Chromosome 1 Websites

Currently available on the internet are three websites dedicated specifically to chromosome 1 research and information. These are the Chromosome 1 Home Page at Rutgers University, the Human Genome Organization (HUGO)-sponsored Chromosome 1 page, and the Sanger Centre's Human Chromosome 1 Project (see also Table 1 for web addresses). All 3 sites have been in existence for several years and have been described in more detail in previous workshop reports. The Chromosome 1 Home Page was recently moved intact from its former site at Rockefeller University, and the European mirror site has likewise moved to its new host at the UK Human Genome Mapping Project Resource Centre. This site includes user-submitted chromosome 1 data, an on-line discussion forum and email list, a chromosome 1 researcher directory, Chromosome 1 Workshop reports and information, and both public and research-oriented resource sections. The HUGO site includes an extensive list of internet links to chromosome-specific data sets and related resources. The Sanger website serves as a repository for data generated by Sanger's chromosome 1 mapping and sequencing teams. The site includes links to primary sequence data, a mapping section detailing radiation hybrid and large-insert clone mapping efforts, sequence progress statistics, chromosome 1- and Sanger-specific BLAST utilities, and direct web-based queries of the project's extensive mapping database, 1ace.

 Genomic Resources

A number of Internet sites containing relevant and informative chromosome 1 data were developed since the last workshop (Table 1). Update presentations for two of these were presented at this year's workshop. Simon Gregory presented an overview of the chromosome 1 mapping and sequencing datasets and analysis tools available at the Sanger Website (see also Sanger section). Erik Sulman demonstrated the latest features of the chromosome 1 genomic cataloguing project CompView, which integrates mapping, sequence, and functional data from chromosome 1 into a single map and searchable/viewable database (White et al., 1999b). CompView will be incorporated into a genome-wide cataloguing effort entitled eGenome, which is expected to be available on-line in early 2001, and which will include a wider range of sequence-based data and analysis tools.

The National Center for Biotechnology Information (NCBI) continues to compile the largest publicly available set of genomic information, much of which can be viewed in a chromosome-specific manner. The NCBI Map Viewer utility is a powerful graphical viewing tool that relates clone contigs to draft and annotated genomic sequence as well as to previously published radiation hybrid and genetic linkage maps. Map Viewer provides a convenient means to zoom in and out of a region of interest, to maneuver between sequence, clone, and map-based information, and to access related information for specific genomic elements, such as GenBank and UniGene records. The Map Viewer page for chromosome 1 also provides links to all curated chromosome 1 loci (housed in LocusLink), chromosome 1 UniGene clusters, known mouse orthologs, cancer-derived chromosome 1 aberrations, and an updated sequencing status. As of November 2000, 32.6 Mb (12.4%) of chromosome 1 had been completely sequenced.

The joint Sanger/European Bioinformatics Institute (EBI) Ensembl project is a web-based system for browsing genomic information somewhat analogous to the NCBI's Map Viewer. The chromosome 1 Ensembl entry page aligns the cytogenetic and GeneMap '99 RH maps with draft/finished genomic sequence contigs. This page leads to more detailed displays of clone contigs and sequence information, including graphical displays of sequence tracts showing annotated genes, predicted open reading frames, gene structures, and additional genomic features. Also integrated into Ensembl are identified SNPs and known disease loci.

In addition, the University of California at Santa Cruz's (UCSC) Draft Human Genome Browser can be used to view a local assemblage of the human draft sequence. This graphical interface presents annotated features of genomic sequence tracts that have been ordered along each chromosome. Features included in the viewer are the chromosome band, genetic linkage markers, clone coverage, gaps in the sequence assemblages, quality of sequence coverage for a region, known and predicted genes, EST homologies, CpG islands, CG isochores, repetitive elements, and homologies to pufferfish genome sequence. Like Map Viewer and Ensembl, the graphical displays can be manipulated to the user's choosing. However, use of this system requires some prior knowledge of the region to be viewed in terms of estimated base pairs from the 1p telomere.

Equating cytogenetic positions with other genomic information has previously been difficult, but in addition to the integration resources such as CompView, Map Viewer, and Ensembl, a number of well-defined datasets linking map and cytogenetic band-derived localizations have emerged in the last year. Chromosome 1-specific sets of large-insert clones, known to contain well-positioned genetic linkage or radiation hybrid markers, have been developed by several groups, including the Cancer Chromosome Aberration Project (CCAP; 98 localized chromosome 1 clones), the University of Washington Department of Molecular Biotechnology (UWDMB; 217 clones), the Children's Hospital of Oakland Research Institute (CHORI; 358 clones), the Cedars-Sinai Medical Center (CSMC; 90 clones), and the Max Planck Institute of Molecular Genetics (MPIMG; 208 clones) (Korenberg et al., 1999; Wheeler et al., 2000). All clones in each set have been positioned to a specific chromosome band by fluorescence in situ hybridization. In all cases, clones are derived from public domain libraries, with individual clones available for purchase from several commercial vendors. Large-insert clones and corresponding PCR-based markers have recently been identified for both the 1p and 1q telomeres (Knight et al., 2000).

Three resources have generated lists of single nucleotide polymorphisms (SNPs) that have been localized to chromosome 1. The NCBI maintains a repository of SNPs, dbSNP, which includes a set of non-redundant chromosome 1 SNPs that have been assigned to a sequence contig and ordered along the chromosome (Wheeler et al., 2000). As of November 2000, this set includes 1791 SNPs with an average intermarker distance of 234 kb; the set can be downloaded directly or browsed using Map Viewer. The SNP Consortium (TSC) has created a web interface for browsing SNPs by chromosome; currently, TSC lists 20,719 SNPs that map in some regard to chromosome 1, although the chromosomal assignments for the TSC set are not generally as reliable as for dbSNP. The TSC website includes detailed information about each SNP as well as information regarding the sequence source and sequence contig, if available. Finally, the National Cancer Institute's Genetic Annotation Initiative (GAI) has identified a large number of SNPs that have been used to genotype the CEPH pedigrees. The GAI project has subsequently used this genotyping information to construct genetic linkage maps of the typed SNPs. The GAI chromosome 1 map includes 858 SNPs, and the SNP locations have been integrated with existing RH and genetic linkage maps (Clifford et al., 2000).