  In the project's early years, Norton Zinder, who chaired the NIH's Program Advisory Committee for the Human Genome, characterized it in this way: “This Project is creating an infrastructure for doing science; it's not the doing of the science per se. it will provide the biological community with the basic materials for doing research in human biology” (in Cooper 1994, p. 74). The published human genome reference sequences are part of that infrastructure, serving as tools for investigating human genetic variation. So far gene identification has been successful for the single genes of large effect implicated in rare Mendelian disorders. Difficulties arise for identifying the multiple genes of variable effect that interact with nongenetic factors in more common, complex conditions and for understanding the physiological processes associated with the development of these phenotypes. One approach to overcoming these difficulties focuses on relatively genetically homogeneous populations with members for whom extensive clinical data are available, as in the case of the Icelandic genome project, and basically extends the methods used for linkage mapping for diseases within families. Another approach is to conduct large-scale case-control association studies between phenotypes of interest and genetic markers. For both these approaches, single nucleotide polymorphisms (SNPs) are preferred as markers over the microsatellites used for genetic and physical mapping by the HGP. Worried about the private sector's efforts to patent SNPs, which would make them costly to use for research, the NHGRI-DOE's five-year plan for 1998–2003 included the goal of mapping 100,000 SNPs by 2003 (Collins et al. 1998). The development of a public database of SNPs received a $138 million push from the International HapMap Project, a three-year public-private partnership completed in 2005 that mapped variation in four population groups. The NHGRI's involvement in the HapMap Project was part of the continuing leadership role in genome research it envisioned for itself upon completion of the HGP (Collins et al. 2003). Other projects include ENCODE, which began as a pilot project to study gene function by analyzing one percent of the genome and is now looking at the remaining 99 percent, and more recently, clinENCODE, in which disease risk is being calculated for 400 people based on the corresponding one percent of the genome as a step toward personalized medicine. However, the infrastructure of mapping and sequencing technologies developed as part of the HGP—especially the ability to sequence entire genomes of organisms—has changed the way biology, not just human biology, is done. It is now recognized that genome structure by itself tells us only so much. In functional genomics, the interest is in how genomes—not just individual genes anymore—function. By studying the coordinated expression of the genome's various segments in different tissues at different times, researchers are coming to better understand organismal development. In comparative genomics, the study of genomic structure and function in different species is bringing about similar gains in understanding evolution. And genomics is now complemented by the field of proteomics which studies the structure and function of all of an organism's proteins, called the proteome.