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Future of Genotyping

Executive Summary

The National Heart, Lung, and Blood Institute convened a Working Group of investigators on October 22, 2004, in Bethesda, Maryland via conference call, to evaluate current genotyping needs, opportunities, and barriers for human and animal model gene discovery. The Working Group considered the current genotyping activities of the NHLBI and addressed a number of questions concerning future efforts in genotyping needs that could be facilitated by NHLBI.


The NHLBI is committed to discovering and understanding the genetic contributions to complex diseases of the heart, lung, and blood. In 1994, the NHLBI established the NHLBI Mammalian Genotyping Service (MGS) with the Marshfield Clinical Medical Research Foundation to help investigators identify genes likely to be involved in the etiology of complex diseases. The MGS has provided whole genome linkage scans, using microsatellite markers, for the scientific community for the past ten years, and has greatly enhanced the speed with which candidate regions and genes are able to be linked to disease. To address the need to pursue these candidate regions, the Institute established the NHLBI Re-Sequencing and Genotyping Program in 2004. Since an increasing number of researchers and private companies are developing high-throughput technologies and services to perform millions of genotypes a month, the need for services such as the NHLBI MGS, whose contract is near completion, should be carefully considered. The Working Group members were asked to assess the genotyping needs of the scientific community in a number of areas: (1) needs for a service to perform genome-wide scans, including genome-wide linkage, genome-wide association, and regional genome scans; (2) sharing of genotyping data; (3) public/private partnerships to create a service for the scientific community; and (4) interaction with other public efforts in genotyping.

An overview of the MGS and its current capacity, applicant interest, and types of studies that it supports, facilitated significant discussion about the need for future genotyping services. Overall, the Working Group recommended that the NHLBI should remain involved in providing genotyping services for NHLBI-funded investigators. They discussed: (1) the current and future need for the MGS, and how to transition from the current MGS to a new model of genotyping services; (2) genotyping service(s) that would support association studies for both following up linkage results and biological candidate genes, as well as SNP-based linkage studies in humans; (3) genome-wide association studies; (4) genotyping in model organisms; (5) use of the International HapMap; and (6) the appropriate release of genotyping data to the public.


Based on the present and future genotyping needs of the scientific community, the working group members recommended ways that the NHLBI could best meet those needs. The Working Group recommended that NHLBI (in priority order):

  1. Provide Genotyping Facilities to the NHLBI Scientific Community.
    The Working Group noted that the need for high quality, cost effective genotyping for gene discovery is still significant. Over the time of the NHLBI MGS, technologies and genomic variation discovery efforts have greatly accelerated. Although the NHLBI MGS has been proactive in incorporating these changes in genotyping marker sets, the Working Group recommended that the current NHLBI MGS contract be completed as funded and that the NHLBI move to new Genotyping Facilities to facilitate gene discovery using single nucleotide polymorphisms (SNPs), as outlined below.
    • Complete the NHLBI MGS contract.
      The Working Group recommended completing the NHLBI MGS with current obligated funds, with only one more receipt date for service (instead of two receipt dates). The deadline for the last receipt date should be extended from March 30, 2005, to May 30, 2005, in order to give appropriate notice to the scientific community. The Working Group noted there will be a hiatus in genotyping between the current NHLBI MGS and a new genotyping service (see below).
    • Establish SNP Mapping Centers.
      Given the significant changes in gene mapping that have occurred over the time of the NHLBI MGS, the Working Group recommended that the NHLBI establish genotyping facilities that use SNP markers, rather than microsatelite markers. The Working Group recommended these SNP Mapping Centers initially focus on human mapping projects. These facilities could be located at multiple sites, rather than at a single site, and could be developed in cooperation with other NIH institutes. They would provide services for:
      • SNP-based genome-wide linkage studies
      • SNP-based association studies for following up on linkage results
      • SNP-based association studies for biologically relevant candidate genes
  2. Initiate A Pilot Program For Genome-Wide Association Studies.
    As the International Haplotype Map (HapMap) project nears completion, investigator interest in applying genome-wide association studies to disease gene discovery is increasing. As the Working Group noted that the technology to perform genome-wide association studies is far beyond the analytic strategies needed to gain meaningful insights from the data generated, they recommended the NHLBI initiate a pilot program for genome-wide association studies. The purpose of the pilot program would be to develop methods and test various approaches. Potential pilot projects are:
    • Test a large (multimegabases) genomic region for SNP-disease associations.
    • Test a sparse collection of SNPs (e.g., 50,000 SNPs) that span the entire genome for association with a variety of diseases.
    • Select one disease for investigation that is highly heritable. Support a project with the best sample, genotyping, and analysis plan to test the ability to understand the data handling, design, and analysis for genome-wide association. Although difficult to pick an appropriate project and the costs will be extensive, it will provide valuable information.
  3. Develop a Rodent SNP Mapping Center. The focus of SNP discovery has been in the human.
    Some additional SNP discovery efforts are being conducted in mouse, with discussions on initiating a similar program in rat. Thus, it is somewhat premature to initiate either Linkage or Association SNP Mapping Centers for all animal models. However, the Working Group noted that animal model research is key in bench to bedside efforts, systems biology approaches, and understanding function and mechanism. The Working Group recommended that NHLBI partner with other NIH Institutes to develop a Rodent SNP Mapping Center, initially in the mouse. It was also recommended that the NHLBI lead a Trans-NIH effort to determine the best way for variation discovery to proceed in other model organisms.
  4. Convene A Standing Working Group to Identify and Annotate Genes, Validate SNPs, and Identify Haplotypes.
    Curating and annotating the information derived from genomic and genetic studies is critical to understand the genetic influences on health and disease. Without standard nomenclatures and descriptions of discoveries, knowledge can be lost, duplicated, or misinterpreted. The Working Group recommended that the NHLBI convene a standing Working Group to identify and annotate genes, validate SNPs, and identify haplotypes related to heart, lung, blood, and sleep processes and diseases in order to stimulate translation of genetic and genomic findings to public health.

The working group also recommended that any new genotyping service should make the data that it produces publicly available, such that data sharing becomes and integral part of the work scope.

NHLBI Contact:

Dina N. Paltoo, Ph.D., M.P.H., NHLBI, NIH

Susan E. Old, Ph.D., NHLBI, NIH

Working Group Members

Chair: Eric Boerwinkle, Ph.D.,Human Genetics Center, University of Texas-Houston Health Science Center


  • David Ginsberg, M.D, University of Michigan
  • Joel Hirschhorn, M.D., Ph.D., Children's Hospital
  • Sharon Kardia, Ph.D., University of Michigan, Ann Arbor
  • Anne Kwitek, Ph.D., Medical College of Wisconsin
  • Susan Redline, M.D., Ph.D., Case Western Reserve University
  • Charles Rotimi, Ph.D., National Human Genome Center at Howard University
  • Gaulberto Ruano, M.D., Ph.D., Genomas, LLC.
  • Ed Silverman, M.D., Ph.D., Brigham and Women's Hospital

NIH Staff:

  • Dr. Deborah Applebaum-Bowden, DHVD, NHLBI, NIH
  • Dr. Susan Banks-Schlegel, DLD, NHLBI, NIH
  • Ms. Joanne Deshler, DEA, NHLBI, NIH
  • Dr. Gregory Evans, DBDR, NHLBI, NIH
  • Dr. Sandra Hatch, DLD, NHLBI, NIH
  • Dr. Teri Manolio, DECA, NHLBI, NIH
  • Dr. Pankaj Qasba, DBDR, NHLBI, NIH
  • Dr. Phyliss Sholinsky, DECA, NHLBI, NIH

Last updated: December 13, 2004

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