Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21.
Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21.
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DOI：
10.1073/pnas.78.1.405
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发表时间：
1981
影响因子：
11.1
通讯作者：
D. Patterson;S. Graw;C. Jones
中科院分区：
文献类型：
--
作者：
D. Patterson;S. Graw;C. Jones
提出了一种确定哺乳动物细胞协调遗传调控的方法。该方法包括：(I)分离一组在相关途径中有缺陷的突变体；(Ii)对这些突变体进行互补分析，以确定显性，并将突变体分类为各种不同的互补组；(Iii)确定突变体中的生化块；(Iv)鉴定未能补充至少两个相互补充的不同互补组成员的个别突变体，这些突变体据说显示受影响功能的协调调节；(V)相关细胞类型的生化和逆转分析，以确认观察到的协调调节的基础；(Vi)将单个基因分配给特定的人类染色体；(Vii)绘制基因图谱，以确定基因组上的邻接性；以及()检查相关基因产物的结构。该方法证实了在我们的Ade-C突变体中缺陷的磷酸核糖基甘油酰胺合成酶[5-磷酸核糖胺：甘氨酸连接酶(ADP形成)，EC 6.3.4.13]和在我们的Ade-G突变体中缺陷的磷酸核糖基氨基咪唑合成酶[5‘-磷酸核糖基甲酰甘氨双胺环合酶(ADP形成)，EC 6.3.3.1]之间的协调调节。此外，这两个基因都可以分配到人类21号染色体上。因为现在至少有两个嘌呤生物合成基因被分配到21号染色体上，而且21三体(唐氏综合征)患者的血清嘌呤水平增加，这可能是这些患者的细胞过度生产嘌呤，这种过度生产可能与该综合征的病理相关。
A method for determining coordinate genetic regulation is proposed for mammalian cells. The method involves (i) isolation of a set of mutants defective in the relevant pathway; (ii) complementation analysis of these mutants to determine dominance and to categorize the mutants into various different complementation groups; (iii) determination of the biochemical blocks in the mutants; (iv) identification of individual mutants that fail to complement the members of at least two distinct complementation groups that complement each other, such mutants being said to show coordinate regulation of the affected functions; (v) biochemical and reversion analysis of the relevant cell types to confirm the basis for the observed coordinate regulation; (vi) assignment of the individual genes to particular human chromosomes; (vii) mapping of the genes to determine contiguity on the genome; and (viii) examination of the structure of the relevant gene products. This method has allowed the demonstration of coordinate regulation between the gene coding for phosphoribosylglycineamide synthetase [5-phosphoribosylamine:glycine ligase (ADP-forming), EC 6.3.4.13], defective in our Ade-C mutants, and the gene coding for phoshoribosylaminoimidazole synthetase [5'-phosphoribosylformylglycinamidine cyclo-ligase (ADP-forming), EC 6.3.3.1], defective in our Ade-G mutants. Moreover, both genes can be assigned to human chromosome 21. Because at least two genes for purine biosynthesis have now been assigned to chromosome 21, and because patients with trisomy 21 (Down syndrome) show increased levels of serum purines, it may be that cells of these patients overproduce purines and that this overproduction may be relevant to the pathology of the syndrome.