de Bruijn D R, Kater-Baats E, Eleveld M, Merkx G, Geurts Van Kessel A
Department of Human Genetics, University Medical Center, St. Radboud, Nijmegen, The Netherlands.
Cytogenet Cell Genet. 2001;92(3-4):310-9. doi: 10.1159/000056920.
We have previously isolated and characterized a mouse cDNA orthologous to the human synovial sarcoma associated SS18 (formerly named SSXT and SYT) cDNA. Here, we report the characterization of the genomic structure of the mouse Ss18 gene. Through in silico methods with sequence information contained in the public databases, we did the same for the human SS18 gene and two human SS18 homologous genes, SS18L1 and SS18L2. In addition, we identified a mouse Ss18 processed pseudogene and mapped it to chromosome 1, band A2-3. The mouse Ss18 gene, which is subject to extensive alternative splicing, is made up of 11 exons, spread out over approximately 45 kb of genomic sequence. The human SS18 gene is also composed of 11 exons with similar intron-exon boundaries, spreading out over about 70 kb of genomic sequence. One alternatively spliced exon, which is not included in the published SS18 cDNA, corresponds to a stretch of sequence which we previously identified in the mouse Ss18 cDNA. The human SS18L1 gene, which is also made up of 11 exons with similar intron-exon boundaries, was mapped to chromosome 20 band q13.3. The smaller SS18L2 gene, which is composed of three exons with similar boundaries as the first three exons of the other three genes, was mapped to chromosome 3 band p21. Through sequence and mutation analyses this gene could be excluded as a candidate gene for 3p21-associated renal cell cancer. In addition, we created a detailed BAC map around the human SS18 gene, placing it unequivocally between the CA-repeat marker AFMc014wf9 and the dihydrofolate reductase pseudogene DHFRP1. The next gene in this map, located distal to SS18, was found to be the TBP associated factor TAFII-105 (TAF2C2). Further analogies between the mouse Ss18 gene, the human SS18 gene and its two homologous genes were found in the putative promoter fragments. All four promoters resemble the promoters of housekeeping genes in that they are TATA-less and embedded in canonical CpG islands, thus explaining the high and widespread expression of the SS18 genes.
我们之前已分离并鉴定出一个与人类滑膜肉瘤相关的SS18（原名为SSXT和SYT）cDNA直系同源的小鼠cDNA。在此，我们报告小鼠Ss18基因基因组结构的特征。通过利用公共数据库中包含的序列信息进行电子分析方法，我们对人类SS18基因以及两个人类SS18同源基因SS18L1和SS18L2也进行了同样的分析。此外，我们鉴定出一个小鼠Ss18加工假基因，并将其定位到1号染色体A2 - 3带。小鼠Ss18基因存在广泛的可变剪接，由11个外显子组成，分布在约45 kb的基因组序列上。人类SS18基因也由11个外显子组成，具有相似的内含子 - 外显子边界，分布在约70 kb的基因组序列上。一个可变剪接外显子（未包含在已发表的SS18 cDNA中）对应于我们之前在小鼠Ss18 cDNA中鉴定出的一段序列。人类SS18L1基因也由11个外显子组成，具有相似的内含子 - 外显子边界，被定位到20号染色体q13.3带。较小的SS18L2基因由三个外显子组成，其边界与其他三个基因的前三个外显子相似，被定位到3号染色体p21带。通过序列和突变分析，该基因可被排除作为3p21相关肾细胞癌的候选基因。此外，我们创建了人类SS18基因周围的详细BAC图谱，明确将其定位在CA重复标记AFMc014wf9和二氢叶酸还原酶假基因DHFRP1之间。该图谱中位于SS18远端的下一个基因被发现是TBP相关因子TAFII - 105（TAF2C2）。在假定的启动子片段中发现了小鼠Ss18基因、人类SS18基因及其两个同源基因之间的进一步相似性。所有四个启动子都类似于管家基因的启动子，因为它们没有TATA盒且嵌入典型的CpG岛中，从而解释了SS18基因的高表达和广泛表达。
