Comparative sequence analysis of a region on human chromosome 13q14, frequently deleted in B-cell chronic lymphocytic leukemia, and its homologous region on mouse chromosome 14

Comparative sequence analysis of a region on human chromosome 13q14, frequently deleted in B-cell chronic lymphocytic leukemia, and its homologous region on mouse chromosome 14
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DOI:
10.1006/geno.2000.6386
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发表时间:
2000-12-15
期刊:
影响因子:
4.4
通讯作者:
Sangfelt, O
Sangfelt, O
中科院分区:
生物学3区
文献类型:
--
作者:
Kapanadze, B;Makeeva, N;Sangfelt, O

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以前的研究表明,在人类染色体13 q14上存在一个假定的肿瘤抑制基因,该基因通常在B细胞慢性淋巴细胞白血病(B-CLL)患者中缺失。我们最近发现了一个最小的缺失区域,包括两个相邻基因的部分,称为LEU 1和LEU 2(白血病相关基因1和2),和几个额外的转录本。此外,在该区域的50 kb着丝粒处,我们已经鉴定了另一个基因,LEU 5/RFP 2。为了进一步阐明这一区域复杂的基因组结构,我们已经确定,映射,并在小鼠中的同源区域测序。荧光原位杂交分析表明,该区域映射到小鼠14号染色体。发现该区域的整体组织和基因顺序在小鼠中高度保守。人缺失热点区与其同源小鼠区之间的序列比较显示了高度的序列保守性,总体评分为74%。然而,我们的数据也表明,在转录序列方面,只有两个,人LEU 2和LEU 5/RFP 2,是明显保守的,加强了这些基因作为推定的候选B-CLL肿瘤抑制基因的情况。(C)北京大学出版社.
Previous studies have indicated the presence of a putative tumor suppressor gene on human chromosome 13q14, commonly deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). We have recently identified a minimally deleted region encompassing parts of two adjacent genes, termed LEU1 and LEU2 (leukemia-associated genes 1 and 2), and several additional transcripts. In addition, 50 kb centromeric to this region we have identified another gene, LEU5/RFP2. To elucidate further the complex genomic organization of this region, we have identified, mapped, and sequenced the homologous region in the mouse. Fluorescence in situ hybridization analysis demonstrated that the region maps to mouse chromosome 14. The overall organization and gene order in this region were found to be highly conserved in the mouse. Sequence comparison between the human deletion hotspot region and its homologous mouse region revealed a high degree of sequence conservation with an overall score of 74%. However, our data also show that in terms of transcribed sequences, only two of those, human LEU2 and LEU5/RFP2, are clearly conserved, strengthening the case for these genes as putative candidate B-CLL tumor suppressor genes. (C) 2000 Academic Press.