Introduction 



cloned sequences from single human chromosomes are produced for the research 

 community. Thus, the Human Genome Initiative was a natural outgrowth of ongoing 

 DOE-supported research. 



OHER responded to the Santa Fe meeting and HERAC reports by implementing three 

 major objectives that are being pursued concurrently: 



1. The generation of refined physical maps of the chromosomes, including the ordering 

 of representative libraries of DNA clones. 



2. The development of requisite supportive strategies, chromosomal resources, and 

 instrumentation, which includes development and testing of advanced sequencing 

 technologies. 



3. The expansion of communication networks and computational and database 

 capacities and the development of advanced algorithms for managing and 

 interpreting the clone ordering and sequence data. 



A small number of genes or other selected regions of interest will be sequenced during 

 the generation of physical maps; however, the transition from mapping to an intensive 

 genome-sequencing effort awaits development of more accurate, rapid, and economical 

 technologies that are needed to commence large-scale sequencing. Once suitable new 

 technologies are implemented, contiguous segments of DNA will be decoded into a 

 reference .sequence of the human genome. These segments will be derived from ordered 

 clones and DNA fragments that are identified or mapped to particular locations on 

 chromosomes by sequence-tagged sites (STSs) or other methodologies. Emerging 

 methodologies will be tested and validated in pilot sequencing projects prior to 

 incorporating any single protocol as the primary method. 



As implementation of the OHER program began with a small number of pilot projects, 

 other government agencies, scientific societies, and commercial organizations initiated 

 their own studies of associated policy and strategy issues and presented their 

 recommendations. The most prominent reports are those of the National Research 

 Council (NRC) and the Congressional Office of Technology Assessment (OTA). While 

 broadly in accordance with the earlier HERAC recommendations, the NRC and OTA 

 reports further recommended that several nonhuman species also be included in the 

 national effort and that the physical mapping of chromosomes be complemented by 

 genetic mapping. 



The OHER human genome program remains focused on physical map construction and 

 development of advanced sequencing methodologies and technologies. Because many 

 of the resources and technologies being developed have broad applicability, they 

 contribute substantially to OHER programmatic objectives in the fields of radiation 

 biology, chemical toxicology, molecular epidemiology, and the ecological and 

 environmental biosciences and aid the developing genome programs of other agencies 

 as well. 



