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Bioinformatics. A Practical Guide to the Analysis of Genes and Proteins - Baxevanis A.D.

Baxevanis A.D. Bioinformatics. A Practical Guide to the Analysis of Genes and Proteins - New York, 2001. - 493 p.
ISBN 0-471-22392-1
Download (direct link): bioinformaticsapractic2001.pdf
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Figure 6.4. GeneMap '99. Example segment of The Human Gene Map, showing the first map interval on human chromosome 22q. Although the figure indicates that the map begins at a telomere, on this acrocentric chromosome, it actually begins near the centromere. The lower section of the figure contains 6 columns describing the elements mapped to this interval: column 1 gives cM linkage map positions for the polymorphic markers (none shown here); column 2 shows the computed cR position on either the GB4 or G3 portion of the GeneMap; column 3 contains either an F (for framework markers), or P followed by a number. This value represents the difference in statistical likelihood (lod score) for the given map position versus the next most likely position. A lod score of 3 is equivalent to odds of 1000:1 in favor of the reported marker position, 2 is equivalent to odds of 100:1, and a lod score of 1 represents odds of 10:1. Columns 4, 5, and 6 provide marker and gene names (if known).
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GENOMIC MAPPING AND MAPPING DATABASES
searchable relational database that stores RH score data and RH maps. Data submission and retrieval are completely open to the public. Data are available in multiple formats or as flatfiles. Release 18.0 (September 2000) contained over 126,000 RH entries for 100,000 different STSs scored on 15 RH panels in 5 different species, as well as 91 RH maps.
STS Content Maps and Resources
Many physical mapping techniques have been used to order genomic segments for regional mammalian genome mapping projects. However, only RH and STS content/ large-insert clone mapping methods have yielded the high throughput and automation necessary for whole-genome analysis to date, although advances in sequencing technology and capacity have recently made sequence-based mapping feasible. Two landmark achievements by the CEPH/Genethon and WICGR groups have mapped the entire human genome in YACs. The most comprehensive human physical mapping project is the collection of overlapping BAC and PAC clones being identified for the human DNA sequencing project, along with the now complete draft sequence of the human genome. This information is being generated by many different labs, and informatics tools to utilize the data are rapidly evolving.
The WICGR physical map is STS content based and contains more than 10,000 markers for which YAC clones have been identified, thus providing an average resolution of approximately 200 kb (Hudson et al., 1995). This map has been integrated with the Genethon GL and the WICGR RH maps. Together, the integration provides STS coverage of 150 kb, and approximately half the markers are expressed sequences also placed on GM99. The map was generated primarily by screening the CEPH MegaYAC library with primers specific for each marker and then by assembling the results by STS content analysis into sets of YAC contigs. Contigs are separately divided into ‘‘single-linked’’ and ‘‘double-linked,’’ depending on the minimum number of YACs (one or two) required to simultaneously link markers within a contig. Predictably, the double-linked contigs are shorter and much more reliable than the single-linked ones, largely because of the high chimeric rate of the MegaYAC library. Thus, some skill is required for proper interpretation of the YAC-based data.
The WICGR Human Physical Mapping Project Home Page provides links to downloadable (but large) GIFs of the maps, a number of ways to search the maps, and access to the raw data. Maps can be searched by entering or selecting a marker name, keyword, YAC, or YAC contig. Text-based displays of markers list marker-specific information, YACs containing the marker, and details of the associated con-tig. Contig displays summarize the markers contained within them, along with their coordinates on the GL and RH maps, which is a very useful feature for assessing contig integrity. Details of which YACs contain which markers and the nature and source of each STS/YAC hit are also shown. Clickable STS content maps are also provided from the homepage, and users have the option of viewing the content map alone or integrated with the GL and RH maps. Although there are numerous conflicts between the GL, RH, and STS content maps that often require clarification with other techniques, this resource is very informative once its complexities and limitations are understood, especially where BAC/PAC/sequence coverage is not complete and in linking together BAC/PAC contigs.
MAPPING PROJECTS AND ASSOCIATED RESOURCES
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The CEPH/Genethon YAC project is a similar resource to the WICGR project, also centered around screening of the CEPH MegaYAC library with a large set of STSs (Chumakov et al., 1995). Much of the CEPH YAC screening results have been incorporated into the WICGR data (those YAC/STS hits marked as C). However, the CEPH data includes YAC fingerprinting, hybridization of YACs to inter-Alu PCR products, and FISH localizations as complementary methods to confirm contig holdings. As with WICGR, these data suffer from the high YAC chimerism rate; long-range contig builds should be interpreted with caution, and the data are best used only as a supplement to other genomic data. The CEPH YAC Web site includes a rudimentary text search engine for STSs and YACs that is integrated with the Genethon GL map, and the entire data set can be downloaded and viewed using the associated QUICKMAP application (Sun OS only; Chumakov et al., 1995).
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