National Advisory Council for Human Genome Research
Summary of Meeting

Fishers Lane Conference Center
Rockville, Md.

February 7, 2005

The open session of the National Advisory Council for Human Genome Research was convened for its forty-third meeting at 8:35 a.m.. on February 7, 2005 at the Fishers Lane Conference Center, Rockville, Md. Francis Collins, Director of the National Human Genome Research Institute, called the meeting to order.

The meeting was open to the public from 8:35 a.m. until 3:32 p.m. on February 7, 2005. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 3:32 p.m. on February 7, 2005 until adjournment for the review, discussion, and evaluation of grant applications.

Council members present:

Marilyn Coors
Geoff Duyk, by phone
Sean Eddy
Beverly Gaines
William Gelbart
Eric Juengst
Bronya Keats
Jeffrey Murray
Richard Myers
Robert Tepper, by phone
George Weinstock
Tadataka Yamada

Council members absent:

David Burgess
Vicki Yates Brown
Mary Hendrix

Ex Officio member absent:

Gerry Schellenberg

Staff from the National Human Genome Research Institute:

Chris Austin, OD
Vence Bonham, OD
Joy Boyer, DER
Lisa Brooks, DER
Comfort Browne, DER
Brian Campbell, DER
Cheryl Chick, DER
Monika Christman, DER
Francis Collins, OD
Tanya Dougans, DER
Elise Feingold, DER
Adam Felsenfeld, DER
Peter Good, DER
Bettie Graham, DER
Alan Guttmacher, OD
Mark Guyer, DER
Linda Hall, DER
John Hodges Howell, DER
Jean Jenkins, OD
Shira Katseff, DER
Tim Leshan, OD
Laura Liefer, DER
Jean McEwen, DER
James McWilliams, DER
Jessica Melone, DER
Mark Moore, DER
Patrick Nailer, DER
Ken Nakamura, DER
Taiwo Oladapo, DEAS
Vivan Ota Wang, DER
Brad Ozenberger, DER
Allison Peck, DER
Jane Peterson, DER
David Rees, OD
Eddie Rivera, OD
Jerry Roberts, DER
Laura Rodriguez, OD
Jeff Schloss, DER
Michael Shi, DER
Shundel Stephenson, DEAS
Gary Temple, DER
Larry Thompson, OD
Elizabeth Thomson, DER
Susan Vasquez, OD
Fred Walker, OD
Kris Wetterstrand, DER
Diane Williams-Bey, DEAS
Jonathan Witonsky, DER
Lynn Zacharia, DER

Others present for all or a portion of the meeting:

Andrea Beckel-Mitchener, NIMH
Joann Boughman, American Society of Human Genetics
Ping Fan, CSR
Molly Laas, The Blue Sheet
Jose Ruiz, Office of the Director, NIH
Sharon Terry, Genetic Alliance
Wendy Uhlmann, National Society of Genetic Counselors

Introduction of Liaisons and New Employees

Mark Guyer introduced Sharon Terry from the Genetic Alliance, Joann Boughman from the American Society of Human Genetics and Wendy Uhlmann from the National Society of Genetic Counselors. Dr. Guyer also introduced Mark Moore, a contractor working on a new project in DER, and Jose Ruiz from the NIH Director's office.

Approval of Minutes

The minutes from the September 2004 Council meeting were approved as submitted.

Future Meeting Dates

The following dates were proposed for future meetings: February 7-8, 2005, May 23-24, 2005, September 12-13, 2005, February 12-14, 2005, May 22-23, 2006 and September 11-12, 2006, and February 12-13, 2007.

Director's Report

General Announcements

On January 26th, 2005, Mike Leavitt was confirmed as Secretary of Health and Human Services, replacing former secretary Tommy Thompson. Mr. Leavitt has previously served in the Federal Government as the Administrator of the Environmental Protection Agency. Previously, he was the governor of Utah.

Maurice Wilkins passed away on October 5th, 2004 at the age of 88. Dr. Wilkins shared the Nobel Prize with Jim Watson and Francis Crick in 1962. Maclyn McCarty passed away on January 2nd, 2005 at the age of 93. Dr. McCarty worked with Oswald Avery and Colin MacLeod in the 1940s on "the transforming principle," revolutionary research that proved that genes are made of DNA. Although their research was never nominated for a Nobel Prize, without it, Watson and Crick would likely not have divined the structure of the double helix. Another distinguished figure in the field of evolutionary biology, Ernst Mayr, died at the age of 100.

On Monday October 24th, NIH announced the appointment of David A. Schwartz as the new director of the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program (NTP). Dr. Schwartz was previously the director of the Pulmonary, Allergy, and Critical Care Division and Vice Chair of Research in the Department of Medicine at Duke University, where he played a principal role in developing three interdisciplinary Centers, in Environmental Health Sciences, Environmental Genomics, and Environmental Asthma. Dr. Schwartz replaces Kenneth Olden, Ph.D., who led NIEHS since 1991; Dr. Olden will remain as a researcher in the NIEHS intramural program. Dr. Schwartz will join NIH on April 4, 2005.

On February 1st, 2005, NIH announced the appointment of Elizabeth G. Nabel, M.D as the new director of the National Heart, Lung, and Blood Institute (NHLBI). Dr. Nabel, who most recently served as the Scientific Director of Clinical Research in the NHLBI intramural program, began her appointment as director on February 1, 2005. She previously worked at the University of Michigan. Dr. Nabel's intramural lab, which focuses on the development of novel genetic and cellular therapies for cardiovascular disease, will be located in the Genome Technology Branch of NHGRI.

On February 1st, Dr. Zerhouni announced a new supplemental ethics regulation that will affect all NHGRI employees, which was drafted for NIH by the HHS Designated Agency Ethics Official and the HHS Office of General Counsel. The new regulation includes a moratorium on outside consulting with pharmaceutical and biotechnology companies, restrictions on the receipt of awards, and restrictions and/or prohibitions on the amount of stock individual employees may hold in pharmaceutical and biotechnology companies. The new regulations are interim, with opportunity for reassessment of their effects in one year. All intramural researchers have to terminate outside positions within 30 days. All NIH staff must divest stocks to a $15,000 "de minimus" level, and many holding senior positions must divest themselves completely. This new policy could have a large effect on retaining and recruiting intramural staff.

Rick Myers pointed out that most of the conflict of interest violations occurred in clinical trial studies; however, NHGRI intramural scientists concentrate mainly on basic science. There has been no distinction made between different types of research for the new regulations. The Blue Ribbon Panel that was convened to discuss the conflict of interest concerns concluded that many of the scientists' relationships with industry were actually beneficial; however, there is much concern in the Congress, the public, and the press about NIH scientists' behavior. The regulations are stiff, but will likely not be changed soon.

On September 28th, NIH announced the first nine recipients of the NIH Director's Pioneer Award, a central component of the NIH Roadmap for Medical Research. The program is designed to support individual scientists and thinkers with highly innovative ideas and approaches to contemporary challenges in biomedical research. Each of the nine recipients will receive an award of $500,000 in direct costs per year for five years. Among this year's recipients is Dr. Steven Quake, who was supported by NHGRI with a FIRST (R29) award for new investigators in 1997 for his work in developing integrated nanofluidic chip systems and novel chemistry for single molecule DNA sequencing. A result of that project is what appears to be the first published report of single molecule DNA sequencing (Proceeds of the National Academy of Sciences (PNAS) 2003. 100:3980).

The 2004 MacArthur Fellows program awardees included three genomic scientists: Joseph DeRisi (Associate Professor of Biochemistry and Biophysics, UCSF), Vamsi Mootha (Assistant Professor of Systems Biology, Harvard Medical School), and Daphne Koller (Associate Professor of Computer Science, Stanford University).

Alan Guttmacher (Deputy Director, NHGRI) and Robert Nussbaum (Senior Investigator and Chief Genetic Disease Research Branch, Inherited Disease Branch, NHGRI) were elected to the Institute of Medicine this past October.

Dr. Collins attended the World Economic Forum annual meeting in Davos, Switzerland January 26th to 30th, 2005. Dr. Collins is a member of the organizing committee for scientific aspects of this meeting. This year, there was a strong focus on the developed world assisting the undeveloped world. Global warming, biodefense, AIDS, malaria, and TB were discussed in the scientific sessions. The representation of scientists was not as strong as it might have been, given the elevated place of science in the discussion.

Peter H. Byers is the new president of the American Society of Human Genetics. Dr. Byers is Professor of Pathology and of Medicine and Adjunct Professor of Genome Sciences at the University of Washington in Seattle, WA. Dr. Byers met with senior NHGRI staff on January 11th, 2005. The cordial and productive working relationship between ASHG and NHGRI will continue.

New NHGRI Initiatives

Several new NHGRI initiatives have been released. One of these, the K23 training solicitation with Emphasis on Therapeutic Interventions Employing Genomic or Proteomic Technologies, is a patient-oriented research career development award to promote adequate mentoring with regards to clinical and basic science research. Another new initiative, Molecular Screening Assay Development for Sickle Cell Disease (RFA-HG-05-001), encourages the development of assays that will be appropriate for screening by the NIH Roadmap Molecular Libraries Screening Centers Network initiative. There was also an RFP released for mouse knockouts. This is an effort by the NIH to procure mouse knockout strains that have been generated and phenotyped; awards will be made by April or May.

Recent Scientific Accomplishments and Issues

NHGRI - Extramural Program

Sequencing. In October 2004, the International Human Genome Sequencing Consortium published a paper describing the high quality finished human genome sequence that was completed in April 2003. The finished sequence now covers more than 99 percent of the euchromatic (or gene-containing) portion of the human genome and was sequenced to an accuracy of 99.999 percent. The number of human protein-coding genes is now estimated at 20,000-25,000.

Two sets of new awards in the area of sequencing technology development were funded since the last Council meeting. Under the "$100,000 genome" program, ten awards were made that will support research to develop new technologies to lower dramatically the cost of DNA sequencing. Some of the awards will be directed at the development of full sequencing systems, while others will focus on novel components or improvements for existing systems. Under the "$1,000 genome" program, four feasibility projects were funded to test new fabrication and detection methods. In combination with similar grants awarded earlier in the year, NHGRI made a total of twenty awards for sequencing technology development in FY 2004, for a total of a $32 million investment in the $100,000 genome goal and a $6.5 million investment in the $1,000 genome goal over the lifetime of the grants. More applications submitted in response to these RFAs will be discussed at the May council meeting.

The status of organisms in the NHGRI-funded pipeline was detailed in a handout. A 3.3-fold coverage draft of the bovine genome was assembled in October 2004 and a first analysis of the chicken genome (6.6-fold draft) was published in December 2004. The Mouse Genome Sequencing Consortium is on schedule to finish the mouse genome sequence by the end of calendar 2005.

The NHGRI Division of Extramural Research is examining the possibility of a human "medical sequencing" program. The Institute organized a workshop on January 5-6, 2005 to discuss a proposal for a pilot project to collect sequence information from a large number of individuals, as the tool of large-scale sequencing transitions from basic applications to clinical applications. Several protocols for a pilot study were discussed, including targeted resequencing and whole genome shotgun sequencing; collection of samples from unidentified individuals (e.g., HapMap samples) or individuals with known (medical) phenotypes; and disease-related phenotypes including common diseases, reproductive lethals, and rare recessives. Many questions, in both scientific and ELSI areas, remain after the workshop. NHGRI staff has formulated a plan, involving the organization of a Medical Sequencing Working Group, to pursue these issues.

Dr. Myers asked about the technology discussion at the January meeting. New, potentially disruptive technologies were discussed. There are several that are currently under development, both in the academic sector with NHGRI funding and in the private sector. None of them are available yet, but some people are confident that they will soon be. A major question that the NHGRI is trying to address as it plans the future direction of the sequencing program is how can we design a future for the program that both generates important biological data and drives the technology forward in an effective way. Staff noted that another aspect of the Institute's planning activities for the sequencing program was to obtain proposals from each of the large-scale sequencing centers for how they would spend 10% of their budget on medical resequencing over the next eighteen months. These proposals were reviewed during the administrative site visits carried out last autumn, and the results will be discussed with Council in the closed session.

International HapMap Project
A press release entitled "International HapMap Consortium Expands Mapping Effort" was distributed to the Council. Phase 1 of the HapMap (analysis of the samples from the Yoruba, Han Chinese, Japanese, and CEPH populations) will be finished this month, in February 2005. Phase 2 will involve the low-cost (= one cent per genotype) genotyping of an additional 3 million SNPs, thereby greatly enriching the HapMap; the final HapMap will consist of 4.7M SNPs, or one SNP every 600 bases on average. The Phase II genotyping will be done by Perlegen with support of an NHGRI grant. See below for a fuller description of the status of the HapMap project.

NHGRI awarded six new grants for ENCODE technology development in September 2004. A project description paper about the ENCODE project was published on October 22, 2004 in the "Genes in Action" issue of Science. The ENCODE Consortium has established an Analysis Working group, to be led by Ewan Birney. The third Consortium meeting was held on November 10th and 11th, 2004, in Cold Spring Harbor, NY. The next Consortium meeting is scheduled for July 15th through 19th, 2005 in Rockville, MD. The July meeting will be preceded by a "data fest" that will be organized by the Analysis Working group to carry out the first detailed analysis of existing ENCODE data across the entire project. At the meeting that follows, the results of this analysis will be the basis of a discussion of the status of the project and the issues that need to be addressed in order for the NHGRI to consider scaling up the ENCODE effort to the entire human genome.

Mammalian Gene Collection

The human, mouse, and rat components of the Mammalian Gene Collection project, as well as the associated xenopus and zebrafish projects continue to progress according to schedule. A manuscript summarizing the status of the MGC was published in Genome Research in October, 2004. See below for a fuller description of the status of the MGC.

Mouse Transcriptome

In October 2003, 11 NIH Institutes and Centers, led by NHGRI, funded a comprehensive mouse reference transcriptome project. The aim of this effort was to profile the transcriptomes (all mRNAs) of 90 mouse tissues using the Massively Parallel Signature Sequencing (MPSS) technology. The tissue collection is now complete, and MPSS on 50 of the tissues have been completed so far. Results for these tissues have been deposited at the NCBI Gene Expression Omnibus (GEO) site, A temporary project website also resides at NCBI (, and a more comprehensive project website is under construction. A paper describing the project and initial conclusions from the data will be submitted for publication within the next month.

Centers of Excellence in ELSI Research (CEERs)

The first meeting of the Centers of Excellence in ELSI Research (CEERs) investigators was held in Bethesda on February 3rd and 4th, 2005. The investigators had an opportunity to learn about activities going on in each center and to discuss how they might collaborate with each other. Other discussion topics included how the investigators at the CEERs would interact with other ELSI research activities and with other NHGRI program activities, including the CEGS program; evaluation strategies; and the way in which CEERs could potentially help NHGRI to inform policy decisions.

NHGRI - Intramural Program

On November 10th 2005, NHGRI announced that Dr. Elaine Ostrander had joined NHGRI as the new chief of the Cancer Genetics Branch. Dr. Ostrander came to NHGRI from the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, where for more than a decade her laboratory has been a leader in mapping genes responsible for cancer susceptibility in dogs and humans.

NHGRI is pleased to welcome Dr. Laura Elnitski to the DIR Genome Technology Branch. Dr. Elnitski joins DIR from the Departments of Biology and Computer Science at Penn State University. Dr. Elnitski is a molecular and computational biologist who uses experimental and bioinformatic methods to discover non-coding functional elements in the human genome. In the last 2 years, the intramural program has hired seven tenured investigators, all of whom are women.

NHGRI Office of the Director

Family History Initiative

The U.S. Surgeon General's Family History Initiative was launched on November 8, 2004 to increase awareness about the importance of family history in health, provide tools for communication and evaluation, and increase genomics and health literacy for the American public and their health professionals. A web-based and print tool entitled "My Family Health Portrait" was developed in both English and Spanish to facilitate collection of family history data. The goal was to have Family History Day commence on Thanksgiving, since families traditionally gather together on this day. The event will continue annually in the future. The Office of the Surgeon General, the National Institutes of Health (NIH, NHGRI), the Centers for Disease Control and Prevention (CDC), the Agency for Healthcare Research and Quality (AHRQ), and the Health Resources and Services Administration (HRSA) contributed to the initiative.


National DNA Day commemorates the completion of the Human Genome Project and the discovery of DNA's double helix in 1953. In its third year, the celebration includes an Ambassador program, in which NHGRI investigators, pre- and post-doctoral fellows and staff travel to high schools around the country to excite students about the field of genomics. This year, there will be a focus on establishing relationships with outreach schools. There will also be a webcast featuring NHGRI intramural researchers lecturing to high school students, and a chatroom with students. NHGRI will also hold a conference in March to provide a group of teachers in the Washington D.C. area with DNA Day resources and information. NHGRI partners with the American Society of Human Genetics in this effort.

NHGRI - Policy

The National Academy of Sciences Committee on Intellectual Property Rights in Genomic and Protein-Related Inventions, a study funded by NHGRI, NIGMS, NCI, NIDCR and the NIH OD held an international meeting in December in Bellagio, Italy. The purpose of the meeting was to learn more about how European and Japanese governments handle IP issues related to genetic and proteomic inventions. Tim Leshan, Chief of the Policy and Program Analysis Branch, attended the meeting as the NIH liaison. The meeting focused heavily on science, and the impact of patenting on protein research and genomics was detailed.

The FY 2005 Labor Health & Human Services and Education Appropriations bill, which includes NIH funding, was incorporated in an omnibus appropriations bill that was finally passed in December. The conference agreement appropriates $28.371 billion for NIH, an increase of $571 million (2.1%) over the FY 2004 level. The increase was offset in part by an across-the-board cut of 0.80 percent in all non-defense and non-homeland security spending. The NHGRI received $492 million minus the 0.8% cut for a total of $488 million. The President will present his FY 06 budget today. It is expected to be a flat budget for domestic discretionary programs, and the Congress is expected to concur.

There are now two new Appropriations Committee Chairmen, Senator Thad Cochran (R-MS) and Representative Jerald Lewis (R-CA). Both have said they want to pass the appropriations bills as soon as possible after the passage of the budget resolution. The Labor HHS Appropriations subcommittee chairmen, Senator Arlen Specter (R-PA) and Representative Ralph Regula (R-OH), will remain in place.

The Genetic Information Nondiscrimination Act of 2003 (S. 1053), passed by the Senate, was not taken up in the House last year. The Subcommittee on Employer and Employee Relations of the Committee on Education and the Workforce held a hearing on the subject, as well as the Secretary's Advisory Committee on Genetics Health and Society (SACGHS). The SACGHS will follow-up with a report to Mike Leavitt, the new Secretary of HHS, on the subject. This issue remains a priority for NHGRI and we will continue to work on it with the new Congress. The new Chairman of the Senate Committee on Health, Education, Labor and Pensions (HELP), Michael Enzi (R-WY), has put S. 1053 back on the committee's agenda. He would like to pass the same bill early in the session and it will be marked up in committee this week. In the House, objections have been raised by the insurance industry and the Chamber of Commerce.

The Secretary's Advisory Committee on Genetics, Health and Society (SACGHS) held its fifth meeting October 18th-19th, 2005. Discussions included the importance of family history in health, coverage and reimbursement, and a discussion of plans for addressing large population studies and pharmacogenomics. The committee also heard testimony about and discussed the issue of genetic discrimination. Its next meeting is Feb. 28 - March 1, 2005. The possibility of a U.S.-based large population study will be discussed at that next meeting. While a U.S. study of this type has not yet received funding, there are ongoing analogous efforts in the U.K. (BioBank), Japan, and Estonia.

Centers of Excellence in Genomic Sciences (CEGS)

The Centers of Excellence in Genomic Sciences (CEGS) program was formulated in 2000 and 2001 to identify promote new areas of innovative genomics research. This preceded the planning process for the 2003 Vision statement. CEGS grants are intended to be for highly innovative efforts to develop new concepts, methods, technologies, or ways to analyze data, and to advance the state of the art for investigating genomic approaches to biological problems in a substantial way. Tightly focused teams, synergy, and integration are key for this program, as is training to increase the pool of professional genomics scientists and engineers, and to ameliorate the shortage of genomics professionals from underrepresented minority communities.

The CEGS program announcement (PA) was released in 2000. To date, forty-one P50 (center) grant applications have been received and six P20 (planning grant) applications have been received, but none have been funded. Nine CEGS awards have been made, and information about the centers is available on the NHGRI website. NIMH, which joined the original program announcement, has co-funded two CEGS; one to Johns Hopkins University and one to Columbia University.

The CEGS PA has since expired. NHGRI has been conducting a variety of assessments as part of its consideration of the program's future, including administrative site visits to the first three CEGS that were funded (specifics of which will be discussed in the Closed Session). The discussions have focused on CEGS program quality, program consistency with the NHGRI Vision statement of 2003, program objectives consistent with NHGRI objectives, and priority in the NHGRI portfolio. Staff has concluded that CEGS have increased the visibility of genomics at institutions, created genomic infrastructure and training opportunities, assembled good groups of scientists, and approached problems that have been inaccessible through traditional grant mechanisms. This is a mechanism to accomplish things that could not be done with standard grants. The subject was put on the agenda of this meeting to afford Council an opportunity to review Staff's findings and conclusions.

In a lively discussion, Council members made a number of points about the CEGS program and the CEGS grants:

  • The CEGS program echoes the goals of the Roadmap by creating interdisciplinary research; it may take several years to gauge the success of the centers, as they take a long time to get going.
  • The CEGS are productive, innovative projects that take us in new directions that would have been difficult without the mechanism.
  • CEGS drive technology, with the emphasis on leveraging technology to create new abilities and bringing projects together to achieve greater things than normal grants can achieve.
  • CEGS have stimulated the use of genomic information by people that would normally not be working in the area, e.g. engineers have been brought into biology.
  • It can be a challenge for the CEGS to keep up with their success, and it is difficult to gauge progress in the CEGS program.
  • A high level of innovation must be maintained for researchers to join the CEGS program. This criterion will ensure that the funding level of the program doesn't exceed $30 million.
  • The CEGS can bring minorities into genomics research in new and important ways.
  • CEGS provide a critical investment in new technology. There is a high price tag for the program because the CEGS are a long-term investment and long-term follow-through with the individual grants is required.
  • There is synergism between and among the CEGS, and they are talking and learning from one another. The grantee meetings aid in collaborations between the CEGS.
  • The second grantee meeting showed considerable progress when compared to the first meeting.

Council members also noted a number of issues for Staff to consider in developing the CEGS program further:

  • The site visits have been focusing upon where the centers are in their development and whether or not they are still on the cutting edge of the research, recognizing that the CEGS program was designed to support centers for up to 10 years.
  • Some CEGS might lose their innovative position or innovation might come in smaller steps; these CEGS might need to be eliminated if they cannot keep up.
  • Technology distribution is also important.
  • There are surely new technologies and new efforts that can benefit from the CEGS approach; the portfolio might need to be balanced further.
  • It is not sufficient for a CEGS merely to stay on the track that was laid out at the beginning of the award. Something that was very innovative when a grant was written may not be innovative today.
  • Some of the centers might eventually switch to a focus on data collection, but in doing so would become something other than a CEGS.
  • NHGRI should continue to explore the development of new mechanisms to support specific Institute objectives other than the R01.

In summary, the general consensus of the council was that the CEGS program should be continued. At the May and September Council meetings, there will be broader discussion of funding the CEGS program in the context of other NHGRI initiatives.

Minority Action Plan (MAP)

The main goal of the NHGRI's Minority Action Plan (MAP) is to increase the number of underrepresented minority investigators in scientific and ELSI research. The MAP opportunities have been incorporated into all of NHGRI programs, including those in the DER, DIR, and OD, and must be available at all career levels. Programs must be anchored in institutions involved in genomics and ELSI research, have achievable goals, and undergo review. There are several components, including research training, research collaborations, education, outreach, communications, and partnerships with other institutes.

The MAP was begun in 2001, when Council approved the plan. With respect to the DER component, the first supplement requests were received in March 2002, and the first awards were made in September of that year.

MAP program requirements have been tailored for different types of grants. Training grants are required to have 10% of trainees from Underrepresented Minorities (URM) within the next 3 years. CEGS are also required to have 10% URM. The data production centers and databases are encouraged to recruit, foster, and guide employees to enhance their research careers, starting at the technician level.

In the overall DER MAP, supported activities range from K-12 to faculty-level programs. Many of the activities are focused on undergraduates. The total investment is currently $4.7 million. There are currently 11 active T32 NHGRI training grants. The numbers of URM are increasing, and we are working with those T32 grants that are not faring as well. According to a recent review by the MAP Advisors, 50% of programs have been successfully implemented, 20% are doing fine but need monitoring, and 20% need to be closely monitored.

A number of lessons have already been learned, as described at a MAP grantees meeting last fall and summarized by the MAP Advisors:

  • Grantees should recruit within their own institutions.
  • Students should be taught to network and encouraged to recruit friends. To facilitate networking, an MAP web site should be constructed.
  • A coordinating center could also help to facilitate networking, tracking, and program evaluation.
  • The number of undergraduate students, graduate students, and postdoctoral fellows should be increased.
  • NHGRI should better articulate the expected goals and outcomes to grantees. Evaluation is an important component of the MAP. Evaluation plans for individual programs and the overall MAP program should be developed and implemented.
  • The level of MAP participation appropriate for non-academic institutions should be reconsidered. Many non-academic institutions lack the infrastructure necessary for these efforts.

In the ensuing discussion, the Council members made a number of points:

  • The Council is pleased with the progress of the Minority Action Plan to date.
  • There was some concern about the relative distribution of the current investment in the K-12 arena. On one hand, the earlier we begin to expose people to genomics in the MAP program, the greater the likelihood of keeping a portion of them in the pipeline as they get older. On the other hand, there are problems when centers only have a K-12 effort.
  • More emphasis should be placed on undergraduates and the transitions between undergraduate and graduate school and between graduate school and postdoctoral training.
  • NHGRI should not go overboard in either direction. The MAP should have both K-12 efforts and later efforts. NHGRI needs to be smarter about the way in which the K-12 programs are operated, rather than eliminating them. We should build on existing programs in math and science.
  • The coordinating center is important, but it is expensive to engage in this effort correctly.
  • The NHGRI's goal of doubling the number of minority investigators in the next five years will be difficult to achieve but important. Each of the centers is currently dealing with small numbers and there was some concern about a quota-driven approach to these programs, rather than a best career-based approach.
  • An overriding vision is critical for following through with the program the plan to incorporate the CEERs into the MAP will be very helpful, and will increase the numbers of URM considerably. ELSI is a critical part of genomics, and even though these researchers are not going into the laboratory for basic science work, they are still an important to the field.
  • There are often geographical areas that are difficult to reach.
  • Basic and clinical sciences need more mutual understanding. The connection to the medical profession is useful for enticing interest in genomics.
  • Outreach to distant minority communities could be accomplished through DNA day activities, whether they are through ambassadors or grantee institutions (see above). Other NIH institutes have responsibilities in the area of minority involvement as well.

ELSI Research Advisors (ERA) Report

Eric Juengst presented a report on the recent ELSI Research Advisors (ERA) meeting. ERA is a subcommittee of Council; there is an ERA evaluation and report every five years.

The ELSI program has revised its Program Announcements to incorporate issues relevant to the Vision statement of 2003. Much of ELSI funding is now going into the "Genomes to Health" arena that looks at medical issues. There are perennial ELSI challenges, including expansion of ELSI disciplines and researchers, integration between ELSI research and genomic laboratory research, and more effective translation of ELSI research findings to products that can inform policy deliberations.

The Centers of Excellence in ELSI Research (CEER) program has been developed to address a number of ELSI program goals, and there are CEERs that are addressing research issues in each floor of the Vision. CEERs can build communities, increase efforts in training and outreach, and translate research into policy. All of the CEERs have minority outreach training programs. However, CEERs cannot replace the investigator-initiated grant portfolio, or accomplish their own goals without additional grants for collaborative research, trainee research opportunities, and collective evidence-based policy initiatives.

The issue of the difference between the scope of ELSI research and the funds available in NHGRI to support that area of research was discussed by ERA. Members noted that the research programs of many other NIH institutes can benefit from genomic approaches and ELSI research, and ideally NHGRI would not be the only, or even primary source, of funds. In reality, however, while many other institutes have signed onto the ELSI Program Announcement, the relative amounts of NHGRI and non-NHGRI funding are not proportionate. In ERA's opinion, there is an NIH-wide need for ELSI programs, but there are currently not resources to develop these programs in other institutes. ERA discussed several ways to encourage this at the NIH.

Council concurred with the importance of incorporating ELSI research and bioethics research into science across the NIH. Unfortunately, members noted that the fact that R01 funding rates are dropping precipitously in this tight funding climate does not encourage such a new investment. Council asked whether the NIH Roadmap could be a vehicle for a specific trans-NIH ELSI initiative. One interesting theme could be the ELSI issues surrounding the development of a predictive and preventive medicine. IRB consistency is another important topic. Investment in this area could make translational research much smoother. Dr. Collins noted that harmonizing translational research protocols was originally suggested as a Roadmap Initiative in 2003.


The budget tables for FY 2004, 2005, and 2006 were distributed. The proposed FY 2006 budget has an increase of 0.5%, which is the smallest in many years. Any budgetary increase from year to year must encompass the traditional 3% increase per year in an award's budget. Previously funded grants need to be funded at full levels as well. The House and the Senate will now take up the proposed President's budget. Over the next few years, the NIH will likely have budget figures that do not keep up with inflation.

NIH Roadmap Status Report

The NIH Roadmap is a cross-institute effort to fund broad initiatives that do not fit within the purview of a specific institute. Accelerating research and eliminating roadblocks are important to the Roadmap. New Pathways to Discovery, Research Teams of the Future, and Re-engineering the Clinical Research Enterprise are the three themes of the Roadmap. NHGRI is mainly involved in the New Pathways to Discovery theme, and is particularly involved in the Molecular Libraries and Imaging, Nanomedicine, Computational Biology, and Building Blocks, Biological Pathways and Networks Initiatives.

Within the Molecular Libraries and Imaging Initiative (MLII), the NIH Chemical Genomics Center (NCGC) has been implemented within the NHGRI's Division of Intramural Research. The larger high-throughput screening program will comprise the Molecular Libraries Screening Centers Network (MLSCN), in which the NCGC will participate. The extramural components of the MLSCN will consist of pilot screening centers, which be funded later in FY2005, after review by the NIMH Council. The MLSCN program will be co-managed by NHGRI and NIMH. Other components of the Network will include a new database at NCBI, called PubChem, where the screening centers will deposit their data and which will also contain the chemical structure of small organic molecules and information on their biological activities, and a compound repository. Two other grant programs in the Molecular Libraries Initiative are being managed by NHGRI and will require second-level review by the Council in August. Specifics on the early concurrence process will be provided at the May Council meeting.

In other Roadmap initiatives of interest to NHGRI, four National Centers for Biomedical Computing have been funded. The Nanomedicine Initiative has funded concept development for centers, and center awards will be made at the end of FY 2005. NHGRI is also involved in the Building Blocks, Pathways, and Networks Initiative and the Pioneer Awards. Re-engineering the Clinical Research Enterprise is another major Roadmap activity and is designed to support the NIH's aims to improve the process of taking science from bench to bedside to practice.

Overall, Roadmap efforts have brought staff together from many different institutes to work closely to plan and manage these initiatives. The initial set of Roadmap initiatives will be reviewed by the Institute and Center (IC) Directors at an upcoming retreat, and the possibility of developing a set of new initiatives will be discussed. However, as the NIH is experiencing such a budget crunch, institutes may not feel comfortable with expanding their contribution to Roadmap funds. The Roadmap Initiative, averaged over six years, is about 0.9% of the total NIH budget. More information on the NIH Roadmap can be found at

HapMap Update

The first phase of the HapMap, which will be completed by the end of February, has involved genotyping 1 million SNPs across the human genome, or on average, one SNP every 5 kb across the genome. Genotyping in the CEPH samples is the most complete at this time, since they were the first available, but the genotyping of the three additional populations is rapidly being completed.

The second phase of the HapMap will involve 4.7 million attempted SNPs. The HapMap pipeline will use SNPs discovered in the ENCODE regions, as well as SNPs discovered in the MGC project. The Phase II genotypes will be done by July 2005, and the second phase of the HapMap will be completed in October 2005. The total of approximately 5 million SNPs expected to work across the genome will produce a better HapMap and enable discovery of SNPs in linkage disequilibrium (LD) with other SNPs, including SNPs involved in diseases. This will result in a good selection of tag SNPs for use in research. Most common SNPs and many rare SNPs will be in databases, which will enable research on numerous diseases.

The third phase of the HapMap will involve looking at samples from additional populations beyond the initial four, in the HapMap ENCODE regions, to examine how applicable the HapMap is to other populations.
Overall, Council was impressed by how well the HapMap has progressed, and its user-friendly interface.

Mammalian Gene Collection (MGC) Update

The MGC is a multi-institute effort to produce high-quality cDNA sequences with the full Open Reading Frame (ORF) for all human and mouse genes, and for a set of 6,250 rat genes . The MGC pipeline is also used to develop Xenopus and zebrafish collections. All MGC data and materials are publicly available.

The MGC is approximately 53% complete for human, with 12,237 non-redundant full-ORFs, and 48% complete for mouse with 11,151 non-redundant full-ORFs. The EST-based strategy for identifying MGC clones reached a point of decreasing yield for both human and mouse last year. As a result, new strategies have been initiated for the completion of the human and mouse clone collections. This primary new strategy involves PCR-rescue of clones that have well-known RNA structure and function, or known structure but no known function. PCR-rescue of predicted genes has also been initiated. Contracts have been awarded to Baylor College of Medicine and British Columbia Genome Sequencing Center to start PCR rescue programs. 60% recovery of genes is expected during the first two contract years. Current PCR rescue efforts are slightly behind schedule, but the centers have ramped up so that they can meet the first-year goals by the end of the initial contract year.

For the testing of prediction-based strategies, contracts have been awarded to Washington University in St. Louis and the University of California Santa Cruz (UCSC). Exoniphy, with EST support, and Twinscan, without EST support, are the algorithms that are being used for this effort. Coordination with the ENCODE program has been initiated. So far, the success rate is approximately 60-70% for predictions with EST support, and 15% for those without EST support.

Other possible strategies for obtaining currently missing genes include synthesis of full-ORF genes, purchasing full-ORF genes from private collections, exchanging full-ORF genes with other public collections, and advertising to the research community for genes that they could provide to the collection.

Another potential future program being considered involves converting the human MGC clones to an expression-ready format. This would allow the use of MGC clones for large-scale proteomics, permit N- and C- terminal tags, and eliminate the PCR step usually necessary for putting the clones into expression vectors. Issues being addressed include the vector to used, how to build on existing expression-ready collections, whether to include stop codons (the so-called closed format) or not (the open format), the effect of an expression-ready format on cost and timelines of PCR rescue, and funding considerations for this program.

Council members asked about:

  • Overlap with the RIKEN clone collection, as MGC could save time and money if those clones were available.
    • Staff will investigate whether or not there are still intellectual property concerns with their clones.
  • Plans to extend the clones through the 5' UTR.
    • There are no such plans at this time; the amount of money that is currently allocated in R01 grants for converting clones into expression-ready formats. Consolidation of these funds could be an efficient way to create an expression-ready collection.

The Encyclopedia of DNA Elements (ENCODE) Project Update

The Encyclopedia of DNA Elements (ENCODE) project is being approached in a phased approach. There is an ongoing pilot project that targets 1% (30 Mb) of the human genome, as well as a technology development effort. The goals of the pilot project are to test and compare existing experimental and computational methods for analyzing of the human genome. The ENCODE website is A project description paper was published in 2004.

DNAse hypersensitive sites, long-range regulatory elements, cis-regulatory elements, and other targets are being examined using numerous techniques. To inform the human ENCODE regions, the orthologous regions from numerous other organisms are being sequenced to a comparative-grade finish. The ENCODE Consortium holds regular meetings and teleconferences.

Data from the ENCODE project are stored in public databases. The sequence-based data are displayed on the UCSC genome browser. The NHGRI intramural program is developing a portal for accessing the non-sequence-based ENCODE data.

Overall, data release has gone smoothly. Data verification and data standards are being implemented, although much of the data is in different formats. Dr. Myers, who is a member of the ENCODE Consortium, commented that it has been difficult for groups to adapt to the program's data release policy; some groups have been concerned about data quality. He is confident, however, that any problems that have been encountered can be solved and that data will be released expeditiously.

Dr. Eddy asked about the timeframe for expanding ENCODE to the rest of the genome. Expansion could happen as soon as one year from now, but the plans for doing so are under active discussion within the Consortium and with the program's External Scientific Committee (ESC). The establishment of quality control and finishing criteria will be prerequisites to scaling up.

Concept Clearance for an ENCODE Project for Model Organisms

Dr. Feingold presented a new initiative to undertake an ENCODE-like project for one or more well-studied model organisms, in order to accomplish the following aims: to coordinate research on genome function for these organisms; to complement the current human ENCODE pilot project; and to help inform methods for scaling ENCODE to the entire human genome.

Council has previously encouraged NHGRI initiate a parallel project to ENCODE (modENCODE) to find all functional sequence elements in the entire genome of one or more model organisms. The concept presented at this meeting proposed to consider analysis only of very well-studied model organisms with strong functional genomics communities, specifically S. cerevisiae, C. elegans and D. melanogaster. NHGRI has encouraged each of the three communities to discuss the capabilities and advantages of each model system for a potential modENCODE effort. As a result, white papers will be submitted this spring. After reviewing these, staff will evaluate whether there is a need for a small, focused workshop to help guide the NHGRI's decisions about the goals of the modENCODE initiative. It is not yet known whether NHGRI could afford to do a modENCODE project for all three organisms, or just one. The scope of modENCODE would be somewhat broader than that of the human ENCODE pilot phase. For example, modENCODE would address the entire genome of the target organism(s).

Each group will develop, by this spring, a white paper outlining their conclusions.

The concept clearance proposed that mechanism of support would be the cooperative agreement, although it remains to be decided whether a single, omnibus application will be sought from each community or whether individual R01 or R21-scale applications will be solicited and coordinated upon funding. Additional mechanisms may be used to support other activities necessary to meet the needs of this project, such as the development and distribution of common reagent sets and a centralized database.

Dr. Myers mentioned that much work in this area has already been done on yeast. This would potentially decrease the costs needed for a yeast modENCODE project. Dr. Eddy noted his preference for smaller projects instead of an omnibus proposal, to encourage more of the community to be involved. Dr. Gelbart said that there might be an intermediate ground. The Council approved the concept as presented.

Memorandum of Understanding

The statement of understanding between NHGRI staff and the NACHGR was amended based on previous Council discussion and re-presented to the Council. The Council had been concerned that the staff administrative authorities originally proposed might be too large for some large grants, such as sequencing centers. Therefore, staff suggested that a cap of 1 million dollars be added to the 25% authority. Expedited Council approval for administrative actions was also included in the memorandum. A summary of expedited actions will be distributed to Council after Council has approved the actions.

Council approved the revised Memorandum of Understanding.

2005 Biennial Advisory Council Report on Population Tracking

Every two years, the NIH requires a presentation to Council of how well NHGRI has tracked women and minority participants in clinical research. Clinical research includes patient-oriented research, epidemiological and behavior studies, outcomes research, and health services research. NIH has developed a population tracking database, and program directors must examine enrollment data for proposed studies to see if it complies. The NACHGR must prepare a report on the inclusion of women and minorities in clinical research. Most of the NHGRI-funded clinical research is housed in the ELSI program, as NHGRI does not fund clinical trials. Issues with the inclusion of women and minorities must be addressed and corrected before a grant application can be reviewed and funded. Enrollment data for clinical research is based on what is called for in the protocol.

Dr. Murray pointed out that aggregate data might not accurately reflect the inclusion of woman and minorities in specific projects. Program Directors must be aware of inclusion statistics on a case by case basis.

Dr. Gaines said that if all of the protocols do not have the same requirement in terms of the groups enrolled, then we are potentially not inclusive or fair overall. The review groups examine the applications to see if the groups enrolled are scientifically warranted; if they are not, then the priority score must be decreased to reflect this problem.

Some clinical projects in the NHGRI ELSI program exclusively include minorities, but none would exclusively include Caucasians. NHGRI Program Directors make sure that the investigators recruit the woman and minorities that have been specified in the grant application. Overall, women are more likely to volunteer to participate in genetic research. The NIH does not require tracking of participation in non-clinical, biomedical research as of yet.

Council-Initiated Discussion

Last council, Mary Hendrix mentioned that she would like to hear a discussion of epigenetics and NHGRI's involvement in this area. There is interest in inviting Dr. Feinberg (JHU) to speak at the May Council meeting.

There will also be a discussion of the NHGRI budget at the May Council meeting.

Dr. Weinstock mentioned that since so many genomes are being sequenced, the research community is asking if there will be a resource for having particular tiling path clone sets available. There is currently a gap between where the large clone sets lie and making tiling paths available to the public. Dr. Myers said that there is potential interest in the biotechnology sector. Paying for the tiling path and the freezers is a concern of industry, although there is industrial interest in clone distribution. Dr. Patrinos has raised this issue in regard to Joint Genome Institute projects. NHGRI staff will investigate this topic. NHGRI can take leadership in this area, but since NHGRI has already paid for development of the tiling path, there was concern expressed about committing additional funds.

Announcements and Items of Interest

Dr. Guyer noted two items of interest in the Council folders, including a report from the National Society of Genetic Counselors on their activities and a report on a workshop held to discuss long-term maintenance of genome sequence assemblies. The workshop discussed the importance of strict data deposition standards at the trace repository, as well as strict data quality standards.

Conflict of Interest

Dr. Guyer read the Conflict of Interest policy to Council and asked them to sign the forms provided.

Review of Applications

In closed session, the Council reviewed 117 applications, requesting $41,137,929. The applications included 57 regular research grants, 12 pilot projects, one program project, 13 ELSI grants, two area grants, three center grants, three conference grants, one research career development award, two training grants, 11 SBIR Phase I grants, five SBIR Phase II grants, two fellowship grants, three STTR Phase I grants and two others. A total of 70 applications totaling $31,897,135 were recommended.

I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.

__________________ ______________________________________________
Date Mark Guyer, Ph.D.
Executive Secretary
National Advisory Council for Human Genome Research

__________________ ______________________________________________
Date Francis S. Collins, M.D., Ph.D.
National Advisory Council for Human Genome Research

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Last Reviewed: March 23, 2012