Defects of ribosomal protein genes and human chromosomal disorders.

在蛋白质合成过程中，核糖体作为细胞的翻译机制起着关键作用。核糖体及其组成部分对正常细胞发育至关重要。哺乳动物细胞中核糖体的生物合成需要四种RNA和大约80种不同的蛋白质等摩尔积累。有人可能预测核糖体成分的遗传缺陷会导致人类发育异常。我们对核糖体蛋白（rp）基因缺陷可能导致人类某些染色体疾病的可能性很感兴趣。为了探索这种可能性，我们已经通过使用功能（内含子）rp基因特异性的STSs系统地绘制了估计的80个人类rp基因。我们使用了三种资源进行基于sts的制图；(i) NIGMS人/啮齿动物体细胞杂交面板用于染色体定位；（ii）全基因组辐射杂交面板用于每个基因的精细定位；（iii） CEPH YAC文库用于YAC序列定位。这些结果使我们能够将大多数人类rp基因非常精确地放置在Whitehead/MIT基因组研究中心构建的人类基因组物理图谱上。74个rp基因在染色体上被分配，73个基因在物理图谱上被更精确地定位。除了两条人类染色体（7号和21号）外，所有染色体都至少携带一个rp基因，而19号染色体携带的rp基因数量异常之多（12号）。我们的rp基因图谱可以作为发现可能由rp基因缺失引起的人类疾病的有力工具。

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.