Computational Maps
Genetic maps
Since the last workshop, only one large chromosome 1 genetic map has been introduced, from the Marshfield Center for Medical Genetics (Broman et al., 1998). This map contains 669 markers from microsatellite polymorphisms previously identified by Marshfield, the University of Utah, and Généthon. The Marshfield map is also anchored at the 1q telomere by marker D1S3739. No suitable anchor for the 1p telomere has been described in the literature. Marker information, and both sex-averaged and sex-specific maps are available at www.marshmed.org/genetics/. The Marshfield web site also provides an on-line map building feature, where users can input a list of specific polymorphisms and receive a customized genetic map containing the markers of interest.
Radiation hybrid maps
Two radiation hybrid maps of the entire chromosome have been constructed recently. The Stanford Human Genome Center (SHGC) has released an on-line update (version 2.0) of their genome-wide RH map, available at www-shgc.stanford.edu/Mapping/rh/. The new version contains 946 ordered chromosome 1 markers aligned into 155 intervals with likelihood odds 3 1000:1. This is an approximately twofold increase in marker density from the previous version and yields an estimated map resolution of 1.6 Mb (Stewart et al., 1997). As before, the SHGC site includes an RH map server which provides researchers the opportunity to map their own markers scored on the G3 RH panel relative to the Stanford map. The Sanger Centre also periodically constructs an RH map of chromosome 1, which is available at the Sanger ftp site and web pages (see Resources). This map, as of June 1998, had 2665 markers that mapped to 1736 unique positions. Eighty-four Généthon genetic markers served as a framework for map construction. There are 369 markers on the map that were ordered with likelihood odds >250:1, yielding a resolution of approximately 670 Kb. The Sanger map is the most complete RH map that is currently available, and it is anticipated that 5,500 markers will eventually be integrated. Both the SHGC and Sanger maps consist largely of transcribed markers derived from gene or EST sequences.
Integrated maps
Here we define an "integrated map" as one which relates data derived from two or more distinct experimental procedures on a single scale. Three integrated maps for chromosome 1 have been generated or updated in the last year and deserve mention. The final version of the Whitehead Institute Center for Genome Research (WICGR) STS map, version 12, is now available at the WICGR web site (www-genome.wi.mit.edu/). This map integrates YAC contigs generated by STS content analysis with genetic and RH maps (Hudson et al., 1995). For chromosome 1, the physical portion of the map contains 947 STSs that were used to identify 1407 YACs. The RH map contains 1379 markers, with 220 framework markers placed at likelihood odds >250:1. Both of these datasets are aligned with the Généthon v.3 genetic map, and the RH, YAC, and genetic data are used in combination to calculate the most likely order of each marker subset. Recently, WICGR has released a set of single nucleotide polymorphic markers (SNPs), 236 of which map to chromosome 1 (Wang et al., 1998). These markers have been mapped relative to 88 Généthon microsatellites and appear to be evenly spaced throughout the chromosome. As SNPs are amenable to large-scale genomic screening technologies such as microarrays, these polymorphisms will be invaluable for future chromosome 1 research.
The Genome Database (GDB) has implemented a purely computational integrated mapping procedure, termed the GDB Comprehensive Map (gdbwww.gdb.org/gdb/compMaps.html), which assigns physical-based map locations to all markers in GDB. This procedure uses the WICGR RHmap as a standard, and the comprehensive map is built by comparing map orders of identical markers for a large number of publicly available maps. Thus, the comprehensive map is a summary of marker orders derived from various sources. In addition, cytogenetic positions and estimated physical distances are calculated for all markers. Details regarding the GDB chromosome 1 map can be found in the GDB section of this report.
At the 1997 chromosome 1 workshop, there was considerable discussion about constructing a high-resolution comprehensive map of the chromosome. This process would combine all publicly available chromosome 1 mapping data into a single map reflecting physical distance (Vance et al., 1997). It was proposed that the most effective method would relate markers to a well-ordered framework rather than to place all markers in a linear order with reduced support for order. At the current workshop, P. White presented the efforts of the White and Matise groups in constructing such a map. Their map used a series of precisely mapped genetic markers as an RH skeleton for dynamic building of a high-resolution RH framework of 289 markers, yielding a map resolution of 900 Kb with likelihood odds >1000:1. An additional 3930 unique RH markers from the Radiation Hybrid Database were then mapped relative to the framework. The researchers also built and integrated a genetic map of 820 markers in a similar process, using polymorphic markers placed on the RH map as the common integrator. Further integration of publicly available datasets allowed placement of 1998 YAC clones, 158 SNPs, and 4024 PAC clones. RH markers which represented transcripts (3038) were then screened against the Unigene collection of EST sequences to relate EST clusters with the map (Schuler et al., 1996). Finally, inferred cytogenetic positions were calculated for all of the mapped markers. This map of ~5000 markers and ~6000 large-insert clones, which is being made available at The Chromosome 1 Home Page, will be especially useful for comparison of disparate mapping data in specific regions.