Gejman P V, Ram A, Gelernter J, Friedman E, Cao Q, Pickar D, Blum K, Noble E P, Kranzler H R, O'Malley S
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, Md. 20892.
JAMA. 1994 Jan 19;271(3):204-8.
To examine the dopamine D2 receptor (DRD2) gene coding sequences for abnormalities associated with schizophrenia or alcoholism and thereby help to resolve the controversy surrounding the reported association of alcoholism with a restriction fragment length polymorphism located close to the DRD2 gene.
Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient gel electrophoresis followed by direct nucleotide sequencing of detected variants.
Patients and controls from clinical and epidemiologic collections in the United States and Europe.
A total of 253 unrelated individuals, including 106 patients with schizophrenia, 113 with alcoholism, and 34 controls. For alcoholism we included patients from previously published series in which an association of illness with allele A1 was reported (Taql site 3' to the DRD2 gene) and from other published series in which nonconfirmations of this association were reported. Nearly all persons examined were white.
Frequency of nonsilent variations in DRD2 gene DNA sequences in the different diagnostic groups.
We found three infrequent DNA variants that predict altered amino acid sequence of the receptor. None of these is associated with either alcoholism or schizophrenia.
No structural coding abnormalities in the DRD2 gene are present in alcoholism or schizophrenia.
检测多巴胺D2受体（DRD2）基因编码序列中与精神分裂症或酒精中毒相关的异常情况，从而有助于解决围绕酒精中毒与位于DRD2基因附近的限制性片段长度多态性之间报道关联的争议。
通过变性梯度凝胶电泳对完整的DRD2基因编码序列进行突变分析，随后对检测到的变异体进行直接核苷酸测序。
美国和欧洲临床及流行病学研究中的患者和对照。
总共253名无亲属关系的个体，包括106名精神分裂症患者、113名酒精中毒患者和34名对照。对于酒精中毒患者，我们纳入了先前发表系列研究中的患者（其中报道了疾病与A1等位基因的关联，位于DRD2基因3'端的Taql位点）以及其他发表系列研究中报道该关联未得到证实的患者。几乎所有接受检查的人均为白人。
不同诊断组中DRD2基因DNA序列中非同义变异的频率。
我们发现了三个罕见的DNA变异体，它们预测受体的氨基酸序列会发生改变。这些变异体均与酒精中毒或精神分裂症无关。
酒精中毒或精神分裂症患者的DRD2基因不存在结构编码异常。
