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首页> 外文期刊>Seminars in cancer biology >Genomic rearrangements in inherited disease and cancer.
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Genomic rearrangements in inherited disease and cancer.

机译：遗传性疾病和癌症中的基因组重排。

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Genomic rearrangements in inherited disease and cancer involve gross alterations of chromosomes or large chromosomal regions and can take the form of deletions, duplications, insertions, inversions or translocations. The characterization of a considerable number of rearrangement breakpoints has now been accomplished at the nucleotide sequence level, thereby providing an invaluable resource for the detailed study of the mutational mechanisms which underlie genomic recombination events. A better understanding of these mutational mechanisms is vital for improving the design of mutation detection strategies. At least five categories of mutational mechanism are known to give rise to genomic rearrangements: (i) homologous recombination including non-allelic homologous recombination (NAHR), gene conversion, single strand annealing (SSA) and break-induced replication (BIR), (ii) non-homologous end joining (NHEJ), (iii) microhomology-mediated replication-dependent recombination (MMRDR), (iv) long interspersed element-1 (LINE-1 or L1)-mediated retrotransposition and (v) telomere healing. Focussing on the first three of these general mechanisms, we compare and contrast their hallmark characteristics, and discuss the role of various local DNA sequence features (e.g. recombination-promoting motifs, repetitive sequences and sequences capable of non-B DNA formation) in mediating the recombination events that underlie gross genomic rearrangements. Finally, we explore how studies both at the level of the gene (using the neurofibromatosis type-1 gene as an example) and the whole genome (using data derived from cancer genome sequencing studies) are shaping our understanding of the impact of genomic rearrangements as a cause of human genetic disease.
机译：遗传性疾病和癌症中的基因组重排涉及染色体或较大染色体区域的总体改变，并且可以采取缺失，重复，插入，倒位或易位的形式。现在已经在核苷酸序列水平完成了许多重排断裂点的表征，从而为详细研究基因组重组事件基础的突变机制提供了宝贵的资源。更好地了解这些突变机制对于改进突变检测策略的设计至关重要。已知至少五类突变机制会导致基因组重排：（i）同源重组，包括非等位基因同源重组（NAHR），基因转化，单链退火（SSA）和断裂诱导复制（BIR），（ ii）非同源末端连接（NHEJ），（iii）微同源介导的复制依赖性重组（MMRDR），（iv）长时间散布的element-1（LINE-1或L1）介导的逆转座和（v）端粒修复。着眼于这些一般机制的前三个，我们比较并对比了它们的标志性特征，并讨论了各种局部DNA序列特征（例如，促进重组的基序，重复序列和能够形成非B DNA的序列）的作用。重组事件构成了总体基因组重排的基础。最后，我们探索在基因水平（以1型神经纤维瘤病基因为例）和整个基因组（从癌症基因组测序研究获得的数据）水平的研究如何形成对基因组重排影响的理解人类遗传疾病的原因。

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