Nöthen M M, Erdmann J, Shimron-Abarbanell D, Propping P
Institute of Human Genetics, University of Bonn, Germany.
Biochem Biophys Res Commun. 1994 Dec 15;205(2):1194-200. doi: 10.1006/bbrc.1994.2792.
Disturbances of serotonergic pathways have been implicated in a wide variety of neuropsychiatric disorders such as depression, anxiety, migraine, and substance abuse. Genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and/or of pharmacogenetic relevance. Genomic samples from 46 unrelated healthy subjects were investigated by single-strand conformation analysis (SSCA) to screen for genetic variation in the human serotonin 1D beta (5-HT1D beta) receptor gene. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as 5' untranslated regions of the 5-HT1D beta gene. Four nucleotide sequence variants were found: a coding mutation in nucleotide position 371 which leads to an amino acid exchange (Phe-->Cys) in position 124 of the receptor protein and three mutations in the 5' flanking region. For all mutations specific PCR-based assays were developed which allow rapid genotyping in populations and families. To our knowledge, the Phe-124-Cys substitution is the first natural occurring molecular variant which has been identified for the 5-HT1D beta receptor so far.
血清素能通路紊乱与多种神经精神疾病有关，如抑郁症、焦虑症、偏头痛和药物滥用。编码血清素受体蛋白的基因中的遗传变异很可能与这些疾病的遗传易感性和/或药物遗传学相关性有关。通过单链构象分析（SSCA）对46名无亲缘关系的健康受试者的基因组样本进行研究，以筛查人类血清素1Dβ（5-HT1Dβ）受体基因的遗传变异。重叠聚合酶链反应（PCR）片段覆盖了5-HT1Dβ基因的整个编码序列以及5'非翻译区。发现了四个核苷酸序列变异：核苷酸位置371处的编码突变导致受体蛋白第124位的氨基酸交换（苯丙氨酸→半胱氨酸），以及5'侧翼区域的三个突变。针对所有突变开发了基于PCR的特异性检测方法，可在人群和家族中进行快速基因分型。据我们所知，苯丙氨酸-124-半胱氨酸替代是迄今为止为5-HT1Dβ受体鉴定出的首个天然存在的分子变体。
