GENETIC AND BIOCHEMICAL STUDY OF HUMAN CHROMOSOME 21

人类 21 号染色体的遗传和生物化学研究

• 批准号: 3322533
• 负责人: DAVID PATTERSON
• 金额: $ 9.7万
• 依托单位: ELEANOR ROOSEVELT INST FOR CANCER RES
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3322533
• 关键词: Downs syndrome; acyltransferase; chromosomes; complementary DNA; gel electrophoresis; genetic library; genetic manipulation; genetic mapping; genetic markers; human genetic material tag; human tissue; laboratory rabbit; laboratory rat; ligase; linkage mapping; molecular genetics; nucleic acid probes; nucleic acid sequence; purine /pyrimidine metabolism; purines; trisomy

Down Syndrome (Trisomy 21) is the most common genetic cause of major mental retardation in the United States and a significant cause of congenital heart disease and spontaneous abortion. Down syndrome individuals are at increased risk for diseases which occur in the general population such as leukemia and premature aging of the Alzheimer's type. Down Syndrome patients have been found to be hyperuricemic, and evidence indicating that this is due to purine overproduction has been obtained. We have shown that at least 2 of the enzymes coding for purine biosynthesis are coded for by genes on chromosome 21. We have purified one of these, phosphoribosylglycineamide synthetase (GARS), to apparent homogeneity from rat liver and prepared antibody to it. We have also shown that in Drosophila the genes for GARS and for phosphoribosylaminoimidazole synthetase (AIRS) also on chromosome 21 in humans, are on the same cloned DNA sequence as the gene for phosphoribosylglycineamide formyltransferase (GART) cloned by Dr. S. Henikoff. We now propose 1) to determine whether the elevated purine levels seen in Down syndrome patients are related to the presence of these genes on chromosome 21 and to the pathology of Down Syndrome, and 2) to use the unique genetic system afforded by the locations of the genes for enzymes of purine synthesis on chromosome 21 to understand the nature of the pathogenetic region on chromosome 21, whether or not purine synthesis is related directly to the observed pathology. Specific aims include characterization of the enzymes of purine synthesis coded for by genes on chromosome 21 and isolation and characterization of the genes themselves, determination of whether rate of purine synthesis varies according to chromosome 21 content, and the creation of a detailed retriction enzyme and physical linkage map of the region of chromsosome 21 important for Down Syndrome, using the genes for enzymes of purine synthesis as a starting point.

唐氏综合征（21三体）是最常见的遗传性主要精神疾病的原因。 在美国的一个重要原因是先天性发育迟缓， 心脏病和自然流产。 唐氏综合症患者在 增加普通人群发生疾病的风险，例如 白血病和老年痴呆症的早衰。 唐氏综合症 已发现患者患有高尿酸血症，有证据表明 这是由于嘌呤的过量产生。 我们已经证明 编码嘌呤生物合成的酶中的至少2种由以下编码： 21号染色体上的基因 我们净化了其中一个， 磷酸核糖基甘氨酸酰胺合成酶（加尔斯），从 并制备了抗鼠肝纤维化的抗体。 果蝇的加尔斯和磷酸核糖氨基咪唑基因 合成酶（AIRS）也在人类21号染色体上， 作为磷酸核糖基甘氨酸酰胺甲酰基转移酶基因的DNA序列 （GART）由S.赫尼科夫 我们现在建议1）确定是否 在唐氏综合征患者中观察到的升高的嘌呤水平与 这些基因在21号染色体上的存在和唐氏症的病理学 综合征，以及2）使用由位置提供的独特遗传系统 嘌呤合成酶的基因， 21号染色体上致病区域的性质， 嘌呤合成与观察到的病理学直接相关。 具体 目的包括表征编码嘌呤合成的酶， 通过21号染色体上的基因以及基因的分离和表征 它们本身，确定嘌呤合成的速率是否变化 根据染色体21的内容，并创建一个详细的 21号染色体区域的限制酶和物理连锁图谱 对唐氏综合症很重要，利用嘌呤酶的基因 综合作为起点。

项目成果

Somatic cell genetic approaches to Down's syndrome.

唐氏综合症的体细胞遗传学方法。

• DOI: 10.1111/j.1749-6632.1982.tb26844.x
• 发表时间: 1982
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Patterson,D;Jones,C;Scoggin,C;Miller,YE;Graw,S
• 通讯作者: Graw,S

Two Drosophila melanogaster mutations block successive steps of de novo purine synthesis.

• DOI: 10.1073/pnas.83.11.3919
• 发表时间: 1986-06
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: S. Henikoff;D. Nash;R. Hards;J. Bleskan;J. Woolford;F. Naguib;D. Patterson

Fractionation of large mammalian DNA restriction fragments using vertical pulsed-field gradient gel electrophoresis.

使用垂直脉冲场梯度凝胶电泳对大型哺乳动物 DNA 限制性片段进行分级分离。

• DOI: 10.1007/bf01560665
• 发表时间: 1986
• 期刊: Somatic cell and molecular genetics
• 作者: Gardiner,K;Laas,W;Patterson,D
• 通讯作者: Patterson,D

Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21.

• DOI: 10.1073/pnas.78.1.405
• 发表时间: 1981
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: D. Patterson;S. Graw;C. Jones

Measurement of glycinamide ribonucleotide synthetase activity in intact human fibroblasts and Chinese hamster ovary cells.

完整人成纤维细胞和中国仓鼠卵巢细胞中甘氨酰胺核糖核苷酸合成酶活性的测量。

• DOI: 10.1159/000469333
• 发表时间: 1986
• 期刊: Enzyme
• 作者: Hards,RG;Patterson,D
• 通讯作者: Patterson,D