DETECTION OF RADIATION-INDUCED CHROMOSOME DAMAGE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 为了研究基因组的结构变化，迄今为止，微芯片阵列仅限于检测扩增或缺失的染色体片段。 然而，很大一部分细胞遗传学损伤的形式是重排，如不同染色体之间的易位，这是微阵列分析无法检测到的。 就目前而言，易位断裂点的定位是一项艰巨的任务，需要染色体显带和/或全染色体涂染，然后进行单拷贝FISH以产生包含基因组插入物的几个cosmetry、YAC或BAC的排序，所述基因组插入物覆盖所涉及的两条染色体上的疑似断裂点。如果能够快速而准确地将易位断裂点定位到几百个碱基之内，将大大促进对这种重排（如电离辐射产生的重排）的研究。 随着基因组阵列覆盖密度的提高，应该有可能直接鉴定已知BAC或粘粒序列内的易位断裂点，作为对断裂点本身进行测序的前奏。 反过来，这将为我们提供关于核苷酸水平上交换断点连接的性质的重要信息，例如，DNA同源性是否（或在多大程度上）在畸变形成的重组过程中发挥作用。相互易位的分析比基因缺失的分析更全面地了解这些过程，因为易位的两种重组产物都是可恢复的。

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.