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International Large-scale Sequencing Meeting
About 50 scientists from countries publicly supporting large-scale human genome sequencing attended an international meeting in Bermuda on February 25-28, 1996. The meeting was designed to coordinate, compare, and evaluate human genome mapping and sequencing strategies; consider the potential role of new technologies in sequencing and informatics; and discuss scenarios for data release. Attendees included representatives from and scientists funded by The Wellcome Trust, U.K. Medical Research Council, Généthon, NIH National Center for Human Genome Research, DOE, German Human Genome Programme, European Commission, Human Genome Organisation (HUGO), and the Human Genome Projects of France and Japan.
Sessions were held on sequencing strategies and resources; issues related to large-scale, high-throughput sequencing; informatics; and international data dissemination. Almost every major sequencing center in the world was represented, and initial discussions focused on sequencing strategies used by each laboratory. Most groups reported pursuing highly redundant shotgun strategies followed by directed closure, although some discussed the merits of an approach in which sequencing of any region would be done initially using one-pass or low-pass sequencing. Considerable discussion led to the consensus that the final product representing the first human genome sequence should be done at high accuracy.
Sequencing
Only a few human chromosomes (16, 19, 21, 22, and X) clearly have enough sequence-ready clones to initiate immediate sequencing, and only partial maps are available for some of these. Thus many major groups felt that building sequence-ready maps and clones must be integrated with plans for large-scale sequencing. In many cases this would involve converting low-resolution YAC maps to sequenceable clones such as BACs, PACs, or cosmids. For chromosomes without clonal coverage, BAC maps could be generated. Both the mapped BAC and cosmid substrates were considered suitable starting points for large-scale sequencing. Attendees developed a folder of each laboratory's resources available for contribution to the public domain.
Informatics
The informatics session revealed that a variety of software tools provide alternatives to commercially available packages for sequence-data assembly and analysis. These programs, which offer substantial advantages over previous packages, generally are available free to universities and nonprofit institutes via ftp servers. Many investigators are using the new programs Phred and Phrap by Phil Green (University of Washington, Seattle), which have greatly improved accuracy and editing capabilities.
Dissemination Guidelines
The following principles were endorsed unanimously by the attendees.
* All human genomic sequence data generated by centers funded for large-scale human sequencing should be freely available and in the public domain to encourage research and development and to maximize the benefit to society.
* Sequence assemblies should be released as soon as possible; in some centers, assemblies larger than 1 kb would be released automatically on a daily basis.
* Finished annotated sequence should be submitted immediately to public databases.
* These principles should apply to all human genomic sequences generated by public large-scale sequencing centers to avoid having such centers establish a privileged position in exploitation and control of human sequence information.
* To promote coordination, large-scale sequencing centers should inform HUGO of their intention to sequence particular regions of the human genome. HUGO would present this information on its WWW page and link to individual centers for more detailed information regarding specific regions. Centers could thus declare their interactions in a general framework while allowing detailed interrogation at the local level.
Attendees agreed that meetings of this type should be held annually to discuss new technologies and data dissemination in coordinating human genome sequencing worldwide.
A final poll was conducted at the end of the meeting to determine the sequencing targets and goals of each laboratory. If funding requested from granting agencies is forthcoming, the projected total of human sequence over the next 3 to 5 years would be about 1 billion bases or one-third the human genome. This goal depends on substantial technology improvements and cost reductions. Some laboratory representatives also indicated that they would sequence targeted regions simultaneously in human and mouse genomes.
By: Aaron Hall
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