Genetic and functional analysis reveals TENM4 contributes to schizophrenia.
Genetic and functional analysis reveals TENM4 contributes to schizophrenia.
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遗传和功能分析揭示 TENM4 与精神分裂症有关
DOI：
10.1016/j.isci.2021.103063
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发表时间：
2021-09-24
期刊：
影响因子：
5.8
通讯作者：
Zhou D
中科院分区：
文献类型：
--
作者：
Yi X;Li M;He G;Du H;Li X;Cao D;Wang L;Wu X;Yang F;Chen X;He L;Ping Y;Zhou D
TENM 4是一种神经元可塑性和信号传导相关的基因，是多种精神疾病的共同危险基因。然而，TENM 4在精神分裂症（SCZ）中的作用和机制仍不清楚。我们通过对68个SCZ家族中的TENM 4进行靶向测序，确定了TENM 4基因中可能的致病突变。我们进一步证明了Ten-m的异常表达导致动物模型中学习能力降低、睡眠减少和攻击性增加。RNA测序结果显示Ten-m的异常表达与刺激感知和代谢过程有关，Gene Ontology富集术语为神经发生和ATP酶活性。这项研究提供了强有力的证据，TENM 4有助于SCZ，其功能突变可能是SCZ中观察到的神经回路和行为受损的原因。TENM 4基因中可能的致病性罕见错义突变导致SCZ TEN-m的异常表达导致与SCZ症状相关的行为障碍TEN-m影响刺激、代谢过程、神经发生和ATP酶活性遗传学;人类遗传学;人类遗传学;分子遗传学;神经遗传学;心理学
TENM4, encoding a member of the teneurin protein family, is a risk gene shared by many types of mental diseases and is implicated in neuronal plasticity and signaling. However, the role and the mechanisms of TENM4 in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in the TENM4 gene through target sequencing of TENM4 in 68 SCZ families. We further demonstrated that aberrant expression of Ten-m leads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression of Ten-m was related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence that TENM4 contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ. Possible pathogenic rare missense mutations in TENM4 gene contribute to SCZ Aberrant expression of Ten-m leads to behavioral disturbances related to SCZ symptoms Ten-m affects stimulation, metabolic process, neurogenesis, and ATPase activity Genetics; Human genetics; Human Genetics; Molecular genetics; Neurogenetics; Psychology
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.8
作者：
Hong, Weizhe;Mosca, Timothy J.;Luo, Liqun
通讯作者：
Luo, Liqun
影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
4.8
作者：
Feng, K;Zhou, XH;F채ssler, R
通讯作者：
F채ssler, R
影响因子：
5.4
作者：
Heinrich, Angela;Lourdusamy, Anbarasu;Nees, Frauke
通讯作者：
Nees, Frauke