Inner Product Mapping: Validation on Chromosome 11 Data

Mark W. Perhn and Charles W. Richard III*

School of Computer Science, Carnegie Mellon University, Pittsburgh
*Departments of Psychiatry and Human Genetics, University of Pittsburgh, Pittsburgh

Integrated physical/genetic maps of humans and other model organisms are crucial for the positional cloning of genes. Toward this end, considerable effort has been expended world-wide on mapping yeast artificial chromosomes (YACs) relative to sequence tagged sites (STSs). The current best method is STS-content mapping, which directly compares YACs (or YAC pools) against STSs for overlap. Since this method requires that each YAC overlap two STSs, considerable experimentation is needed, and best results are obtained using large, low-resolution MegaYACs.

Inner product mapping (IPM) [1] was devised in order to reduce by several orders of magnitude the experimental time, effort, and cost of map construction. Rather than directly comparing YACs vs. STSs, IPM uses a third reagent, radiation hybrids (1111), as a probe. Two tables are constructed:

We report here the first experimental validation of IPM using preliminary data from chromosome 11. In this partial, in-progress data set, table A compares 1728 350kb YACs against 65 RHs. Table B compares these same 65 RHs- against 182 STSs, providing roughly 1MB STS resolution. (The complete data set will repeat all the YAC hybridizations, and have 84 RHs with 506 STSs.) Of the 1100 YACs that produced Alu-PCR products, more than half were precisely positioned by IPM. To assess accuracy, a set of YACs that were localized by STS-content was used; these map to the STS marker CRYA2. For six YACs (by plate number: 2G7, 4117, 15E3, 15E4, 17F12, and 17114) in this co-localizing set, IPM profiles were computed from the partial data. The major peaks of these YACs' profiles respectively localize to the STS position numbers 138, 137, 137, 137, 137, and 137. The STS at position number 137 is, in fact, the marker CRYA2. This correct (5/6) co-localization provides the first definitive physical mapping confirmation (by STS content) that IPM accurately localizes YACs.

[1] Perlin, M.W., and Chakravarti, A. (1993). Efficient Construction of High-Resolution Physical Maps from Yeast Artificial Chromosomes using Radiation Hybrids: Inner Product Mapping. Genomics, 18: 283-289.

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Document last modified on March 28, 2000.