【原创】大脑基因活动取决于遗传学背景：对药物安全性与有效性的个体差异的可能影响
发布于 2010-10-20 · 浏览 3255 · IP 浙江浙江
这个帖子发布于 14 年零 230 天前，其中的信息可能已发生改变或有所发展。
新的研究发现：虽然是同一基因，如果个体的遗传背景不同，那么该基因在大脑中的活动模式也将有所不同。这一发现可能有助于解释治疗性药物在效力与副作用方面所存在的个体差异，因而对个体化医疗也将有指导意义
——Docofsoul
Gene Activity in the Brain Depends on Genetic Background: Implications for Individual Differences in Drug Safety and Efficacy
ScienceDaily (Oct. 19, 2010) — Researchers at the Allen Institute for Brain Science have found that the same genes have different activity patterns in the brain in individuals with different genetic backgrounds. These findings may help to explain individual differences in the effectiveness and side-effect profiles of therapeutic drugs and thus have implications for personalized medicine.
The study is available in this week's online early edition of the Proceedings of the National Academy of Sciences.
In this study, the authors compared where in the brain each of 49 different pharmaceutically related genes is expressed, or turned on, in seven genetically distinct groups of mice with known genealogical relationships. By analyzing 203 distinct brain areas over 15,000 thin sections of tissue, they precisely mapped where these genes are active, down to the level of individual cells. The genes all encode molecular targets of well-known pharmaceuticals, such as antidepressants, antipsychotics and pain relievers including Prozac, Imitrex, and Aricept.
More than half of the genes examined showed striking, localized differences in expression patterns between the different genetic groups, or strains, of mice. For example, the dopamine D2 receptor gene -- which encodes a target of action of Zyprexa, a drug used for schizophrenia and bipolar disorder -- is active in a memory-related area called the entorhinal cortex in one strain of mice, but not in two others. Because different parts of the brain have different functions, variations in the localization of gene activity likely have functional implications.
"It is clear that to understand how genes translate to behavioral and other differences between individuals and species, we need to look beyond just the inherited sequences of the genes themselves," said Allan Jones, chief executive officer of the Allen Institute for Brain Science. "Our results show that genetic background -- the specific blend of gene variants comprising an individual genome -- can influence how the activity of a given gene is regulated and where it is expressed."
Taken all together, the data from the study demonstrate that closer genetic relatives exhibit fewer differences in gene expression patterns, whereas more distant relatives show greater variation. Interestingly, the researchers found that the expression variations between genetic strains were more likely to be found in areas of the brain that evolved more recently. These regions are most commonly linked to higher order functions such as cognition, social behavior, learning and memory.
"This study shows how large-scale datasets can be used to reveal fundamental biological patterns that would likely be missed otherwise," said Jones. "It is likely that many important differences between individuals and species may result from combinations of many small but clear differences in gene expression."
Jones added, "Our ongoing Allen Human Brain Atlas project, which will provide gene expression data across the brains of multiple donors, will help researchers translate these results from an animal model to a human system."
The data in this study are openly available to the public as the Mouse Diversity Study via the ALLEN Brain Atlas data portal at http://www.brain-map.org or directly at http://mousediversity.alleninstitute.org.
http://www.sciencedaily.com/releases/2010/10/101019132054.htm
========================================================
Gene Activity in the Brain Depends on Genetic Background: Implications for Individual Differences in Drug Safety and Efficacy
大脑基因活动取决于遗传学背景：对药物安全性与有效性的个体差异的可能影响
译者：Docofsoul
ScienceDaily (Oct. 19, 2010) — Researchers at the Allen Institute for Brain Science have found that the same genes have different activity patterns in the brain in individuals with different genetic backgrounds. These findings may help to explain individual differences in the effectiveness and side-effect profiles of therapeutic drugs and thus have implications for personalized medicine.
《每日科学》2010年10月19日报道 —— 艾伦脑科学研究所（the Allen Institute for Brain Science）的研究者发现：不同遗传背景的个体的同一基因其活动模式也有所不同。该发现可能有助于解释治疗性药物存在效力与副作用的个体差异，因而对个体化医疗也将有（指导）意义。
The study is available in this week's online early edition of the Proceedings of the National Academy of Sciences.
这一研究在线发表于美国《国家科学院院刊》（PNAS）本周早版上。
In this study, the authors compared where in the brain each of 49 different pharmaceutically related genes is expressed, or turned on, in seven genetically distinct groups of mice with known genealogical relationships. By analyzing 203 distinct brain areas over 15,000 thin sections of tissue, they precisely mapped where these genes are active, down to the level of individual cells. The genes all encode molecular targets of well-known pharmaceuticals, such as antidepressants, antipsychotics and pain relievers including Prozac, Imitrex, and Aricept.
在这项研究中，作者将系谱关系明确的七组遗传背景各异的小鼠中的49个不同的药理学相关基因的每一个在大脑中的表达或开启位置作了比较。 通过对超过一万五千细薄的组织切片上的203个不同的大脑区域的分析，他们准确地画出了这些基因活动区域地图并（使之）精确到个体细胞水平。所有这些基因都负责熟知的药品（诸如抗抑郁药、精神抑制药与包括百忧解、舒馬曲坦与安理申等在内的止疼片）的分子靶标的编码。
More than half of the genes examined showed striking, localized differences in expression patterns between the different genetic groups, or strains, of mice. For example, the dopamine D2 receptor gene -- which encodes a target of action of Zyprexa, a drug used for schizophrenia and bipolar disorder -- is active in a memory-related area called the entorhinal cortex in one strain of mice, but not in two others. Because different parts of the brain have different functions, variations in the localization of gene activity likely have functional implications.
在小鼠不同的遗传群组或品系之间， 受检查的基因中超过半数的表达模式显示了显著的、本地化的差异。比如说，多巴胺D2受体基因（该基因对再普乐<Zyprexa，用于治疗精神分裂症与躁郁症> 的作用靶标进行编码）在某一小鼠品系的一个称之为内嗅皮质的与记忆有关的区域很活跃，但在其它两个品系（的相关区域）则不然。因为大脑的不同部分有着不同的功能，基因活动定位的变化可能有其功能性的意义。
"It is clear that to understand how genes translate to behavioral and other differences between individuals and species, we need to look beyond just the inherited sequences of the genes themselves," said Allan Jones, chief executive officer of the Allen Institute for Brain Science. "Our results show that genetic background -- the specific blend of gene variants comprising an individual genome -- can influence how the activity of a given gene is regulated and where it is expressed."
艾伦脑科学研究所的首席执行官员Allan Jones 说：“很清楚，要了解基因转化为个体与种类之间的行为与其它差异的具体过程，就必须把眼光放远，不为基因本身的遗传系列所局限。我们的研究结果显示遗传背景，即组成个体基因组的基因变异的特定融合，能够影响一个给定基因活动受调控的具体过程以及该基因的表达位点。”
Taken all together, the data from the study demonstrate that closer genetic relatives exhibit fewer differences in gene expression patterns, whereas more distant relatives show greater variation. Interestingly, the researchers found that the expression variations between genetic strains were more likely to be found in areas of the brain that evolved more recently. These regions are most commonly linked to higher order functions such as cognition, social behavior, learning and memory.
总的来说，来自该研究的数据显示遗传（背景）关联越近，其基因表达模式的差异也就越少；关联越是疏远，差异也就越大。令人感兴趣的是，研究者发现小鼠遗传品系之间的表达的变异更可能在新近进化的大脑区域中被发现。这些区域与诸如认知、社会行为、学习与记忆等次序功能的关联性是最为常见的形式。
"This study shows how large-scale datasets can be used to reveal fundamental biological patterns that would likely be missed otherwise," said Jones. "It is likely that many important differences between individuals and species may result from combinations of many small but clear differences in gene expression."
Jones说：“这个研究显示大型数据集可用于揭示基本的生物模式，而用其它方式则可能与之失之交臂。个体与种类之间的重大差异可能由基因表达的许多细小但清晰的差异的整合的结果。
Jones added, "Our ongoing Allen Human Brain Atlas project, which will provide gene expression data across the brains of multiple donors, will help researchers translate these results from an animal model to a human system."
The data in this study are openly available to the public as the Mouse Diversity Study via the ALLEN Brain Atlas data portal at http://www.brain-map.org or directly at http://mousediversity.alleninstitute.org.
他又补充说：“目前我们正在着手进行的艾伦人类大脑图谱计划，将提供众多捐赠者全脑基因表达数据；这一计划将有助于研究者将这些研究结果从动物模型转化为人类系统模型。” 本研究中的数据以《小鼠多样性研究》（Mouse Diversity Study）通过艾伦大脑图谱数据门户（ALLEN Brain Atlas data portal），对公众开放，网址为： http://www.brain-map.org 或直接点击： http://mousediversity.alleninstitute.org.
（Docofsoul 译于2010-10-20）
——Docofsoul
ScienceDaily (Oct. 19, 2010) — Researchers at the Allen Institute for Brain Science have found that the same genes have different activity patterns in the brain in individuals with different genetic backgrounds. These findings may help to explain individual differences in the effectiveness and side-effect profiles of therapeutic drugs and thus have implications for personalized medicine.
The study is available in this week's online early edition of the Proceedings of the National Academy of Sciences.
In this study, the authors compared where in the brain each of 49 different pharmaceutically related genes is expressed, or turned on, in seven genetically distinct groups of mice with known genealogical relationships. By analyzing 203 distinct brain areas over 15,000 thin sections of tissue, they precisely mapped where these genes are active, down to the level of individual cells. The genes all encode molecular targets of well-known pharmaceuticals, such as antidepressants, antipsychotics and pain relievers including Prozac, Imitrex, and Aricept.
More than half of the genes examined showed striking, localized differences in expression patterns between the different genetic groups, or strains, of mice. For example, the dopamine D2 receptor gene -- which encodes a target of action of Zyprexa, a drug used for schizophrenia and bipolar disorder -- is active in a memory-related area called the entorhinal cortex in one strain of mice, but not in two others. Because different parts of the brain have different functions, variations in the localization of gene activity likely have functional implications.
"It is clear that to understand how genes translate to behavioral and other differences between individuals and species, we need to look beyond just the inherited sequences of the genes themselves," said Allan Jones, chief executive officer of the Allen Institute for Brain Science. "Our results show that genetic background -- the specific blend of gene variants comprising an individual genome -- can influence how the activity of a given gene is regulated and where it is expressed."
Taken all together, the data from the study demonstrate that closer genetic relatives exhibit fewer differences in gene expression patterns, whereas more distant relatives show greater variation. Interestingly, the researchers found that the expression variations between genetic strains were more likely to be found in areas of the brain that evolved more recently. These regions are most commonly linked to higher order functions such as cognition, social behavior, learning and memory.
"This study shows how large-scale datasets can be used to reveal fundamental biological patterns that would likely be missed otherwise," said Jones. "It is likely that many important differences between individuals and species may result from combinations of many small but clear differences in gene expression."
Jones added, "Our ongoing Allen Human Brain Atlas project, which will provide gene expression data across the brains of multiple donors, will help researchers translate these results from an animal model to a human system."
The data in this study are openly available to the public as the Mouse Diversity Study via the ALLEN Brain Atlas data portal at http://www.brain-map.org or directly at http://mousediversity.alleninstitute.org.
http://www.sciencedaily.com/releases/2010/10/101019132054.htm
========================================================
大脑基因活动取决于遗传学背景：对药物安全性与有效性的个体差异的可能影响
译者：Docofsoul
ScienceDaily (Oct. 19, 2010) — Researchers at the Allen Institute for Brain Science have found that the same genes have different activity patterns in the brain in individuals with different genetic backgrounds. These findings may help to explain individual differences in the effectiveness and side-effect profiles of therapeutic drugs and thus have implications for personalized medicine.
《每日科学》2010年10月19日报道 —— 艾伦脑科学研究所（the Allen Institute for Brain Science）的研究者发现：不同遗传背景的个体的同一基因其活动模式也有所不同。该发现可能有助于解释治疗性药物存在效力与副作用的个体差异，因而对个体化医疗也将有（指导）意义。
The study is available in this week's online early edition of the Proceedings of the National Academy of Sciences.
这一研究在线发表于美国《国家科学院院刊》（PNAS）本周早版上。
In this study, the authors compared where in the brain each of 49 different pharmaceutically related genes is expressed, or turned on, in seven genetically distinct groups of mice with known genealogical relationships. By analyzing 203 distinct brain areas over 15,000 thin sections of tissue, they precisely mapped where these genes are active, down to the level of individual cells. The genes all encode molecular targets of well-known pharmaceuticals, such as antidepressants, antipsychotics and pain relievers including Prozac, Imitrex, and Aricept.
在这项研究中，作者将系谱关系明确的七组遗传背景各异的小鼠中的49个不同的药理学相关基因的每一个在大脑中的表达或开启位置作了比较。 通过对超过一万五千细薄的组织切片上的203个不同的大脑区域的分析，他们准确地画出了这些基因活动区域地图并（使之）精确到个体细胞水平。所有这些基因都负责熟知的药品（诸如抗抑郁药、精神抑制药与包括百忧解、舒馬曲坦与安理申等在内的止疼片）的分子靶标的编码。
More than half of the genes examined showed striking, localized differences in expression patterns between the different genetic groups, or strains, of mice. For example, the dopamine D2 receptor gene -- which encodes a target of action of Zyprexa, a drug used for schizophrenia and bipolar disorder -- is active in a memory-related area called the entorhinal cortex in one strain of mice, but not in two others. Because different parts of the brain have different functions, variations in the localization of gene activity likely have functional implications.
在小鼠不同的遗传群组或品系之间， 受检查的基因中超过半数的表达模式显示了显著的、本地化的差异。比如说，多巴胺D2受体基因（该基因对再普乐<Zyprexa，用于治疗精神分裂症与躁郁症> 的作用靶标进行编码）在某一小鼠品系的一个称之为内嗅皮质的与记忆有关的区域很活跃，但在其它两个品系（的相关区域）则不然。因为大脑的不同部分有着不同的功能，基因活动定位的变化可能有其功能性的意义。
"It is clear that to understand how genes translate to behavioral and other differences between individuals and species, we need to look beyond just the inherited sequences of the genes themselves," said Allan Jones, chief executive officer of the Allen Institute for Brain Science. "Our results show that genetic background -- the specific blend of gene variants comprising an individual genome -- can influence how the activity of a given gene is regulated and where it is expressed."
艾伦脑科学研究所的首席执行官员Allan Jones 说：“很清楚，要了解基因转化为个体与种类之间的行为与其它差异的具体过程，就必须把眼光放远，不为基因本身的遗传系列所局限。我们的研究结果显示遗传背景，即组成个体基因组的基因变异的特定融合，能够影响一个给定基因活动受调控的具体过程以及该基因的表达位点。”
Taken all together, the data from the study demonstrate that closer genetic relatives exhibit fewer differences in gene expression patterns, whereas more distant relatives show greater variation. Interestingly, the researchers found that the expression variations between genetic strains were more likely to be found in areas of the brain that evolved more recently. These regions are most commonly linked to higher order functions such as cognition, social behavior, learning and memory.
总的来说，来自该研究的数据显示遗传（背景）关联越近，其基因表达模式的差异也就越少；关联越是疏远，差异也就越大。令人感兴趣的是，研究者发现小鼠遗传品系之间的表达的变异更可能在新近进化的大脑区域中被发现。这些区域与诸如认知、社会行为、学习与记忆等次序功能的关联性是最为常见的形式。
"This study shows how large-scale datasets can be used to reveal fundamental biological patterns that would likely be missed otherwise," said Jones. "It is likely that many important differences between individuals and species may result from combinations of many small but clear differences in gene expression."
Jones说：“这个研究显示大型数据集可用于揭示基本的生物模式，而用其它方式则可能与之失之交臂。个体与种类之间的重大差异可能由基因表达的许多细小但清晰的差异的整合的结果。
Jones added, "Our ongoing Allen Human Brain Atlas project, which will provide gene expression data across the brains of multiple donors, will help researchers translate these results from an animal model to a human system."
The data in this study are openly available to the public as the Mouse Diversity Study via the ALLEN Brain Atlas data portal at http://www.brain-map.org or directly at http://mousediversity.alleninstitute.org.
他又补充说：“目前我们正在着手进行的艾伦人类大脑图谱计划，将提供众多捐赠者全脑基因表达数据；这一计划将有助于研究者将这些研究结果从动物模型转化为人类系统模型。” 本研究中的数据以《小鼠多样性研究》（Mouse Diversity Study）通过艾伦大脑图谱数据门户（ALLEN Brain Atlas data portal），对公众开放，网址为： http://www.brain-map.org 或直接点击： http://mousediversity.alleninstitute.org.
（Docofsoul 译于2010-10-20）
最后编辑于 2010-10-20 · 浏览 3255
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