Characterization and chromosomal mapping of two pseudogenes of the mouse Pafaha/Lis1 gene:: retrointegration hotspots in the mouse genome

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. (C) 1998 Elsevier Science B.V. All rights reserved.