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首页> 外文期刊>Genomics >The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome.
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The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome.

机译：ZNF198的基因组结构和t（8; 13）骨髓增生综合征的断点位置。

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The t(8;13)(p11;q12) is the most common translocation associated with the 8p11 myeloproliferative syndrome and results in an identical mRNA fusion between ZNF198 at 13q12 and FGFR1 at 8p11 in all cases thus far reported. ZNF198 is a widely expressed gene that is predicted to encode a 1377-amino-acid protein with five Zn finger-related motifs known as MYM domains. To determine the genomic DNA structure of ZNF198, we employed bubble PCR from PAC clones with a panel of gene-specific primers. Sequencing of these products revealed that ZNF198 consists of 26 exons with the initiation codon located in exon 4. The t(8;13) results in a consistent mRNA fusion of ZNF198 exon 17 to FGFR1 exon 9. Notable features of the structure of ZNF198 include three noncanonical GC donor splice sites and the presence of an alternatively spliced intron within exon 4. Amplification of genomic DNA from six t(8;13) patients with primers to ZNF198 exon 17 and FGFR1 exon 9 yielded patient-specific products ranging in size from 500 bp to 2.5 kb, indicating that the positions of the breakpoints in the t(8;13) are tightly clustered. The positions of the six t(8;13) breakpoints were determined and found to be distributed across ZNF198 intron 17 and FGFR1 intron 8 with no apparent subclustering. No consistent sequence motifs, repeats, or topoisomerase II cleavage sites were found at or near the breakpoints. It remains unclear why the t(8;13) translocation breakpoints occur within such small genomic regions, and it is possible that strict ZNF198-FGFR1 coding requirements restrict the positions of the breakpoints. Copyright 1999 Academic Press.
机译：t（8; 13）（p11; q12）是与8p11骨髓增生综合征相关的最常见易位，在迄今为止报道的所有情况下，导致13q12处的ZNF198和8p11处的FGFR1之间的mRNA融合相同。 ZNF198是一种广泛表达的基因，预计可编码具有5个Zn手指相关基序的1377个氨基酸蛋白，称为MYM结构域。为了确定ZNF198的基因组DNA结构，我们使用了带有一组基因特异性引物的PAC克隆的泡沫PCR。这些产物的测序表明，ZNF198由26个外显子组成，起始密码子位于外显子4。t（8; 13）导致ZNF198外显子17与FGFR1外显子9的mRNA融合一致。ZNF198结构的显着特征包括三个非规范GC供体剪接位点，以及在外显子4中存在一个剪接的内含子。使用ZNF198外显子17和FGFR1外显子9的引物扩增6例t（8; 13）患者的基因组DNA，可产生患者特异性产物，大小从500 bp至2.5 kb，表明t（8; 13）中的断点位置紧密聚集。确定了六个t（8; 13）断点的位置，发现它们分布在ZNF198内含子17和FGFR1内含子8之间，没有明显的亚簇。在断点处或附近没有发现一致的序列基序，重复或拓扑异构酶II切割位点。尚不清楚为什么在如此小的基因组区域内会出现t（8; 13）易位转折点，并且严格的ZNF198-FGFR1编码要求可能会限制转折点的位置。版权所有1999 Academic Press。

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