DETECTION OF RADIATION-INDUCED CHROMOSOME DAMAGE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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删除的染色体片段。然而，很大一部分细胞遗传损伤以重排的形式出现，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，易位断点的绘制是一项艰巨的任务，需要染色体带和/或整个染色体绘制，然后通过单拷贝FISH产生几个cosmids， YACs或BACs的顺序，这些cosmids包含覆盖所涉及的两条染色体上的可疑断点的基因组插入。快速准确地绘制易位断点的能力，精确到几百个碱基，将极大地促进对诸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，应该有可能在已知的BAC或cosmid序列中直接识别易位断点，作为对断点本身进行测序的前奏。反过来，这将为我们提供有关核苷酸水平上交换断点连接性质的重要信息，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起作用。对相互易位的分析比对基因缺失的分析更能全面地了解这些过程，因为易位的两个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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.