Defects of ribosomal protein genes and human chromosomal disorders.

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The ribosome plays a key role as the translational machinery in the cell during protein synthesis. The ribosome and, therefore, its components are essential for normal cell development. The biosynthesis of ribosomes in mammalian cells requires equimolar accumulation of four RNA species and about 80 different proteins. One might predict that genetic defects in ribosomal components would results in abnormal human development. We are intrigued by the possibility that deficiencies of ribosomal protein (rp) genes might cause certain chromosomal disorders in humans.To explore this possibility, we have been systematically mapping the estimated 80 human rp genes by using STSs specific to the functional (intron-containing) rp genes. We employed three resources for the STS-based mapping ; (i) NIGMS human/rodent somatic cell hybrid panels for the chromosomal assignments, (ii) a whole-genome radiation hybrid panel for fine localization of each gene (iii) CEPH YAC library for YAC-contig mapping. The results have allowed us to place most of the human rp genes quite precisely on the physical map of the human genome constructed at the Whitehead/MIT Center for Genome Research. Seventy-four rp genes were chromosomally assigned and 73 genes were localized more precisely on the physical map. All but two human chromosomes (7 and 21) have been found to carry at least one rp gene, and chromosome 19 has been found to carry an unusually high number of rp genes (12). Our map of rp genes should serve as a powerful tool for finding human diseases that might be caused by rp gene deficiencies.