The common fragile site FRA16D and its associated gene WWOX are highly conserved in the mouse at Fra8EI
The common fragile site FRA16D and its associated gene WWOX are highly conserved in the mouse at Fra8EI
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DOI：
10.1002/gcc.10047
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发表时间：
2002-06-01
影响因子：
3.7
通讯作者：
Smith, DI
中科院分区：
文献类型：
--
作者：
Krummel, KA;Denison, SR;Smith, DI
最近，几个常见的脆性位点（CFS）已被克隆和表征，包括两个最常见的人群中观察到的，FRA 3B和FRA 16 D。除了它们的高断裂频率之外，FRA 3B和FRA 16 D与跨越大断裂区域的基因共定位。在FRA 3B处，脆性组氨酸三联体（FHIT）基因跨越超过1 Mb，并且在FRA 16 D处，WWOX基因跨越超过750 kb。还已经表明，在小家鼠中，CFS Fra 14 A2和小鼠Fhit基因在基因组的正向区域中是保守的。在这项研究中，我们将WWOX（Wox 1）的直系同源物定位在小鼠基因组的染色体带8 E1。为了确定是否像FraI 4A 2、Fhit Fra 8 EI和Wox 1一样在小鼠体内共定位，我们制备了细菌和酵母人工染色体探针，并将它们与蚜虫菌素处理的小鼠中期染色体杂交。我们的数据表明，WoxI与Fra 8 E1共定位。此外，来自该区域的序列，包括内含子，在至少100-kb区域上高度保守。这种进化上的保守性表明，这两种最活跃的CFS有许多共同的特征，而且CFS及其相关基因可能是细胞生存所必需的。(C)2002 Wiley-Liss，Inc.
Recently, several common fragile sites (CFSs) have been cloned and characterized, including the two most frequently observed in the human population, FRA3B and FRA16D. In addition to their high frequency of breakage, FRA3B and FRA16D colocalize with genes crossing large regions of breakage. At FRA3B, the fragile histidine triad (FHIT) gene spans more than 1 Mb, and at FRA16D, the WWOX gene spans more than 750 kb. It has also been shown that in Mus musculus, a CFS Fra 14A2 and the mouse Fhit gene are conserved in the orthologous region of the genome. In this study, we positioned the ortholog to WWOX (Wox1) at chromosome band 8E1 in the mouse genome. To determine whether, like FraI4A2 and Fhit Fra8EI and Wox1 colocalized in the mouse, we prepared bacterial and yeast artificial chromosome probes, and we hybridized them to aphidicolin-treated mouse metaphase chromosomes. Our data demonstrate that WoxI colocalizes with Fra8E1. Furthermore, the sequence from this region, including introns, is highly conserved over at least a 100-kb region. This evolutionary conservation suggests that the two most active CFSs share many features, and that CFSs and their associated genes may be necessary for cell survival. (C) 2002 Wiley-Liss, Inc.