Fechter Anne, Buettel Isabel, Kuehnel Elisabeth, Savelyeva Larissa, Schwab Manfred
Division of Tumour Genetics, German Cancer Research Center, 69120 Heidelberg, Germany.
Genes Chromosomes Cancer. 2007 Jan;46(1):98-106. doi: 10.1002/gcc.20389.
Fragile sites are specific genomic loci that are particularly prone to chromosomal breakage. Based on their incidence in the human population, they are divided into rare fragile sites occurring in less than 5% of all individuals and common fragile sites being a constitutional feature of the genome of probably all individuals. In this study, cloning of unstable DNA sequences, which have been previously genetically tagged with a marker gene, was the basis for defining the genomic localization of the common fragile site FRA11G at 11q23.3. Mapping of the fragile site with six-color fluorescence in situ hybridization (FISH) resulted in the precise genomic localization of FRA11G to a 4.5 Mb region. The chromosomal subband 11q23.3 harbors both the common fragile site FRA11G and the rare fragile site FRA11B. Here, we show that FRA11G maps 0.8 Mb proximal to the genomic region previously defined to be affected by expression of FRA11B; thus, the common and the rare fragile sites at 11q23.3 encompass distinct genomic regions. The region of FRA11G is known to be involved in somatic and germline recurrent aberrations, and it is conceivable that genetic damage resulting from this fragile site might contribute to clinical phenotypes.
脆性位点是特定的基因组位点,特别容易发生染色体断裂。根据它们在人群中的发生率,可分为在所有个体中发生率低于5%的罕见脆性位点和可能是所有个体基因组的一种固有特征的常见脆性位点。在本研究中,对先前已用标记基因进行遗传标记的不稳定DNA序列进行克隆,是确定常见脆性位点FRA11G位于11q23.3的基因组定位的基础。用六色荧光原位杂交(FISH)对脆性位点进行定位,结果将FRA11G精确地定位到一个4.5 Mb的区域。染色体亚带11q23.3同时包含常见脆性位点FRA11G和罕见脆性位点FRA11B。在此,我们表明FRA11G位于先前定义为受FRA11B表达影响的基因组区域近端0.8 Mb处;因此,11q23.3处的常见和罕见脆性位点包含不同的基因组区域。已知FRA11G区域与体细胞和种系复发性畸变有关,可以想象,由这个脆性位点导致的遗传损伤可能会导致临床表型。