DETECTION OF RADIATION-INDUCED CHROMOSOME DAMAGE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 为了研究基因组的结构变化，到目前为止，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采取重排的形式，例如不同染色体之间的易位，这是微阵列分析无法检测到的。目前，易位断点的图谱是一项艰巨的工作，需要染色体显带和/或整个染色体涂色，然后通过单拷贝FISH产生几个宇宙体、YAC或BAC的排序，这些宇宙体、YAC或BAC包含覆盖所涉及的两条染色体上的可疑断裂点的基因组插入。能够快速而准确地绘制易位断点图，精确到几百个碱基以内，将极大地促进对这种重排的研究，例如由电离辐射产生的重排。随着基因组阵列覆盖密度的提高，直接识别已知BAC或粘粒序列中的易位断点应该是可能的，作为对断点本身进行测序的前奏。这反过来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)在导致异常形成的重组过程中发挥作用。对相互易位的分析比对基因缺失的分析更全面地描述了这些过程，因为对于易位，两种重组产物都是可以恢复的。

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.