Defects of ribosomal protein genes and human chromosomal disorders.

核糖体蛋白基因缺陷与人类染色体疾病。

基本信息

批准号：
07807020
负责人：
KENMOCHI Naoya
金额：
$ 1.34万
依托单位：
University of the Ryukyus
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07807020/
关键词：
gene mapping ribosomal proteins chromosomal map human genome human diseases リボソーム蛋白遺伝子ヒト染色体マッピング遺伝病 YAC STS

项目摘要

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.

核糖体在蛋白质合成过程中作为细胞中的翻译机制起关键作用。因此，核糖体以及其成分对于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种和约80种不同蛋白质的等摩尔积累。可以预测，核糖体成分的遗传缺陷会导致人类异常发育。我们对核糖体蛋白（RP）基因的缺陷可能引起人类的某些染色体疾病的可能性，我们对我们很感兴趣。要探索这种可能性，我们通过使用特定于功能（固有子插入）RP基因的STSS系统地绘制了估计的80个人RP基因。我们为基于STS的映射使用了三个资源；（i）用于染色体分配的nigms人/啮齿动物体细胞杂化板，（ii）一个全基因组辐射杂种，用于每个基因（III）CEPH YAC库的精细定位用于YAC-Contig映射。结果使我们能够将大部分人类RP基因完全精确地放在Whitehead/MIT基因组研究中心构建的人类基因组的物理图上。分配了74个RP基因，并更精确地将73个基因定位在物理图上。除两个人类染色体（7和21）以外的所有染色体都至少携带一个RP基因，并且发现19染色体19染色体具有异常高的RP基因（12）。我们的RP基因地图应作为查找可能由RP基因缺陷引起的人类疾病的强大工具。