Stöber G, Nöthen M M, Pörzgen P, Brüss M, Bönisch H, Knapp M, Beckmann H, Propping P
Institute of Human Genetics, University of Bonn, Germany.
Am J Med Genet. 1996 Nov 22;67(6):523-32. doi: 10.1002/(SICI)1096-8628(19961122)67:6<523::AID-AJMG3>3.0.CO;2-I.
The complete coding region of the norepinephrine transporter (NET) gene was systematically screened for genetic variants in 137 unrelated individuals (including 46 probands with bipolar affective disorder and 45 schizophrenic probands, as well as 46 blood donors) using single-strand conformation analysis. We identified 13 DNA sequence variants, among them five missense substitutions. The missense substitutions Val69Ile, Thr99Ile, Val245Ile, Val449Ile, and Gly478Ser are located at putative transmembrane domains (TMD) 1, 2, 4, 9, and 10, respectively. The Thr99Ile substitution is at the 5th position of the putative leucine-zipper in TMD2. In a case-control study distribution of missense substitutions was found to be similar in 103 patients with bipolar affective disorder, in 228 schizophrenia patients and in 187 controls, indicating that presence of these variants is not causally related to major psychiatric diseases. The detection of a highly polymorphic silent 1287G/A polymorphism was utilized to demonstrate biallelic expression of the NET in adult human brain.
采用单链构象分析方法，对137名无亲缘关系的个体（包括46名双相情感障碍先证者、45名精神分裂症先证者以及46名献血者）的去甲肾上腺素转运体（NET）基因的完整编码区进行了系统的基因变异筛查。我们鉴定出13个DNA序列变异，其中5个为错义替换。错义替换Val69Ile、Thr99Ile、Val245Ile、Val449Ile和Gly478Ser分别位于假定的跨膜结构域（TMD）1、2、4、9和10。Thr99Ile替换位于TMD2中假定的亮氨酸拉链的第5位。在一项病例对照研究中，发现在103名双相情感障碍患者、228名精神分裂症患者和187名对照中，错义替换的分布相似，这表明这些变异的存在与主要精神疾病没有因果关系。利用检测到的高度多态性沉默1287G/A多态性来证明NET在成人大脑中的双等位基因表达。
