Heritability of social behavioral phenotypes and preliminary associations with autism spectrum disorder risk genes in rhesus macaques: A whole exome sequencing study.
Heritability of social behavioral phenotypes and preliminary associations with autism spectrum disorder risk genes in rhesus macaques: A whole exome sequencing study.
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DOI：
10.1002/aur.2675
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Rogers J
中科院分区：
文献类型：
--
作者：
Gunter C;Harris RA;Kovacs-Balint Z;Raveendran M;Michopoulos V;Bachevalier J;Raper J;Sanchez MM;Rogers J
非人灵长类动物，特别是猕猴(Macaca Mulatta)是研究神经生物学、发展心理学和神经科学其他方面不可缺少的动物模型。虽然我们在理解对非典型人类社会行为的影响方面取得了显著进展，例如在自闭症谱系障碍(ASD)中观察到的影响，但许多重要的问题仍然存在。提高对非人类灵长类动物特定基因变异和表达的社会行为变异之间的关系的理解，将有助于研究包括ASD在内的行为障碍的危险因素、发育机制和潜在的治疗方法。为了研究遗传对社会行为和互动的关键方面--个人能力和/或社会行为特定方面的动机--的影响，我们使用标准的猕猴人种图和与猕猴相关的人类社会反应性量表修改，量化了幼年恒河猴社交互动中的个体差异。我们的分析表明，青少年社会行为的各个方面表现出显著的遗传遗传性，估计的数量遗传效应类似于人类儿童ASD的描述。我们还进行了外显子组测序，并分析了143个先前被认为影响人类ASD风险的基因的变异。我们发现了特定变异与个体行为和多行为因素得分之间的遗传关联的初步证据。据我们所知，这是第一次证明自由放养的幼年恒河猴的自发社会行为表现出显著的遗传遗传性，然后利用外显子组测序数据来检查与人类ASD相关的基因中潜在的猕猴遗传关联。为了更好地了解导致自闭症谱系障碍的遗传机制和可能的治疗方法，了解非人类灵长类动物之间的遗传差异如何影响大脑功能以及由此导致的社会行为差异将是有价值的。恒河猴表现出许多复杂的社会行为，并能接受各种遗传分析，使它们成为高度相关的动物模型。我们在自然环境中观察了200多只恒河猴，并使用两种不同的方法来识别不同动物在表达各种社会行为方面的差异。然后，我们对动物之间的差异进行了量化分析，发现一些行为受到遗传变异的强烈影响，并可能与特定的DNA序列变异有关，就像在人类身上证明的那样。
Nonhuman primates and especially rhesus macaques (Macaca mulatta) have been indispensable animal models for studies of various aspects of neurobiology, developmental psychology, and other aspects of neuroscience. While remarkable progress has been made in our understanding of influences on atypical human social behavior, such as that observed in autism spectrum disorders (ASD), many significant questions remain. Improved understanding of the relationships among variation in specific genes and variation in expressed social behavior in a nonhuman primate would benefit efforts to investigate risk factors, developmental mechanisms, and potential therapies for behavioral disorders including ASD. To study genetic influences on key aspects of social behavior and interactions—individual competence and/or motivation for specific aspects of social behavior—we quantified individual variation in social interactions among juvenile rhesus macaques using both a standard macaque ethogram and a macaque-relevant modification of the human Social Responsiveness Scale. Our analyses demonstrate that various aspects of juvenile social behavior exhibit significant genetic heritability, with estimated quantitative genetic effects similar to that described for ASD in human children. We also performed exome sequencing and analyzed variants in 143 genes previously suggested to influence risk for human ASD. We find preliminary evidence for genetic association between specific variants and both individual behaviors and multi-behavioral factor scores. To our knowledge, this is the first demonstration that spontaneous social behaviors performed by free-ranging juvenile rhesus macaques display significant genetic heritability and then to use exome sequencing data to examine potential macaque genetic associations in genes associated with human ASD. In order to better understand both the genetic mechanisms that cause and possible therapies for treating autism spectrum disorders, it will be valuable to understand how genetic differences among nonhuman primates can influence brain function and resulting differences in social behavior. Rhesus macaques exhibit many complex social behaviors and are amenable to various kinds of genetic analysis, making them a highly relevant animal model. We watched more than 200 rhesus macaques in a naturalistic environment and used two different measures to identify differences among the animals in their expression of various social behaviors. We then used quantitative analyses of the differences among the animals and found that some behaviors were strongly influenced by genetic variation and may be linked to specific DNA sequence variants, just as has been demonstrated in humans.
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影响因子：
2.7
作者：
Beisner, Brianne;Braun, Nildas;McCowan, Brenda
通讯作者：
McCowan, Brenda
影响因子：
3.9
作者：
Constantino, JN;Davis, SA;Reich, W
通讯作者：
Reich, W
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Constantino JN;Kennon-McGill S;Weichselbaum C;Marrus N;Haider A;Glowinski AL;Gillespie S;Klaiman C;Klin A;Jones W
通讯作者：
Jones W
影响因子：
3.7
作者：
Feczko EJ;Bliss-Moreau E;Walum H;Pruett JR Jr;Parr LA
通讯作者：
Parr LA