Lichter J B, Barr C L, Kennedy J L, Van Tol H H, Kidd K K, Livak K J
Du Pont Merck Pharmaceutical Company, Experimental Station, Wilmington, DE 19880-0328.
Hum Mol Genet. 1993 Jun;2(6):767-73. doi: 10.1093/hmg/2.6.767.
The human dopamine D4 receptor contains a novel polymorphism within the putative third cytoplasmic loop of the protein. The polymorphism is characterized by a varying number of direct imperfect 48-bp repeats in the gene. Pharmacological characterization has suggested that this receptor is the site through which the atypical neuroleptic clozapine exerts its antipsychotic action and that some polymorphic variants display different pharmacological properties. Further analysis of the repeat region using innovative technologies indicates that the alleles vary not only in the number of repeats (2-8 or 10 repeat units) but also in the sequence of the repeats and the order in which they appear. In 178 unrelated chromosomes we have identified 19 different repeats in 25 different haplotypes coding for 18 different predicted amino acid sequences, making this one of the most variable functional proteins currently described.
人类多巴胺D4受体在该蛋白质假定的第三个细胞质环内存在一种新型多态性。这种多态性的特征是基因中存在数量可变的直接不完全48碱基对重复序列。药理学特征表明，该受体是非典型抗精神病药物氯氮平发挥其抗精神病作用的位点，并且一些多态性变体表现出不同的药理学特性。使用创新技术对重复区域进行的进一步分析表明，等位基因不仅在重复次数（2 - 8或10个重复单元）上有所不同，而且在重复序列的顺序以及它们出现的顺序上也有所不同。在178条不相关的染色体中，我们在25种不同的单倍型中鉴定出了19种不同的重复序列，这些单倍型编码18种不同的预测氨基酸序列，这使得它成为目前所描述的最具变异性的功能蛋白之一。
