A new plan, for 1998-2003, is presented, in which human DNA sequencing will be the major emphasis. Some goals were in the same areas of the first five years plan but different in the quantitative feature. Some new goals were added preparing for the further study after human DNA sequence is complete those goals are human DNA sequence variation and the studying of functional genomics. Goals about Bioinformatics and Computational Biology were also added to improve data collection and analytical tools.

1 The Human DNA Sequence

Providing a complete, high-quality sequence of human genomic DNA to the research community as a publicly available resource continues to be the Human Genome Projects highest priority goal. Recent technological developments and experience with large-scale sequencing provide increasing confidence that it will be possible to complete an accurate, high-quality sequence of the human genome by the end of 2003, two years sooner than previously predicted. Finish the complete human genome sequence by the end of 2003. Finish one-third of the human DNA sequence by the end of 2001. Achieve coverage of at least 90% of the genome in a working draft based on mapped clones by the end of 2001. Make the sequence totally and freely accessible

2 Sequencing technology

In the future, de novo sequencing of additional genomes, comparative sequencing of closely relate genomes, and sequencing to assess variation within genomes will become increasingly indispensable tools for biological and medical research. Much more efficient sequencing technology will be needed than is currently available.

Continue to increase the throughput and reduce the cost of current sequencing technology.

Support research on novel technologies that can lead to significant improvements in sequencing technology.

Develop effective methods for the advanced development and introduction of new sequencing technologies into the sequencing process.

3 Human genome sequence variation

The most common polymorphisms in the human genome are single base-pair differences, also called single-nucleotide polymorphisms (SNPs). When two haploid genomes are compared, SNPs occur every kilobase, on average. Basic information about the types, frequencies, and distribution of polymorphisms in the human genome and in human populations is critical for progress in human genetics. Better high-throughput methods for using such information in the study of human disease is also needed.

Dense maps of SNPs will make possible genome-wide association studies, which are a powerful method for identifying genes that make a small contribution to disease risk.

Develop technologies for rapid, large-scale identification or scoring, or both, of SNPs and other DNA sequence variants.

Identify common variants in the coding regions of the majority of identified genes during this 5-year period.

Create an SNP map of at least 100,000 markers. Develop the intellectual foundations for studies of sequence variation. Create public resources of DNA samples and cell lines.

5 Technology for functional genomics

The availability of entire genome sequences is enabling a new approach to biology often called functional genomics the interpretation of the function of DNA sequence on a genomic scale.The next step after knowing the structure of a gene or other element is to elucidate function, which results from the interaction of genomes with their environment. The Human Genome Project should contribute to this area by emphasizing the development of technology that can be used on a large scale, is efficient, and is capable of generating complete data for the genome as a whole. Large-scale characterization of the gene transcripts and their protein products underpins functional analysis. Therefore, identifying and sequencing a set of full-length cDNAs that represent all human genes must be a high priority.

Develop cDNA resources.

Support research on methods for studying functions of non-protein-coding sequences.

Develop technology for comprehensive analysis of gene expression.

Improve methods for genome-wide mutagenesis. Creating mutations that cause loss or alteration of function.

Develop technology for global protein analysis.

6 Comparative genomics

In order to understand the human genome fully, genomic analysis on a variety of model organisms closely and distantly related to each other must be supported. Genome sequencing of E. coli and S. cerevisiae, two of the five model organisms targeted in the first 5-year plan, has been completed. Completion of the DNA sequence of the remaining model organisms, C. elegans, D. melanogaster, and mouse, continues to be a high priority and should proceed as rapidly as available resources allow. Additional model organisms will need to be analyzed to allow the full benefits of comparative genomics to be realized. This ongoing need is a major rationale for building sustainable sequencing capacity.

Complete the sequence of the C. elegans genome in 1998.

Complete the sequence of the Drosophila genome by 2002.

Complete the mouse genome by 2005.

Identify other model organisms that can make major contributions to the understanding of the human genome and support appropriate genomic studies.

7 Ethical, Legal, and Social Implications (ELSI)

The advances in the understanding of human genetics and genomics will have important implications for individuals and society. Examination of the ethical, legal, and social implications of genome research is, therefore, an integral and essential component of the Human Genome Project. The major ELSI goals for the next 5 years are:

Examine the issues surrounding the completion of the human DNA sequence and the study of human genetic variation.

Examine issues raised by the integration of genetic technologies and information into health care and public health activities.

Examine issues raised by the integration of knowledge about genomics and gene-environment interactions into nonclinical settings.

Explore ways in which new genetic knowledge may interact with a variety of philosophical, theological, and ethical perspectives.

Explore how socioeconomic factors and concepts of race and ethnicity influence the use, understanding, and interpretation of genetic information, the utilization of genetic services, and the development of policy.

8 Bioinformatics and computational biology

Bioinformatics support is essential to the implementation of genome projects and for public access to their output. Bioinformatics needs for the genome project fall into two broad areas: (i) databases and (ii) development of analytical tools. The research community needs computational methods that will allow scientists to extract, view, annotate, and analyze genomic information efficiently. Thus, the genome project must continue to invest substantially in these are.

Improve content and utility of databases.

Develop better tools for data generation, capture, and annotation.

Develop and improve tools for representing and analyzing sequence similarity and variation

Create mechanisms to support effective approaches for producing robust, exportable software that can be widely shared

9 Training

The HGP has created the need for new kinds of scientific specialists who can be creative at the interface of biology and other disciplines, such as computer science, engineering, mathematics, physics, chemistry, and the social sciences. Programs must be developed that will encourage training of both biological and nonbiological scientists for careers in genomics. Especially critical is the shortage of individuals trained in bioinformatics.

Nurture the training of scientists skilled in genomics research.

Encourage the establishment of academic career paths for genomic scientists.

Increase the number of scholars who are knowledgeable in both genomic and genetic sciences and in ethics, law, or the social sciences
 

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