Collection and Use of Genetic Information in the National Children’s Study Workshop  

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Last Reviewed:  6/1/2008
Last Updated:  12/21/2005

Collection and Use of Genetic Information in the National Children’s Study Workshop  

September 8, 2004
Embassy Suites at the Chevy Chase Pavilion
Washington, DC
 

Welcome and Introductions
Cynthia A. Moore, M.D., Ph.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS

Dr. Moore welcomed the participants and thanked them for participating in the workshop and for being part of the National Children’s Study (Study). She explained that the purpose of the workshop was to advise the Study planners and the Program Office about the role of genetic information in the Study. The participants introduced themselves and described their backgrounds and involvement with the Study.

Short Overview of National Children’s Study
Peter C. Scheidt, M.D., M.P.H., NICHD, NIH, DHHS

Dr. Scheidt welcomed the workshop participants and briefly reviewed the history, background, and attributes of the Study. The Study was authorized by Congress in the Children’s Health Act of 2000 (PL 106-310), which directed the NICHD to conduct a national longitudinal study of environmental influences on children’s health and development. Dr. Scheidt summarized the basic Study concepts as follows:

  • Longitudinal study of children, their families, and their environment
  • National in scope
  • Hypothesis-driven
  • Environment defined broadly (chemical, physical, behavioral, social, cultural)
  • Study common range of "environmental" exposures and less common outcomes in approximately 100,000 children
  • Exposure period begins in pregnancy
  • Environment and genetic expression (that is, gene-environment interaction)
  • State-of-the-art technology for tracking, measurement, and data management
  • Consortium of multiple agencies
  • Extensive public-private partnerships
  • National resource for future studies.

Dr. Scheidt discussed issues related to the Study population and the sampling design for the Study. The design will be a national probability sample and will have a center-based structure with multiple dense clusters. He described priority exposures and outcomes for the Study and commented that gene-environment interactions are of particular interest.

Dr. Scheidt gave examples of Study hypotheses and anticipated exposure and outcome measures. Anticipated exposure measures include:

  • Environmental samples: air, water, dust
  • Biomarkers for chemicals such as blood, breast milk, hair, and tissue
  • Interview and history
  • Serology and medical data
  • Housing and living characteristics
  • Family and social experiences
  • Neighborhood and community characteristics.

Anticipated outcome measures include:

  • Fetal growth and outcome of pregnancy
  • Birth defects and newborn exam
  • Growth, nutrition, and physical development
  • Medical condition and history: illness (for example, asthma, obesity), conditions, and injuries
  • Cognitive and emotional development
  • Mental, developmental, and behavioral conditions.

Dr. Scheidt also discussed the use of data to maximize output and presented the projected Study timeline.

Study Framework, Plan to Date, and Charge to the Working Group
Cynthia A. Moore, M.D., Ph.D.

Dr. Moore explained that genetic issues have been considered since the initial planning of the Study. She reiterated that the purpose of this workshop was to provide further consideration about the essential genetic information that needs to be collected for the Study in order to address the core hypotheses. Dr. Moore distributed a handout that summarized the 21 core hypotheses for the Study; this handout listed 8 additional hypotheses specifically related to genetic issues and described some proposed genetic studies. The additional hypotheses concern genetic factors influencing development outcomes that could be considered in the Study. The proposed genetic studies are related to specific candidate genes associated with particular outcomes. Dr. Moore noted that most of the genetic-related hypotheses focus on genomic variation of specific candidate genes. Other areas of interest include using genetic information to assess the effects of toxic exposures on gene expression and perhaps on changes in genetic material over time.

Stephanie J. London, M.D., Dr.P.H., NIEHS, NIH, DHHS, briefly reported on the Asthma Working Group’s recent discussions, particularly as related to genetics. She noted that genetic issues are fundamental to the asthma hypothesis, particularly gene-environment interactions. Dr. London said that the Asthma Working Group has addressed the following topics:

  • Ozone
  • Air pollution
  • Oxidative stress
  • Genomic DNA (including siblings and perhaps grandparents)
  • Genomic RNA
  • Haplotype reconstruction.

Sarah S. Knox, Ph.D., NICHD, NIH, DHHS, briefly reported on a recent Study workshop on gene-environment interaction and the regulation of behavior. The purpose of this workshop was to attempt to translate animal and population research from Caspi’s group into what sort of genetic investigations could be performed in the Study. This research on rats and nonhuman primates is investigating mechanisms of gene expression and polymorphisms (such as the 5HTGLPR serotonin receptor gene). Dr. Knox described behavioral outcomes (that is, alcohol consumption) in monkeys that were reared in different environments (maternal rearing versus peer rearing). She noted that, in this context, many of the tissues in which gene expression occurs are in the brain, and that this tissue cannot be studied in human subjects. Dr. Knox said that serotonin receptors in platelets do not provide a surrogate tissue for this type of research.

Types of Genetic Information to be Collected and Analyzed

To frame discussion on the types of genetic information to be collected and the types of genetic analyses to be performed, the following questions were posed to the workshop participants:

  • For what purposes can genetic information be used in studying the Study priority health outcomes—in the near term and over time?
  • What types of genetic material need to be collected?
  • What kinds of analyses for genomic variation should be considered (genotyping methods; determination of gene-disease, gene-gene, and gene-environment interaction) and how will these impact specimen requirements?
  • How can gene expression be measured, and what are the pros/cons of possible methods?
  • How can epigenetic changes be determined, and what are the pros/cons of possible methods?

Lawrence C. Brody, Ph.D., Genome Technology Branch, National Human Genome Research Institute, NIH, DHHS, asked whether transformed lymphoblast storage was being considered for the Study. He said that these cells could be collected, transformed, and then stored for future analysis. Because of the expense of this process (about $100 per sample), lymphoblasts could alternatively be frozen and then grown later for lymphocyte stimulation studies. Dr. London replied that the use of transformed lymphoblasts is being considered for the Study (that is, it is on the "wish list"). However, because of differences in time of collection and interinstitution variability, quality control issues remain for this process.

Warren Galke, M.S.P.H., Ph.D., NICHD, NIH, DHHS, briefly described the "philosophy of operation" for the Study’s specimen/sample repository. Substantial resources will be allocated to collecting and storing environmental samples and biological specimens. The intent at this time is to have a single, centralized, integrated repository. However, exactly what will be collected and stored has not yet been determined or agreed upon. Dr. Moore said that these issues would be discussed later in the workshop. There is general agreement on the importance of collecting and storing DNA samples, but the specific DNA analyses have not yet been determined. Dr. Moore asked whether this situation would affect how DNA is collected and how it can be used.

Dr. Brody noted that the cost of cryopreservation is about 25 percent of the cost of cell transformations. Cell transformations could be performed during the investigation of particular outcomes, and not in all 100,000 Study participants. In this context, participants briefly discussed:

  • Bias estimate in collecting DNA
  • Gene amplification from whole blood, not DNA extraction.

Luke Ratnasinghe, Ph.D., National Center for Toxicology Research, U.S. Food and Drug Administration, DHHS, said that because the Study will be assessing endpoint types of events, methodologies and protocols will need to capture such events. He suggested that sampling approaches should consider the collection of separate aliquots of whole blood for different purposes, such as cryopreservation, DNA analysis, and RNA analysis.

Stephen J. Chanock, M.D., Advanced Technology Center, National Cancer Institute, NIH, DHHS, said that there are several emerging issues with the candidate gene approach. Because the Study needs to make allowances for future analyses, there may need to be several simultaneous tiers of analyses, which will need good basic high-quality DNA. The Study will generally have a single opportunity to collect high-quality genetic material and will need to have a good approach for collecting DNA and other related materials.

In a discussion of DNA amplication, participants addressed:

  • In vitro procedures to amplify whole genomes without locus or allelic bias
  • Addressing issues of competitive regions
  • Epigenetics and methylation patterns
  • Destruction of methylation patterns by amplification
  • Use of mitochondrial DNA
  • Altering study design as a function of child’s age
  • Performing assays with high-quality genomic DNA
  • Future probability of large-scale sequencing
  • Aliquotting.

Participants discussed issues related to advancing technologies, including:

  • Human genome requests for applications
  • Costs of tests
  • The need to analyze all 30,000 human genes versus analyzing subsets
  • The need for sufficient amounts of genetic materials for future analyses
  • Sampling across the genome or just within coding regions (for example, haplotypes)
  • The number of genes analyzed for particular outcomes.

Regarding sources of genetic materials, participants mentioned:

  • The amount of genetic materials required for all studies/analyses
  • Cord blood samples and the amount of genetic material available from this source
  • The need for high-quality DNA
  • Mechanisms to share genetic materials
  • Gene expression studies/RNA analyses
  • Use of special collection tubes for particular analyses
  • Examples of field work specimen collection and preservation techniques
  • At-home specimen collection versus specimens collected during clinical visits
  • Endoproteomics
  • PAXgene system for RNA stabilization

Participants also discussed measuring gene expression, including:

  • Assessing temporal changes in DNA as a means to evaluate and determine toxic exposures
  • Limitations in techniques and inability to detect temporal changes
  • Relative value of different source materials (for example, serum versus plasma)
  • Minimum amounts of materials for analyses (for example, 0.5 milliliter of serum or plasma)
  • Techniques for protein expression analyses
  • Epigenetic studies
  • Tumor samples
  • Changes in samples over time
  • The need for a "zero" time point (baseline)
  • Methylation changes over the first 10 years of life
  • Specific ways of processing genetic materials to make specific observations
  • Collection of materials for serum assays
  • Questions of optimal ways to measure gene products
  • Measures of specific toxicants as indicators of specific exposures
  • Mass spectrometry of metabolites in urine, serum, plasma, and saliva
  • Urine collection issues in young children
  • Participant burden
  • Roles and responsibilities of institutional review boards (IRBs)
  • Scientific approaches for pilot studies.

Dr. Chanock urged the workshop participants to explore ideas on collecting genetic materials in a creative and scientific manner in an effort to gather the optimal set of information. He challenged the participants to be "bold and daring" in their deliberations, to not simply consider what information that can be gathered within a certain budget. Following on this theme, Dr. Galke asked participants to think creatively about possible pilot studies for the best ways to collect and store genetic samples for the Study. Geraldine McQuillan, Ph.D., National Center for Health Statistics, CDC, DHHS, reminded the participants that there are limits on what is considered to acceptable to participants and particular populations and that pilot studies and creative approaches need to be acceptable to local IRBs.

B. Alex Merrick, Ph.D., NIEHS, NIH, DHHS, briefly discussed some findings from gene expression studies. He noted that, because of circadian variations, the timing of collecting DNA- and RNA-containing samples (for example, blood draws) is important and that the Study should attempt to minimize such confounding variations. Animal studies have revealed that infections and elevations in white cell counts can affect the results of gene expression profiles in whole blood analyses.

Other topics discussed during the sessions on the types of genetic information to be collected and the types of genetic analyses to be performed for the Study include the following:

  • The total number of blood samples drawn over the course of the Study
  • Irradiation of mail and collecting home-drawn blood spots via the mail
  • Genetic materials as indicators of environmental exposures
  • Genetic databases and gene signature data sets
  • Gene expression profiles
  • Utility of whole blood samples from cord blood, peripheral blood, and blood spots
  • The need for whole blood in order collect serum to analyze RNA and proteomics
  • The need for age-specific hypotheses
  • The need for multiple phenotypic measures
  • The need for tissue-specific samples
  • The value of alternative measures of genetic materials.

Types of Specimens (Essential, Optional) From Child and Family Members

To frame the discussion on the types of specimens to be collected from children and family members, the following questions were posed to the workshop participants:

  • What are the essential specimens that should be collected from the infant for genetic studies?
  • Are there additional specimens that should be considered and what types of information will they provide (or studies will they permit)?
  • Should additional specimens be considered for the entire cohort or smaller targeted studies?
  • Which family members should be sampled and why?

The workshop participants agreed that cord blood and placental samples would provide good source materials for genetic studies. However, the participants mentioned numerous issues regarding cord blood and placental samples, including:

  • Maternal contamination of cord blood
  • The need for maternal samples and samples from other family members
  • The practicality of collecting cord blood in a delivery room setting
  • The potential value of placental samples for epigenetic studies.

Issues involving the collection and utility of neonatal buccal cells included:

  • The difficulty in collecting buccal cells immediately postpartum
  • Contamination by microbes
  • The quality and quantity of DNA collected
  • The quality and quantity of RNA collected
  • Buccal cell collection techniques.

The workshop participants briefly discussed additional specimens that should be considered, including hair and nails, and agreed that the quality and quantity of genetic materials from these sources may be limited. Additional specimens may be able to provide DNA but may not be able to provide other sources of genetic materials such as RNA and proteins and may not be able to provide epigenetic information.

Participants agreed on the value of collecting cord blood for toxicological and hematological analyses. Cord blood is also necessary to capture as close to 100 percent of germ line DNA as possible. Germ line DNA will be important in order to assess DNA changes over an individual’s life. DNA changes are important for assessing folate status and exposures to toxins and possibly to neurological trauma.

In a brief discussion of collecting specimens from the entire cohort versus smaller targeted substudies, the participants agreed on the need for a mixture of both. Also mentioned were:

  • Preterm intrauterine growth restriction
  • Preservation issues of lymphoblastoid cell lines.

In a discussion of which family members should be sampled, the participants agreed on the following:

  • Maternal samples
    • Prepregnancy
    • During pregnancy
  • Paternal samples.

Dr. Knox noted that because of possible effects of maternal psychosocial stress during pregnancy, the processing and analysis of maternal samples would be more intensive than that for paternal samples. Dr. Scheidt explained that, because of ethical issues, it would not be the Study’s place to determine or report paternity during genetic analyses. The participants briefly discussed ethical issues of reporting and counseling on suspected genetic errors. Alan R. Fleischman, M.D., NICHD, NIH, DHHS, noted that there may some obligation to report risks and benefits to families and that the time frame of sampling may play a role in this process. Andrew W. Bergen, Ph.D., Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, commented on the possible use of "fingerprinting" for each sample of cord blood and peripheral blood at different ages.

In a brief discussion of the types of genetic analyses for paternal samples, the following were mentioned:

  • Chromatin assays from sperm samples
  • RNA profiles from seminal fluid and sperm samples
  • Toxicants and indicators of toxic exposures in seminal fluid
  • Exposures affecting viability of sperm and conceptus
  • Sperm typing
  • Molecular haplotyping.

Dr. McQuillan noted that there might be compelling reasons for collecting paternal specimens, but that home sampling approaches may not be practical or feasible. This is an area that may benefit from a pilot study.

Participants agreed that genetic materials should be collected from siblings, particularly concordant siblings (that is, twins, triplets). Discordant siblings could possibly serve as controls. Cashell E. Jaquish, Ph.D., National Heart, Lung, and Blood Institute, NIH, DHHS, said that determining sibling phenotypes could provide valuable information and that blood samples from siblings should be analyzed for RNA and proteomics. The participants briefly discussed the relative scientific merit of studying materials collected from discordant siblings and grandparents.

Timing of Specimen Collection

To frame the discussion on the timing specimen collection, the following questions were posed to the workshop participants:

  • When should samples be collected?
  • Should samples be collected at multiple points of time during the study, and if so, does this differ by type of genetic material/information?
  • How will collection of genetic specimens impact other biologic studies?

There was general consensus among the workshop participants that samples of genetic materials should be collected at the following times:

  • One prenatal sample
  • One perinatal sample
  • Two or three postnatal samples.

W. Craig Hooper, Ph.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS, said that the sampling plan should be flexible in order to allow collection during unpredictable exposures such as outbreaks of West Nile disease. Dr. Scheidt agreed that there is potential benefit in taking advantage of "natural experiments." The Study should be prepared for these occurrences and should have real-time ability to sample exposures. Rubella was cited as another example of unpredictable exposures that could be studied.

Dr. Galke said that the Study’s information management system should be responsive to maximize timely data processing. One of the design principles for the Study is rapid processing of data. The participants briefly discussed laboratory management systems, adapting commercial off-the-shelf technologies, open source/closed source software, and the Study’s data model.

Ensuring a Sufficient Quantity of Material for Genetic Studies

To frame the discussion on ensuring a sufficient quantity of material for genetic studies, the following questions were posed to the workshop participants:

  • How can we ensure a sufficient amount of samples for genetic studies?
  • What methods can be used (and their pros and cons) to ensure that sufficient materials are available as studies are developed over time?

As a preface to the discussion on ensuring sufficient quantities of materials for genetic studies, Dr. Bergen presented research findings on methods development of whole genome amplification (WGA). He cautioned that researchers cannot make poor quality genomic DNA better using amplication techniques. Because it is essential to ensure quality control in WGA, the Study may want to conduct a pilot study of this methodology.

The participants briefly discussed the pros and cons of using cell lines for genetic studies, followed by a discussion about the amount of whole blood that would need to be collected and the number of analyses that would need to be performed on whole blood samples. The following analyses were mentioned:

  • Cryopreservation
  • Genomic DNA
  • WGA
  • RNA
  • Protein
  • Hematological
  • Toxicological
  • Physical chemistry.

John C. Rockett, Ph.D., Office of Research and Development, EPA, suggested that a literature search be performed to determine the minimum amount of blood necessary to perform the various analyses. The findings should be discussed, and the size of aliquots should then be determined.

Specimen Processing and Storage Issues

To frame the discussion on specimen processing and storage issues, the following questions were posed to the workshop participants:

  • What are the specimen processing and storage issues that must be considered?
  • Should any genetic studies be performed before samples are stored?
  • Are there particular processing and storage requirements for different types of genetic material or specimen types, and how do the costs, complexities vary?
  • What will be the needs for data storage and information management?

During this discussion, participants commented about the following:

  • Costs of specimen processing and various analyses
  • Pilot studies of specimen processing and storage
  • Using vanguard centers to conduct small-scale pilot studies
  • Protocol flexibility
  • Logistical issues
  • Repository challenges
  • Standardization of laboratory protocols
  • Experiences of National Health and Nutrition Examination Survey (NHANES)
  • Transcript profiling studies
  • Large-scale studies conducted by the National Cancer Institute (NCI)
  • Developing laboratory protocols by subject age
  • Lessons learned about perinatal processing from the Women and Infant Transmission Study (WITS)
  • Collecting aliquots for different purposes at different times.

In a discussion of when genetic studies should be performed, the participants noted the following:

  • CBC needs to be performed immediately.
  • Protein and physical chemistry analyses need to be performed relatively quickly.
  • RNA and plasma serum analyses should be processed quickly and consistently.
  • Frozen samples can provide relatively stable RNA profiles, for up to 100 days.

Dr. Galke explained that the location for aliquotting has not yet been determined. This task might be performed at clinical sites for preprocessing. Specimens would then be transported from the clinical sites to a central laboratory or to the repository. Dr. Galke acknowledged that the Study will collect more samples and specimens than can be processed in the short term. Samples and specimens will be collected and stored, and the ensuing analyses will be determined and performed in the future. Materials may be stored in two geographic locations to provide backup and ensure against loss in the event of disaster.

Dr. Bergen commented that annual costs for the Study could be reduced by extending the 4-year recruitment window from 4 years to 6 years, which would potentially reduce the number of subjects per year from 25,000 to approximately 17,000. This approach would reduce the annual costs of sample processing. There might be some further savings through automated processing. Carole A. Kimmel, Ph.D., Office of Research and Development, EPA, noted that extending the recruitment window would result in higher total costs and might affect the environmental exposures among the Study cohort.

Workshop participants acknowledged that issues concerning data storage and information management are extremely important to the Study, but they conceded a lack of sufficient expertise on these topics to properly discuss the issues. Participants noted that several large commercial enterprises with clinical trial experience would be better able to provide information on data storage and information management for the Study.

Participants agreed that analyzing the collected data would be challenging. The following topics were briefly discussed:

  • Public data sets and open-source materials
  • Laboratory information management systems
  • Multidimensional relational databases.

Workshop participants discussed the logistical challenges of transporting biosamples and biospecimens. Dr. Galke explained that a contracted coordinating center would handle most of the day-to-day operations of the Study. Quality control issues were briefly discussed (for example, running panels of SNPs by different processes and techniques).

Ethical, Legal, and Social Implications

To frame the discussion on the ethical, legal, and social implications for acquiring genetic information, the following questions were posed to the workshop participants:

  • How do the key issues concerning the ethical, legal, and social implications for acquiring genetic information in the Study differ in the various options?
  • Are there particular burdens to Study participants for any type of specimen collection?
  • What should be the plan for stewardship of the specimens?

Dr. Ratnasinghe explained that the Study should have clear and concise informed consent for every patient/participant. The consent document should describe the essence of the studies and analyses to be performed in simple language. This document should clearly disclose what is going to happen and should detail privacy issues and provide assurances on protection of information. Dr. Rockett asked what will be considered as genetic information and whether gene expression profiles would fall into this category. Dr. Fleischman asked whether permission for genetic testing would be optional for the Study. Given that genetic materials and biospecimens would be preserved and stored for long periods, he urged that the Study acquire consent for genetic testing as early as possible in the recruitment phase. Dr. Jaquish said that when given this option, approximately 5 percent of Study participants could be expected to not give consent. Historically, patients/participants specifically decline consent for cell lines and corporate use of genetic information.

Dr. Bergen commented that issues of informed consent are very complex. He said that NCI consent documents specify every gene that will be studied (that is, the actual SNP) and that specific consent must be granted for each studied gene. Dr. Fleischman wondered whether this approach would be practical for a sequential, longitudinal, high-burden study.

Dr. McQuillan noted that NHANES had experienced a significantly higher dropout rate among African Americans. She explained that the term "research" in consent documents is often equated with the perception of "human experiments." NHANES researchers and others have found that the term "future studies" is perceived as more preferable than "research" in consent documents.

W. Craig Hooper, Ph.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS, asked whether Study participants who initially decline to give consent can be asked again several years later. Dr. Fleischman replied that it is legal and ethical to ask for consent again in the future.

Workshop participants discussed several issues concerning obligation to inform Study participants about findings from genetic analyses. It was noted that specific genetic results do not usually appear in an individual’s medical chart, and genetic information generally cannot be introduced into clinical practice. Dr. Chanock cited an example of informing patients about genetic information on leukemia. He noted that the American College of Genetic Counselors has practices and standards regarding genetic counseling. He further noted that there are many uncertainties regarding the counseling of particular genetic results. Dr. Fleischman said that the Study intends to inform families on the results of clinically relevant tests, if applicable. He explained that the NIH has rules for informing patients regarding test results for hepatitis C and HIV. Dr. Fleischman commented that the Study would certainly report test results regarding conditions such as elevated blood lead levels and high blood pressure. Study policies for nongenetic information will be clearly stated. If the clinical implications of test results are known and important, then the patient will be informed. The patient can then provide this information to his or her physician. Whether this approach is applicable to genetic information needs to be further explored.

Dr. Bergen said that the NCI’s IRB does not permit informing individuals of specific test results. There are uncertainties regarding which test results constitute high risk, and there are ethical issues regarding the decision-making processes. However, general study results can be reported. The types of information that can and cannot be reported to NCI study participants is clearly stated upfront in the informed consent. Other issues concerning IRBs include the following:

  • Multiple IRBs (for example, state and institutional)
  • Different standards for different IRBs
  • The need of a central IRB or IRB of record.

Final Discussion and Wrap-Up

Dr. Moore summarized the workshop discussions as follows:

  • There is considerable value in collecting genetic materials such as DNA, RNA, and proteins in order to determine genomic profiles or other indicators of genetic factors that influence particular outcomes of interest in the Study.
  • One of the best options for collecting genetic materials is cord blood samples.
  • Cord blood samples should be separated into aliquots for different storage, preservation, and analytical purposes.
  • Quality control issues need to be assessed early in the collection process.
  • The collection of blood spots from newborns was recommended but may require further consideration.
  • Whole blood samples should be collected at 5—6 years of age and then again in early adolescence, at 11—12 years of age.
  • Collection, storage, and analytical approaches may need to be reconsidered for various genetic materials, for various research efforts, and as new technologies become available.
  • Other sources of genetic materials that could be collected include buccal cells and placental samples. However, there may be certain challenges and limitations to using buccal cells for gene expression analyses.
  • Sources of genetic materials such as hair and nail samples may not be acceptable for the purposes of the Study.
  • Other sources of DNA need to be considered.
  • Maternal genetic materials should be collected before conception and during pregnancy.
  • Paternal genetic materials should also be collected. Sperm collection should be considered.
  • At least one blood sample from siblings should be collected and stored. Collection of other genetic materials from siblings should be considered.

Participants

Marion J. Balsam, M.D., F.A.A.P., NICHD, NIH, DHHS
Andrew W. Bergen, Ph.D., Division of Cancer Epidemiology and Genetics, National Cancer Institute,
   NIH, DHHS
Ruth A. Brenner, M.D., M.P.H., NICHD, NIH, DHHS
Lawrence C. Brody, Ph.D., Genome Technology Branch, National Human Genome Research Institute,
   NIH, DHHS
Stephen J. Chanock, M.D., Advanced Technology Center, National Cancer Institute, NIH, DHHS
Krista Stimson Crider, Ph.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS
Terence Dwyer, M.D., M.P.H., NICHD, NIH, DHHS
Alan R. Fleischman, M.D., NICHD, NIH, DHHS
Warren Galke, M.S.P.H., Ph.D., NICHD, NIH, DHHS
Margaret Gallagher, Ph.D., National Center for Environmental Health, CDC, DHHS
W. Craig Hooper, Ph.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS
Cashell E. Jaquish, Ph.D., National Heart, Lung, and Blood Institute, NIH, DHHS
Carole A. Kimmel, Ph.D., Office of Research and Development, EPA
Sarah S. Knox, Ph.D., NICHD, NIH, DHHS
Stephanie J. London, M.D., Dr.P.H., NIEHS, NIH, DHHS
Geraldine McQuillan, Ph.D., National Center for Health Statistics, CDC, DHHS
B. Alex Merrick, Ph.D., NIEHS, NIH, DHHS
Cynthia A. Moore, M.D., Ph.D., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS
Luke Ratnasinghe, Ph.D., National Center for Toxicology Research, U.S. Food and Drug Administration,
   DHHS
John C. Rockett, Ph.D., Office of Research and Development, EPA
Peter C. Scheidt, M.D., M.P.H., NICHD, NIH, DHHS
Paula Weinstein, National Center on Birth Defects and Developmental Disabilities, CDC, DHHS