Inversion polymorphisms and non-contiguous terminal deletions: the cause and the (unpredicted) effect of our genome architecture
Inversion polymorphisms and non-contiguous terminal deletions: the cause and the (unpredicted) effect of our genome architecture
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DOI：
10.1136/jmg.2005.037671
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发表时间：
2006-05-01
影响因子：
4
通讯作者：
Zuffardi, O
中科院分区：
文献类型：
--
作者：
Ciccone, R;Mattina, T;Zuffardi, O
在BAC水平上的分子定义的8 p双着丝粒染色体和8 p缺失染色体的报告在两个不同的细胞系的患者。双着丝粒染色体起源于经典的8p23.1倒位多态性背景下的父本减数分裂过程中，其断裂点的位置不同于产生重复性inv dup del（8 p）的染色体。这种双着丝粒的断裂产生了8 p缺失的染色体，作为倒位的结果，该染色体具有两个不连续的缺失。这些发现证实了以前的数据1 p远端缺失，表明至少有一些缺失干双着丝粒染色体的断裂。他们认为，非连续缺失可能是常见的远端缺失。当两个相邻的克隆（一个缺失，另一个通过FISH分析存在）被作为缺失断裂点的边界时，这种类型的重排很容易被忽略;在这种情况下，只有高分辨率阵列CGH才能揭示它们的真实的频率。这种非连续远端缺失的定义与表型/核型相关。历史上也有因忽略第二个非连续缺失而导致错误的例子。本文展示了小规模的结构变异，如常见的多态性倒位，可能会导致复杂的重排，如末端缺失。
Molecular definition at the BAC level of an 8p dicentric chromosome and an 8p deleted chromosome is reported in a patient with two different cell lines. The dicentric, which differed from that generating the recurrent inv dup del( 8p) for the location of its break point, originated during the paternal meiosis on the background of the classical 8p23.1 inversion polymorphism. The breakage of this dicentric gave rise to the 8p deleted chromosome which, as a result of the inversion, had two non-contiguous deletions. These findings confirm previous data on 1p distal deletions, showing that at least some of the deletions stem from the breakage of dicentric chromosomes. They suggest that non-contiguous deletions may be frequent among distal deletions. This type of rearrangement can easily be overlooked when two contiguous clones, one absent and the other present by FISH analysis, are taken as boundaries of the deletion break point; in this case only high resolution array-CGH will reveal their real frequency. The definition of such non-contiguous distal deletions is relevant for phenotype/ karyotype correlations. There are historical examples of blunders caused by overlooking a second non-contiguous deletion. This paper shows how small scale structural variations, such as common polymorphic inversions, may cause complex rearrangements such as terminal deletions.