodh Kandala, PhD.

A transcription factor called Lyl-1 is necessary for production of the earliest cells that can become T-cells, critical cells born in the thymus that coordinate the immune response to cancer or infections, said a consortium of researchers led by those from Baylor College of Medicine in a report in the journal Nature Immunology.

These earliest progenitors (called early T lineage progenitor cells) are the first cells that can be identified as being on the road to becoming T-cells, said Dr. Margaret Goodell, director of the Stem Cells and Regenerative Medicine Center of Baylor College of Medicine. Without Lyl-1, only a few of these early T lineage progenitor cells get made.

“This finding gives us insight into the biology of these progenitor cells,” said Goodell, a professor of pediatrics at BCM and a member of the Center for Cell and Gene Therapy at BCM, Texas Children¹s Hospital and The Methodist Hospital.

Dr. Fabian Zohren, a post-doctoral student in Goodell¹s laboratory, found that mice lacking the gene for this factor had a T-cell deficiency and in particular, too few of these early progenitor cells.

“It showed that those early T lineage progenitor cells are really dependent on Lyl-1 for their generation,” said Goodell, who is also corresponding author of the report. “We think that Lyl-1 controls a program that allows survival and expansion of these critical progenitors.”

The finding may have particular import in understanding a form of leukemia known as T-cell acute lymphoblastic leukemia. The researchers found that the forms of the disease that have the worst prognosis are those in which the cancer cells resemble these early T lineage progenitor cells. These cells also have high levels of Lyl-1.

One possibility is the T-cell progenitors in patients with this type of T-cell leukemia continue to express Lyl-1, so continue to be programmed to expand. The excess Lyl-1 prevents the early T lineage progenitor cells from differentiating into active T-cells. Goodell said a recent grant from the Alex¹s Lemonade Stand Foundation will help test that hypothesis.

Abstract:

Thymopoiesis depends on the recruitment and expansion of bone marrow–derived progenitor populations; tight regulation of these processes is required for maintenance of the homeostasis of the T lineage. Lyl-1, a transcription factor that regulates hematopoietic progenitors, is expressed in thymocyte progenitors until T cell commitment. Here we demonstrate a requirement for Lyl-1 in lymphoid specification and the maintenance of early T lineage progenitors (ETPs). Lyl-1 deficiency resulted in profound defects in the generation of lymphoid-primed multipotent progenitors (LMPPs), common lymphoid progenitors (CLPs) and ETPs. Lyl-1-deficient ETPs and thymocyte progenitors at the CD4−CD8− double-negative 2 (DN2) stage showed more apoptosis, blocked differentiation and impaired population expansion. We identified Gfi1 as a critical transcriptional target of Lyl-1-mediated lymphopoiesis of T cells. Thus, Lyl-1 is a pivotal component of a transcriptional program that controls the lymphoid specification and maintenance of ETPs.

Ref:

http://www.sciencedaily.com/releases/2012/07/120708162320.htm

http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.2365.html.

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