Péterfy M, Gyuris T, Antonio L, Takács L
Department of Biomedical Science, Amgen Inc., Thousand Oaks, CA 91320-1789, USA.
Gene. 1998 Aug 31;216(2):225-31. doi: 10.1016/s0378-1119(98)00321-7.
Isolated lissencephaly sequence and Miller-Dieker syndrome are related neurodevelopmental disorders caused by defects of the LIS1 gene encoding the alpha subunit of intracellular platelet-activating factor acetylhydrolase. In addition to the ortholog of the human LIS1 gene (Pafaha/Lis1), the mouse genome contains two more homologs. In order to characterize the new members of this gene family, we isolated both Pafaha/Lis1-related genes (Pafaha-ps1 and Pafaha-ps2) from a mouse genomic library. Pafaha-ps1 and Pafaha-ps2 are processed pseudogenes formed by the retroinsertion of 5'-truncated Pafaha/Lis1 cDNAs. Sequence analysis revealed a striking accumulation of retroelements at both loci, identifying two retroinsertion hotspots in the mouse genome. The recognition of tRNA genes flanking Pafaha-ps1 provides an example for the potential association of RNA polymerase III transcription and retroinsertion in mammals. Linkage mapping placed Pafaha-ps1 and Pafaha-ps2 to distal chromosome (Chr) 3 and proximal Chr 7, respectively. Our results indicate that only one of the three LIS1-related mouse loci (Pafaha/Lis1) is functional, in contrast with two closely related functional genes (LIS1 and LIS2) reported in humans. 1998 Elsevier Science B.V.
孤立性无脑回序列征和米勒-迪克尔综合征是由编码细胞内血小板活化因子乙酰水解酶α亚基的LIS1基因缺陷引起的相关神经发育障碍。除了人类LIS1基因的直系同源基因（Pafaha/Lis1）外，小鼠基因组还包含另外两个同源基因。为了表征该基因家族的新成员，我们从小鼠基因组文库中分离出了两个与Pafaha/Lis1相关的基因（Pafaha-ps1和Pafaha-ps2）。Pafaha-ps1和Pafaha-ps2是由5'端截短的Pafaha/Lis1 cDNA反转录插入形成的加工假基因。序列分析显示这两个位点都有大量反转录元件积累，确定了小鼠基因组中的两个反转录插入热点。对Pafaha-ps1侧翼tRNA基因的识别为哺乳动物中RNA聚合酶III转录与反转录插入的潜在关联提供了一个例子。连锁图谱分别将Pafaha-ps1和Pafaha-ps2定位到远端染色体3和近端染色体7。我们的结果表明，与人类报道的两个密切相关的功能基因（LIS1和LIS2）不同，三个与LIS1相关的小鼠基因座中只有一个（Pafaha/Lis1）具有功能。1998爱思唯尔科学出版社B.V.
