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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species
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A quantitative trait locus for variation in dopamine metabolism mapped in a primate model using reference sequences from related species

机译：使用相关物种的参考序列在灵长类动物模型中定位多巴胺代谢变化的数量性状位点

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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 dopamine 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 ( < 10 Mb). The SNP discovery exploited conserved segments between human and rhesus macaque reference genome sequences. Our findings demonstrate the potential of using existing primate reference genome sequences for designing high-resolution genetic analyses applicable across a wide range of NHP species, including the many for which full genome sequences are not yet available. Leveraging genomic information from sequenced to nonsequenced species should enable the utilization of the full range of NHP diversity in behavior and disease susceptibility to determine the genetic basis of specific biological and behavioral traits.
机译：非人类灵长类动物（NHP）提供了至关重要的研究模型。它们与人类的强相似之处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作图，即在一个扩展的近交黑长尾猴（Chlorocebus aethiops sabaeus）谱系中的多巴胺代谢高香草酸（HVA）的脑脊液（CSF）浓度。脑脊液HVA是中枢神经系统多巴胺活性的指标，据推测可对NHP和人类的行为变化做出实质性贡献。对于定量性状基因座（QTL）作图，我们进行了两个阶段的程序。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，在通过基因组扫描鉴定的最有希望的区域内使用> 100个SNP，我们将CSF HVA的QTL定位在全基因组范围内的显着水平（赔率峰值的对数> 4）到一个狭窄的良好划分的区间（<10 Mb）。 SNP发现利用了人类和恒河猴参考基因组序列之间的保守区段。我们的发现表明，使用现有的灵长类参考基因组序列来设计适用于广泛NHP物种的高分辨率遗传分析的潜力，包括许多尚未获得完整基因组序列的物种。利用从测序物种到非测序物种的基因组信息，应该能够利用行为和疾病易感性中的全部NHP多样性来确定特定生物学和行为特征的遗传基础。

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