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:
- Table A: YAC vs. RH hybridizations. IRS-PCR products of RHs
are used to rapidly probe YACs on densely gridded filters via highly
parallel hybridization experiments.
- Table B: RH vs. STS PCR amplifications. The STSs are compared
against the RHs using PCR; these experiments can be highly
parallelized. IPM then combines tables A and B to produce a computed
table C of YAC vs. STS comparisons. Each YAC row of C is a profile
against STS sample points; the peak of each profile serves to localize
the YAC on the chromosome.
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.