Single-minded—Two Genes, Three Chromosomes
- Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21210
This extract was created in the absence of an abstract.
Comparative sequence and expression analyses of homologous genes from different species allow us to infer their conserved or divergent gene function. This is highlighted by the comparison of thesingle-minded (sim) genes, which have been identified in Drosophila (Crews et al. 1988; Thomas et al. 1988), mouse (Ema et al. 1996; Fan et al. 1996; Moffett et al. 1996; Yamaki et al. 1996), and now in human (Chrast et al., this issue). Decipheringsim gene function is of particular interest because of its importance in the development of the central nervous system (CNS), and the potential involvement of one of the two human SIM genes in the pathogenesis of Down syndrome (DS).
DS is the most frequent genetic cause of mental retardation. Although most cases of DS are attributable to the presence of three full copies of chromosome 21, rare DS patients carry chromosomal rearrangements resulting in triplication of only part of chromosome 21. Molecular characterization of these “partial trisomy” cases has allowed the delineation of a DS critical region (DSCR), located at the sub-band 21q22.2, which correlates with many DS abnormalities (Delabar et al. 1993). Several laboratories have characterized and cloned the DSCR. Using the exon-trapping technique to isolate potential coding sequences within this region, two groups have identified exons that predict an open reading frame that is highly homologous to the Drosophila sim gene product (Chen et al. 1995; Dahmane et al. 1995). In parallel, two murine homologs of sim have been cloned and named Sim1 and Sim2 (Ema et al. 1996; Fan et al. 1996; Moffett et al. 1996; Yamaki et al. 1996). Chrast et al. (this issue) now report the cloning of human SIM1 and SIM2cDNAs. Based on its chromosomal location and sequence, the gene that …
