DETECTION OF RADIATION-INDUCED CHROMOSOME DAMAGE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. For the purposes of studying structural changes to the genome, microchip arrays have to date been limited to the detection of either amplified or deleted chromosomal segments. However, a large fraction of cytogenetic damage takes the form of rearrangements, such as translocations between different chromosomes, which microarray analysis cannot detect. As it stands now, the mapping of translocation breakpoints is an arduous undertaking, requiring chromosome banding and/or whole chromosome painting, followed by single-copy FISH to yield an ordering of several cosmids, YACs or BACs containing genomic inserts that cover the suspected breakpoint on both chromosomes involved. The ability to map quickly and accurately translocations breakpoints, to within a few hundred kilobases, would greatly facilitate the study of such rearrangements such as those produced by ionizing radiations. As the density of coverage of genomic arrays improves, it should be possible to identify directly translocation breakpoints within a known BAC or cosmid sequence, as a prelude to sequencing the breakpoint itself. This, in turn, will give us vital information concerning the nature of the exchange breakpoint junction at the nucleotide level, for example, whether (or to what degree) DNA homology plays a role in the recombinational process underlying aberration formation. Analysis of reciprocal translocations yields a fuller picture of these processes than, for example, analysis of gene deletions, since with translocations both recombinational products are recoverable.