A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species

A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species
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DOI:
10.1073/pnas.0707640104
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发表时间:
2007-10-02
影响因子:
11.1
通讯作者:
Fairbanks, Lynn A.
Fairbanks, Lynn A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Freimer, Nelson B.;Service, Susan K.;Fairbanks, Lynn A.

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非人类灵长类动物 (NHP) 提供了重要的研究模型。它们与人类的强烈相似性使它们对于理解复杂的行为特征以及大脑结构和功能特别有价值。我们在这里报告了 NHP 神经系统生物学特征的遗传图谱,即氯巴明代谢物高香草酸 (HVA) 的脑脊液 (CSF) 浓度,在一个扩展的近交黑长尾猴 (Chlorocebus aethiops sabaeus) 谱系中。 CSF HVA 是 CNS 多巴胺活性的一个指标,据推测,它对 NHP 和人类的行为变化有很大影响。对于数量性状基因座(QTL)作图,我们进行了两阶段程序。我们首先使用短串联重复标记的第一代遗传图谱扫描了基因组。随后,利用基因组扫描确定的最有希望区域内的> 100个SNP,我们将CSF HVA的QTL在全基因组显着性水平(比值得分的峰值对数> 4)映射到一个狭窄的明确划分的区间(
Non-human primates (NHP) provide crucial research models. Their strong similarities to humans make them particularly valuable for understanding complex behavioral traits and brain structure and function. We report here the genetic mapping of an NHP nervous system biologic trait, the cerebrospinal fluid (CSF) concentration of the clopamine metabolite homovanillic acid (HVA), in an extended inbred vervet monkey (Chlorocebus aethiops sabaeus) pedigree. CSF HVA is an index of CNS dopamine activity, which is hypothesized to contribute substantially to behavioral variations in NHP and humans. For quantitative trait locus (QTL) mapping, we carried out a two-stage procedure. We first scanned the genome using a first-generation genetic map of short tandem repeat markers. Subsequently, using >100 SNPs within the most promising region identified by the genome scan, we mapped a QTL for CSF HVA at a genome-wide level of significance (peak logarithm of odds score >4) to a narrow well delineated interval (