Genetic Maps

The Cooperative Human Linkage Center (CHLC) has updated several of its genetic linkage maps since the last chromosome 1 workshop. Although the CHLC is no longer actively funded, part of its group and its web site has moved to the National Cancer Institute and continues to develop useful resources. The ABI PRISM linkage mapping sets are now available at several different map resolutions: low density (V1, 20 cM), medium density (V2, 10 cM), and high density (V2, 5 cM). Each are available with sex-averaged or sex-specific map distances.

Radiation Hybrid Maps

The CGAP-GAI (Cancer Genome Anatomy Project Genetic Annotation Initiative) is pursuing re-sequencing and data mining endeavors to identify single nucleotide polymorphisms (SNPs) in known genes. Re-sequencing is performed for specific cancer-related genes, and data mining approaches have been applied to NCBI's UniGene clusters (Buetow et al., 1999). To date, approximately 22,000 gene clusters have been examined, and over 700 candidate SNPs have been identified on chromosome 1. Candidate and validated SNPs have been mapped relative to the ABI PRISM V1 low density maps and GeneMap '99 using radiation hybrid map positions of their corresponding UniGene clusters.

In October of 1998, the human transcript mappng project GeneMap was upgraded to GeneMap '98 and included 30,181 gene-based markers scored in both the GB4 and G3 RH panels and mapped relative to a framework of polymorphic Généthon markers (Deloukas et al., 1998). Of these, 3114 localize to chromosome 1. Recently, this project was upgraded to GeneMap '99 with the addition of 5839 new gene-based markers to the map, 522 of which are on chromosome 1.

As part of their sequencing efforts, the Sanger Centre has updated their RH map of chromosome 1. This map was last updated in November of 1998 and currently has 5339 markers localized relative to a framework of 81 polymorphic Généthon markers.

Integrated Maps

We define an "integrated map" as one that combines data derived from two or more different experimental procedures onto a single scale. Four integrated maps have been constructed or updated since the previous workshop report. All apply computational approaches to integrate publicly available mapping data.

The Genetic Location Database (LDB) gives locations for expressed sequences and polymorphic markers by combining information from genetic linkage maps, radiation hybrid maps, physical maps, cytogenetic data and mouse homology. All markers are assigned a single unique map position and a rank value which describes the reliability of each position. Details on their well-developed and complex algorithm for map integration have been published (Collins et al., 1996). The LDB summary map has map positions for 5544 markers on chromosome 1.

The Unified Database (UDB) at the Weizmann Institute of Science integrates information on the human genome, with emphasis on mapping information (Chalifa-Caspi et al., 1998). Mapped DNA segments, classified by categories [such as genes, EST clusters and sequence-tagged sites (STSs) mapped by various methods] are presented on an integrated map estimating physical distance, along with supporting information and links to relevant databases. UDB includes data from numerous resources, including the Genome Database (GDB), The Whitehead Institute/MIT Center for Genome Research, Généthon, and GeneMap '99. UDB has information on over 6300 chromosome 1 markers.

GDB has recently updated its comprehensive maps, which integrate location data from all primary maps deposited in GDB. The updated maps now incorporate data from GeneMap '98 and GeneMap '99, including over 9000 amplimers, 5000 clones, and 700 genes on chromosome 1 (Porter et al., this report).

The CompView method for constructing comprehensive views and integrated maps has been applied to chromosome 1 (White et al., 1999). This map includes over 13,000 map elements derived from cytogenetic, meiotic linkage, radiation hybrid, physical and transcript-based mapping approaches. All of the data used for this approach are obtained form various public data repositories. The RH portion of the map forms the CompView backbone. This framework has 289 markers in unique map positions (supported with odds > 1000:1), giving a resolution of 910 kb, and an additional 5268 RH markers are mapped relative to the framework. In addition, there are 788 polymorphic markers mapped on an integrated genetic map, 239 SNPs, and 3543 transcribed markers representing 1830 Unigene EST clusters. Over 8000 large-insert clones have also been integrated with the marker set. Cytogenetic positions are either known or have been inferred for all mapped markers. CompView also determines and compositely maps sets of markers (bundles) with unique primer sequences but with shared representation of a gene or genetic marker. This unique bundling procedure simultaneously refines gene map positions, manages marker nomenclature, and identifies data errors. The CompView chromosome 1 map and data are available via graphical and text-based searches at http://genome.chop.edu (White et al., this report).