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National Advisory Council for Human Genome Research
Summary of Meeting

Bethesda, Md.

February 10-11, 2003

The National Advisory Council for Human Genome Research was convened for its thirty-seventh meeting at 8:30 a.m. on February 10, 2003, at the Natcher Conference Center, Bethesda, MD. Francis Collins, Director of the National Human Genome Research Institute, called the meeting to order.

The meeting was open to the public from 8:30 a.m. until 3:00 p.m. on February 10, 2003. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 3:15 p.m. on February 10 until adjournment on February 11 for the review, discussion, and evaluation of grant applications.

Council Members Present

Vickie Yates Brown
David R. Burgess
Wylie Burke
Ronald W. Davis
William M. Gelbart
Eric Juengst
Bronya J. Keats
Richard P. Lifton
Kim Nickerson
Maynard V. Olson
Janet D. Rowley
Robert H. Waterston
vTadataka Yamada

Ad Hoc Members Present:

Beverly Gaines
Janis Hutchinson
George Weinstock

Ex Officio Members Present:

Gerard Schellenberg

Council Members Absent:

Raju Kucherlapati
Robert Tepper

Staff from the National Human Genome Research Institute:

Chris Austin, OD
Maggie Bartlett, OD
Vence Bonham, OD
Joy Boyer, DER
Lisa Brooks, DER
Jean Cahill, DER
Monika Christman, DER
Francis S. Collins, OD
Elise Feingold, DER
Adam Felsenfeld, DER
Barbara Fuller, OD
Mary Glynn, OD
Peter Good, DER
Bettie Graham, DER
Eric Green, DIR
Alan Guttmacher, OD
Mark Guyer, DER
Karen Hajos, OD
Linda Hall, DER
Linda Jacobson, OD
Sandra Kamholz, DER
Ron King, DIR
Rebecca Kolberg, OD
Tim Leshan, OD
Emily Linde, DER
Elliott Margulies, DIR
Jean McEwen, DER
Rodecia McKnight, DER
Ken Nakamura, DER
Ken Ow, OD
Diane Patterson, DER
Allison Peck, DER
Jane Peterson, DER
Rudy Pozzatti, DER
Daryl Pritchard, DIR
Jerry Roberts, DER
Pamela Sellman, DER
Jeff Schloss, DER
Erin Shannon, OD
Larry Thompson, OD
Elizabeth Thomson, DER
Kris Wetterstrand, DER
Lynn Zacharia, DER
Judith Wyatt, OD
Susan Vasquez, OD

Others Present for All or a Portion of the Meeting:

Joann A. Boughman, American Society of Human Genetics
Cheryl Corsaro, CSR
Leland Ellis, U.S. Department of Agriculture/ Agriculture Research Service
Edward Kloza, National Society of Genetic Counselors, Inc.
John Norvell, NIGMS
Sharon Olsen, International Society of Nurses in Genetics, Inc.
Ari Patrinos, U.S. Department of Energy
Angela Sharpe, Consortium of Social Science Associations
Michael Watson, American College of Medical Genetics
Elias Zerhouni, NIH

Introduction of Liaisons and New Employees

Dr. Mark Guyer welcomed three ad hoc council members, Beverly Gaines, Janis Hutchinson, and George Weinstock. Dr. Guyer welcomed the professional society liaisons: Edward Kloza, the representative of the National Society of Genetic Counselors; Sharon Olsen, the representative of the International Society of Nurses in Genetics; and Michael Watson, the representative of the American College of Medical Genetics. Dr. Guyer also welcomed Leland Ellis from the Department of Agriculture and Ari Patrinos from the Department of Energy.

Approval of Minutes

The minutes from the September 9-10, 2002 Council meeting were approved as submitted.

Future Meeting Dates

The following dates were proposed for future meetings:

May 19-20, 2003 May 10-11, 2004
September 15-16, 2003 September 13-14, 2004
February 9-10, 2004 February 7-8, 2005

Director's Report

I. General Announcements

Council member, Robert Tepper has been promoted to President, Research and Development at Millennium Pharmaceuticals, Inc.

Sydney Brenner, John Sulston and former Council member Robert Horvitz, were awarded the Nobel Prize in Physiology and Medicine.

Robert Nussbaum has been elected as president of the American Society of Human Genetics.

Dr. Collins attended the World Economic Forum annual meeting in Davos, Switzerland and participated as the discussion leader on various topics.

Personnel Changes: Division of Intramural Research: Eric Green, formerly the chief of the Genome Technology Branch, has been selected as the new scientific director.

Office of the Director: Jean Jenkins has been appointed as the Senior Clinical Advisor; she will be involved in the education projects, including education of health professionals and the public about the role of genetic medicine in the clinic. Christopher Austin has been appointed as the Senior Advisor to the Director for Translational Research.

Ting-Kai Li was appointed the new Director of the National Institute on Alcohol Abuse and Alcoholism. Thomas Insel was appointed the new Director of the National Institute of Mental Health. Nora Volkow was appointed the new Director of the National Institute on Drug Abuse.

II. Recent Scientific Accomplishments
Genome Sequencing Updates

Human: The sequencing centers are on track to finish the human sequence to the prescribed standards by April2003. A more detailed update on finishing the human genome sequence was presented to the Council in closed session.

Mouse: The Mouse Genome Sequencing Consortium, under the leadership of Eric Lander and Bob Waterston, published an assembly and a first analysis of the mouse sequence in the December 5, 2002 issue of Nature. Perhaps the most intriguing finding was that more than half of the conserved sequence between human and mouse is of unknown function.

Rat: On November 25, 2002, the Rat Genome Sequencing Consortium announced assembly of the DNA sequence of the rat genome. The assembly used 33 million reads, which were combined with whole-genome shotgun sequences, for a total of 6.5-fold coverage.

Chicken: The Washington University Genome Sequencing Center has begun sequencing the genome of the chicken, Gallus gallus. As of 1/31/03, 661,508 traces were available in the Trace Repository.

Chimp: The Washington University Genome Sequencing Center and the Whitehead Institute for Biomedical Research, in collaboration with Japanese and German colleagues have begun sequencing of the chimpanzee, Pan troglodytes. The Chimp Consortium met at Marco Island earlier in February to discuss progress.

Honey Bee: The Baylor College of Medicine Human Genome Sequencing Center has begun the sequencing of the honey bee, Apis mellifera. The honey bee is used in behavioral studies. The sequence will also be useful for comparison with the Drosophila sequence.

Dr. Collins referred news releases about additional model organisms (Tab L of the handout material). The cow and dog were added to the high priority list for sequencing.

III. Extramural Program

HapMap: The International HapMap Project was launched on October 29, 2002. The consortium includes laboratories and agencies in Japan, United Kingdom, Canada, China, the United States, and The SNP Consortium. The total budget for the project is approximately 100 million dollars.

The genotyping will be done in a regionalized fashion, using samples from populations originating in Africa, Asia and Europe. . The European samples have been obtained from the CEPH collection; all have been reconsented for use in the HapMap Project and the first plates are being distributed to the genotyping centers. Community engagement and sample collection are ongoing in Japan, China, and Africa.

Dr. Collins thanked NHGRI Program Directors, Lisa Brooks and Jean McEwen, for their ongoing efforts in organizing the project

UniProt: NHGRI has awarded a grant, co-funded with five other NIH Institutes, to combine the three current protein sequence databases to form the United Protein Database (UniProt).

ENCODE: NHGRI is organizing a new research consortium, the Encyclopedia of DNA Elements (ENCODE), to identify all functional elements in human DNA. The effort will begin with a pilot project focused on 1 percent (30 Mb) of the human genome. In addition, NHGRI will also support the development of new and improved technologies to meet the goals of the project. Two RFAs were released: "Determination of All Functional elements in Human DNA" and "Technologies to Find Functional Elements in Genomic DNA."

MGC: The Mammalian Gene Collection (MGC) published a paper in the December 2002 issue of PNAS describing the status of the project. The goal is to sequence and make available a full-ORF set of clones representing each gene of both the human and mouse genomes. The External Steering Committee met and discussed changes in the current strategy needed to reach completion of mouse and human collections; the ESC recommended that the project adopt a more directed approached as the current random cDNA library strategy appears to have reached the point of seriously diminishing returns. This project has support from about a dozen NIH institutes. At the meeting, the ESC also considered taking on additional organisms such as zebrafish, xenopus, or the rat. The priorities for more organisms may be addressed by using a white paper process.

IV. Policy Issues

Appropriations: Congress has not passed the FY03 Appropriations and the NIH is still operating under a continuing resolution. The NIH is hopeful Congress will complete the effort to double the NIH budget over five years. The FY04 budget was unveiled by the President last week. The NIH would receive a 2 percent increase, which would be equivalent to a 4 to 4.5 percent increase in funds available for research.

Genetic Discrimination: Senator Judd Gregg, the new chairman of the Senate Health, Education, Labor, and Pensions Committee hopes to consider a genetic anti-discrimination bill in March.

IRB Guidebook: NHGRI staff have been asked to prepare an up-to-date description of human subjects protection issues in genetics research for submission to the Department of Energy-led revision of the IRB guidebook. This document was most recently revised 10 years ago.

Advisory Committee Updates: The Secretary's Advisory Committee on Genetic Testing has been replaced by the Secretary's Advisory Committee on Genetics, Health, and Society, chaired by Ed McCabe. The group consists of 13 doctors, scientists, and other experts.

The Secretary's Advisory Committee on Human Research Protection (SACHRP): This committee will be chaired by Ernest Prentice and focus on the review of research with embryos, fetuses and pregnant women, and other special populations.

President's Bioethics Council: Dr. Collins was invited to speak on December 13 to the President's Bioethics Council regarding the issue of genetic enhancement. NACHGR member, Janet Rowley is also a member of the Council. The Council has published a report on its deliberations regarding cloning and is looking at a number of issues to investigate further. These include transplantation, payment of organ donors, records in IVF clinics for the proportion of successes and failures, and the management and storage of embryos in these clinics.

V. NHGRI - Education and Outreach

NCHPEG: The National Coalition for Health Professional Education in Genetics (NCHPEG) met jointly with GROW (Genetic Resources on the Web)on January 29-31. This is funded by HRSA and focuses on the genetic literacy among health care professionals.

Report from the Department of Energy (DOE)

Ari Patrinos discussed genome research activities at the U.S. Department of Energy (DOE). Eddy Rubin was selected as director of Joint Genome Institute (JGI). Nora Volkov, who has been selected as the director for NIDA, is a member of the DOE's Biological and Energy Research Advisory Committee (BERAC).

Updating the status of the human genome sequencing efforts at the JGI, Dr. Patrinos reported that chromosome 19 is finished with 3-4 gaps, chromosome 5 has 6 remaining gaps, and chromosome 16 is 95 percent completed with 11 gaps remaining.

The "Genomes to Life" program is sponsoring a workshop in Crystal City to share pre-publication data. The DOE has received 260 letters of intent for the program. In the area of computational biology, representatives from the DOE are traveling to Japan to visit their Earth simulator computer and discuss potential applications.

With respect to microbial genomes, the DOE is planning annotation jamborees. Dr. Patrinos expressed his excitement to be involved with the upcoming April 2003 events.

Pre-Publication Data Release

The Wellcome Trust sponsored a meeting on January 14-15, 2003 in Ft. Lauderdale, FL to discuss how pre-publication data release of large-scale genomic data can promote the best interests of science and help to maximize the public benefit gained from research. About forty people attended, including sequence producers, users, and representatives from journals, databases, and funding agencies. Dr. Guyer distributed the report from the meeting along with a draft of an NHGRI policy statement entitled, "Reaffirmation and Extension of NHGRI Rapid Data Release Policies: Large-scale Sequencing and Other Community Resource Projects".

In 1996, the International Human Sequencing Consortium proposed that the Human Genome Project operate under a practice of rapid data release, the so-called "Bermuda Principles". All funding agencies participating in the project accepted that recommendation. Since that time, there have been a number of developments with respect to the generation of large-scale sequence data and the application of the rapid data release policy. There are new types of sequence data that were not anticipated at the time of the Bermuda meetings (e.g., whole genome assemblies and raw traces) and thus not taken into account under the data release guidelines. Therefore, the attendees of the meeting enthusiastically reaffirmed the "Bermuda Principles" for rapid data release and recommended the practice be extended to all large-scale sequence data, including whole genome assemblies and traces.

The second recommendation generated from the meeting in Florida was that, while the producers of these data have a responsibility for releasing these community resource data rapidly and unconditionally, the data users also have a responsibility -- to respect the contribution of the data producers and to act in accordance with appropriate scientific etiquette. This will encourage the data producers to continue contribute in their mode of public benefit. The meeting recommendations also identified a third responsible party, the funding agencies which should develop appropriate policies of rapid release of sequence data and data from other community resource projects.

In a related matter, a National Research Council committee recently released a reportthat strongly advised that scientific data be released into the public domain without restriction once the paper is published. This report is on the National Academy of Sciences Web site.

Council members who attended the data release meeting agreed the topic was challenging but emphasized the importance of defining proper etiquette and educating the data users.

Ari Patrinos would like to see the community work to adopt clear policies that are standard across different agencies. He also questioned whether the policy with respect to microbial genomes should be different than for mammalian genomes. Council members were concerned about the implications for intellectual policy issues. These were discussed at the meeting in a session led by Geoff Duyk, but specific legal expertise was not represented at the meeting. Council members agreed that the community benefited from the original data release policy and generally endorsed the document but would like to see more information included about user responsibilities.

Comparative Genomics

Eric Green presented some initial results and analyses from a recently launched program to conduct comparative sequencing of targeted genomic regions from many vertebrates. The initial focus is a 1.8Mb region from human chromosome 7 containing the cystic fibrosis regulator gene and nine other genes ('the greater CFTR region'). The amount of alignable sequence between the human and 12 other species decreased with increasing evolutionary distance from the human, except for mouse and rat. This is believed to be due to the high rate of sequence evolution in rodents.

Small genomic regions were identified that are more highly conserved across multiple species. Several algorithms for identifying these "multi-species conserved sequences" were developed. The studies show that multi-species sequence comparisons can be used to identify conserved genomic regions not detectable with a single species pair. The results of this study will set the stage for understanding the functional role of these regions and pursuing new avenues of genome exploration.

NHGRI Planning Process

Dr. Collins presented the outcome of the extensive NHGRI planning process that has taken place over the past year. The plan will be published in April 2003 and has three major areas of focus: Genomics to Biology, Genomics to Health, and Genomics to Society and a number of cross cutting elements: Resources, Computational Biology, Training, Technology Development, ELSI, and Education. A subcommittee of the National Advisory Council for Human Genome Research, including Wylie Burke, Bill Gelbart, Eric Juengst, Maynard Olson, Bob Tepper, and David Valle, provided comments on the document.

The major components (Grand Challenges) in the plan are:

Genomics to Biology: Elucidating the Structure and Function of Genomics

  • Comprehensively identify the structural and functional components encoded in the human genome.
  • Elucidate the organization of genetic networks and pathways.
  • Develop a detailed understanding of the heritable variation in the human genome.
  • Understand evolutionary variation across species and the mechanisms underlying it.
  • Develop policy options that facilitate the widespread use of genome information.

Genomics to Health: Translating Genome-based Knowledge into Health Benefits

  • Develop robust strategies for identifying the genetic contributions to disease and drug response.
  • Develop ways to identify gene variants that contribute to good health and resistance to disease.
  • Develop genome-based approaches to prediction of disease susceptibility, drug response, early detection of illness, and molecular taxonomy of disease.
  • Use new understanding of genes and pathways to develop powerful new therapeutic approaches to disease.
  • Explore how genetic risk information is conveyed in clinical settings to improve health outcomes and reduce costs.
  • Develop genomics-based tools that improve the health of all.

Genomics to Society: Promoting the use of genomics to maximize benefits and non-medical settings.

  • Develop policy options regarding the uses of genomics in medical and non-medical settings.
  • Understand the relationship of genomics, race, and ethnicity, and the consequences of uncovering these relationships.
  • Access how to define the ethical boundaries of the uses of genomics.
  • Understand the consequences of uncovering the genomic contribution to human traits and behaviors.

Quantum Leaps in Technology

  • Genotyping at very low cost, allowing whole genome association studies on thousands of DNA samples for $10,000 or less.
  • Genome sequencing at $1000 or less for a mammalian genome.
  • Synthesis of any DNA molecule at high accuracy for $0.01 or less per base.
  • Determination of methylation status of all DNA in a single cell.
  • Determination of the abundance and modification state of all proteins in a single cell in a single experiment.

The Council endorsed the plan and noted the significant absence of quantifiable data collection objectives as compared to the last five-year plan. The members also noted NHGRI's attempt to play a distinctive role in translating genomics to human health, which will bring about a substantial culture change in the genome research community. The Council would like to see partnerships with other agencies emphasized in the plan. Staff asked Council to send any specific comments to them by the end of the week and they will be assimilated into the final version.

April 2003 Events

Alan Guttmacher described the several activities planned for the upcoming April 2003 celebration: "50 years of DNA: From Double Helix to Health." This will be in recognition of three historic events including the 50th anniversary of the Watson and Crick paper describing the structure of DNA, the completion of the sequence of all the human chromosomes, and the announcement of NHGRI's new research plan for genomics.

On April 14-15, there will be a scientific symposium at the Natcher Conference Center entitled "From Double Helix to Human Sequence and Beyond." The symposium will include a combination of speakers along with recorded vignettes from notable scientists involved in the Human Genome Project. There will also be a dual DVD set produced for the events with the human genome sequence and the interviews from which the vignettes were edited. On April 15, there will be a public symposium at the National Museum of Natural History entitled, "Bringing the Genome to You" with Francis Collins and James Watson speaking. April 25 will be declared National DNA Day and high schools throughout the country will celebrate using a number of tools including a videotaped session where James Watson and Francis Collins discuss genomics, and the NHGRI multimedia kit. In addition, many NHGRI scientists will be spending the day at their own high school to serve as mentors and talk about their life as a geneticist.

Month-long activities include museum exhibits, media outreach and educational events. More information about the April 2003 events is available at www.genome.gov/about/April2003

NIH Director

Elias Zerhouni thanked the members of the Advisory Council for their service to the NHGRI and spoke about his goals as Director of the NIH. He has been focused on proactively communicating how the NIH is using the increased budget to benefit the American people. As part of this challenge, he has formed a team of both extramural and intramural scientists to conduct a RoadMap exercise to focus on areas of science not attended to because they were beyond the means of any one institute. Major themes that emerged were new pathways to discovery and new problems in scale and complexity, integration biology, and more effective technologies. In addition, he has been looking at translating scientific research to health care and the roadblocks encountered in clinical research. He believes biomedical research is suffering from a lack of integration with our health care system. Furthermore, he feels the scientific team of today and that of the future are likely to be very different in the people, financial underpinnings, etc. He acknowledged that there is a higher load of technology costs and research requires the coordination of teams around core problems.

Council discussed with Dr. Zerhouni how health disparities fit into the current NIH pathways. A continuing trans-NIH priority will be the new center for Minority Health.

The members also discussed the current NIH funding mechanisms and raised questions about whether they are the most efficient way to tackle new research problems. Dr. Collins asked Dr. Zerhouni to further elaborate on his Road Map concept and the next steps in moving forward. NIH plans to ask Congress for money to fund institutes who take the lead on specific initiatives.

2003 Biennial Report on the Inclusion of Women and Minorities in Clinical Research

Mark Guyer presented the 2003 report on the inclusion of women and minorities in clinical research. This is a tracking system for extramural grants and intramural research to be sure they are setting and meeting NIH goals for the inclusion of women and minorities. There is a complication in the report because tracking and reporting methods have changed over the past two years. The numbers reported in 2003 are not equivalent to the numbers reported 1998-2000 because reporting categories have changed.

NHGRI is committed to ensuring there are representative numbers of minorities in research projects. Council requested that NHGRI set goals for enrolling minority populations in research and developing an informative tracking method.

Update on Human Sequencing

Adam Felsenfeld presented an update on the finishing of the human genome. To be defined as 'finished', 95 percent of the euchromatic region of each chromosome must be sequenced to a single base accuracy of 99.99 percent. If, after all reasonable effort, gaps remain, they must be sized and annotated. As of today, 96.8 percent of the total clones are finished. All chromosomes are at or above the 95 percent completion level. The finishing process includes chromosome coordinators, weekly Tiling Path Format (TPF) submissions, monthly gap reports, and weekly 'punchlists'. The punchlists serve as independent checks on a number of aspects of completion including questioned joins, missing mRNAs, inconsistencies vs. fosmid ends, and contaminants. As of January 15, there are 155 gaps remaining with clones available and 186 gaps without clones, of which 60 have been declared to be Type 4 (unclonable).

By April, all chromosomes will meet the operational definition of finished, missing mRNAs will be checked, all joins in the TPFs will be verified, and the detailed goals for challenging regions that remain (telomeres, centromeres, heterochromatin, segmental duplications) will be defined.

Update on the International HapMap Project

Lisa Brooks presented a summary of the Haplotype Map Project. There are five countries participating in the genotyping, 5 analysis groups funded by both NHGRI and TSC, and ongoing sample collection in China, Japan, and Africa.

The goals of this project are to develop a tool for efficient and comprehensive association studies of human disease and drug response, to find the common haplotypes in all haplotype blocks that are 10kb or larger and to find the SNPs with the variation information, for researchers to use. The populations included in the HapMap Project are CEPH, Yoruba, Japanese, and Han Chinese.

HapMap SNP Genotyping: Each group will genotype all the samples for its chromosome regions. It is estimated that roughly 1.5 million SNPs will be genotyped.

Technologies: Multiple technologies are being used including Illumina, Sequenom, ParAllele, FP-TDI, Third Wave, and Perkin Elmer.

There will be a separate project to look at the question of variation in the human haplotye map. This study will compare haplotype patterns among additional populations in about 50 regions of the genome. This project will be carried out on on a longer timetable.

Council discussed the need for additional SNPs for the project. Dr. Collins reported that both Baylor and Whitehead are each producing an additional 0.5X coverage for new SNP discovery. Washington University and Sanger Institute are also interested in helping with this effort.

Announcements and Items of Interest

Dr. Guyer noted the items of interest in the Council folders and referred Council to material under Tab T.

Council-Initiated Discussion

At their next meeting, Council would like to discuss the implementation of NHGRI's new research plan, hear a presentation from Chris Austin on chemical genomics, and discuss "dark matter".

Budget Table

Dr. Guyer referred to the Budget Table under Tab V.

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 159 applications, totaling $73,969,931. The applications included 31 regular research grants, 14 pilot projects, one program project, 53 ELSI grants, 13 center grants, two conference grants, one research career development award, three training grants, 23 SBIR Phase I, nine SBIR Phase II, one STTR Phase I, two fellowship grants, and six others. A total of 94 applications requesting $61,362,755 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

Last updated: March 23, 2012