C21orf5, a novel human chromosome 21 gene, has a Caenorhabditis elegans ortholog (pad-1) required for embryonic patterning

To contribute to the development of the transcription map of human chromoso me 21 (HC21), we isolated a new transcript, C21orf5 (chromosome 21 open rea ding frame 5), encoding a predicted 2298-amino-acid protein. Analysis of th e genomic DNA sequence revealed that C21orf5 consists of 37 exons that exte nd over 130 kb and maps between the CBR3 (carbonyl reductase 3) and the KIA A0136 genes. Northern blot analyses showed a ubiquitously expressed RNA spe cies of 8.5 kb. RNA in situ hybridization on brain sections of normal human embryos revealed a strong labeling in restricted areas of the cerebral cor tex. In silico analysis of the deduced C21orf5 protein revealed several hig hly probable transmembrane segments but no known protein domains or homolog y with known proteins. However, there were significant homologies to severa l hypothetical Caenorhabditis elegans proteins and Drosophila melanogaster genomic sequences. To investigate the function of C21orf5, we isolated the cDNA of the C. elegans ortholog and performed double-stranded RNA-mediated genetic interference experiments. The major phenotype observed in the proge ny of injected animals was embryonic lethality. Most of the tissues of the embryo failed to undergo proper patterning during gastrulation, and morphog enesis did not occur; thus we termed the ortholog pad-1, for patterning def ective 1. These results indicated that pad-1 is essential for the developme nt and the survival of C. elegans. This study provides the first example of the use of C. elegans as a model to study the function of genes on human c hromosome 21 that might be involved in Down syndrome. (C) 2000 Academic Pre ss.