A 2-Mb sequence-ready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2

A 2-Mb sequence-ready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2
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DOI:
10.1006/geno.1999.6001
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发表时间:
1999-12-01
期刊:
影响因子:
4.4
通讯作者:
Ohki, M
Ohki, M
中科院分区:
生物学3区
文献类型:
--
作者:
Gomyo, H;Arai, Y;Ohki, M

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人类染色体11q23.2已被认为含有肿瘤抑制基因,其缺失与肺癌和乳腺癌以及神经母细胞瘤相关。为了分析基因组结构并从该区域分离候选抑癌基因,我们使用噬菌体P1(P1)、细菌人工染色体(BAC)和P1衍生的人工染色体(PAC)构建了一个2-Mb序列准备好的重叠群图谱。该图谱包括24个重叠P1、BAG和PAC克隆的重叠群。为了从该区域分离基因片段,我们使用P1、BAG和PAC克隆进行了直接cDNA文库筛选、外显子捕获、EST作图和基因组测序。5个克隆的序列分析,其中跨越23%(458,738 bp)的区域,并广泛的基因扫描沿着整个区域显示,该地区是非常稀缺的基因,但我们确定了一个普遍表达的新基因和一个睾丸特异性基因片段。我们称之为IGSF 4(免疫球蛋白超家族4)的新基因转录成1.6或4.4 kb的RNA,编码442个氨基酸的蛋白质。它与小鼠IGSF-B12和细胞粘附分子NCAM 1和NCAM 2在其Ig样Ca型结构域内具有很强的同源性。IGSF 4基因是一个新发现的位于常见杂合性缺失区的基因,具有许多有趣的特征,可能是肿瘤抑制基因的候选基因。(C)北京:科学出版社.
Human chromosome 11q23.2 has been proposed to contain a tumor suppressor gene(s) whose deletion has been associated with cancer of the lung and breast and with neuroblastoma. To analyze the genomic structure and to isolate a candidate tumor suppressor gene from this region, we constructed a 2-Mb sequence-ready contig map using bacteriophage P1 (P1), bacterial artificial chromosome (BAC), and P1-derived artificial chromosome (PAC). The map comprises a contig of 24 overlapping P1, BAG, and PAC clones. To isolate gene fragments from the region, we performed direct cDNA library screening, exon trapping, EST mapping, and genomic sequencing using the P1, BAG, and PAC clones. Sequence analysis of 5 clones, which spans 23% (458,738 bp) of the region, and extensive gene scanning along the entire region revealed that the region is extraordinarily scarce in genes, but we identified one ubiquitously expressed novel gene and one testis-specific gene fragment. The novel gene, which we call IGSF4 (immunoglobuIin superfamily 4), is transcribed into a 1.6- or 4.4-kb RNA encoding a 442-amino-acid protein. It shares strong homology with mouse IGSF-B12 and cell adhesion molecules NCAM1 and NCAM2 within their Ig-like Ca-type domains. The IGSF4 gene, a novel gene that is shown to be located in the common loss of heterozygosity region, possesses a number of interesting features and may be good candidate for a tumor suppressor gene. (C) 1999 Academic Press.