Palmer Abraham A, Breen Laura L, Flodman Pamela, Conti Lisa H, Spence M Anne, Printz Morton P
Department of Pharmacology, University of California San Diego, La Jolla 92093, USA.
Psychopharmacology (Berl). 2003 Jan;165(3):270-9. doi: 10.1007/s00213-002-1258-0. Epub 2002 Nov 9.
Schizophrenia is a common and debilitating psychiatric disorder that is partially under genetic control. Because of difficulties in mapping the genes that influence susceptibility to schizophrenia in humans, there has been substantial interest in mapping genes that control endophenotypes for schizophrenia in both human and rodent populations. Deficient prepulse inhibition (PPI) of the startle response has shown promise as an endophenotype for schizophrenia, as well as several other psychiatric disorders.
Brown Norway (BN/SsNHsd) and Wistar Kyoto (WKY/lj-cr) rats were used because they show a large, unconfounded difference in PPI. We used interval mapping methods to identify quantitative trait loci (QTL) for PPI in a backcross population.
We identified a QTL on chromosome 2 with a LOD score of 3.63 and a suggestive QTL on chromosome 18 with a LOD score of 2.71.
Both of the identified regions contain several candidate genes. Furthermore, the implicated rat chromosomes are syntenic with human chromosomal regions that have been reported to contain QTL for schizophrenia, bipolar disorder, and Tourette's syndrome. These results identify the chromosomal location of gene(s) that modulate an endophenotype for schizophrenia, and other psychiatric disorders, and may provide a shortcut to identifying specific genes and/or biochemical pathways involved in human psychiatric diseases.
精神分裂症是一种常见且使人衰弱的精神疾病，部分受基因控制。由于难以定位影响人类精神分裂症易感性的基因，人们对在人类和啮齿动物群体中定位控制精神分裂症内表型的基因产生了浓厚兴趣。惊吓反应的前脉冲抑制（PPI）缺陷已显示出有望作为精神分裂症以及其他几种精神疾病的内表型。
使用了挪威棕色大鼠（BN/SsNHsd）和威斯塔京都大鼠（WKY/lj-cr），因为它们在PPI上表现出巨大且无混淆的差异。我们使用区间定位方法在回交群体中鉴定PPI的数量性状基因座（QTL）。
我们在2号染色体上鉴定出一个LOD分数为3.63的QTL，在18号染色体上鉴定出一个LOD分数为2.71的提示性QTL。
两个已鉴定区域都包含几个候选基因。此外，涉及的大鼠染色体与据报道含有精神分裂症、双相情感障碍和抽动秽语综合征QTL的人类染色体区域是同线的。这些结果确定了调节精神分裂症和其他精神疾病内表型的基因的染色体位置，并可能为鉴定涉及人类精神疾病的特定基因和/或生化途径提供一条捷径。
