MicroRNA and MicroRNA-Target Variants Associated with Autism Spectrum Disorder and Related Disorders.
MicroRNA and MicroRNA-Target Variants Associated with Autism Spectrum Disorder and Related Disorders.
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作者：
自闭症谱系障碍（ASD）是一种具有复杂和异质性遗传病因的儿童神经发育障碍。MicroRNA（miRNA）是一类小分子非编码RNA，可在转录后调控ASD风险基因，影响ASD及其相关疾病的广泛分子通路。使用全基因组测序，我们分析了新泽西语言和自闭症遗传学研究（NJLAGS）队列中73个家庭的272个样本。招募至少有一名ASD患者的家庭，并进一步评估语言障碍，阅读障碍和其他相关表型。在数据集中共鉴定了5104个miRNA变体和1，181，148个3′非翻译区（3′ UTR）变体。在应用多个过滤标准（包括群体等位基因频率、大脑表达、miRNA功能区域和遗传模式）后，我们在5种大脑表达的miRNA（靶向326个基因）和152个基因的3 'UTR miRNA靶向区域中鉴定了高置信度变体。SCP 2、UCGC等基因在多个家系中被发现。使用基因本体过度表达分析和蛋白质-蛋白质相互作用网络分析，我们确定了对神经发育重要的基因和通路的集群。本研究中发现的miRNA和miRNA靶基因可能与神经发育障碍有关，应考虑进行进一步的功能研究。
Autism spectrum disorder (ASD) is a childhood neurodevelopmental disorder with a complex and heterogeneous genetic etiology. MicroRNA (miRNA), a class of small non-coding RNAs, could regulate ASD risk genes post-transcriptionally and affect broad molecular pathways related to ASD and associated disorders. Using whole-genome sequencing, we analyzed 272 samples in 73 families in the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Families with at least one ASD patient were recruited and were further assessed for language impairment, reading impairment, and other associated phenotypes. A total of 5104 miRNA variants and 1,181,148 3′ untranslated region (3′ UTR) variants were identified in the dataset. After applying several filtering criteria, including population allele frequency, brain expression, miRNA functional regions, and inheritance patterns, we identified high-confidence variants in five brain-expressed miRNAs (targeting 326 genes) and 3′ UTR miRNA target regions of 152 genes. Some genes, such as SCP2 and UCGC, were identified in multiple families. Using Gene Ontology overrepresentation analysis and protein–protein interaction network analysis, we identified clusters of genes and pathways that are important for neurodevelopment. The miRNAs and miRNA target genes identified in this study are potentially involved in neurodevelopmental disorders and should be considered for further functional studies.
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影响因子：
3.3
作者：
Erbeli F;Rice M;Paracchini S
通讯作者：
Paracchini S
影响因子：
4.9
作者：
Hare-Harris, Abby E.;Mitchel, Marissa W.;Brzustowicz, Linda M.
通讯作者：
Brzustowicz, Linda M.
DOI：
10.1176/appi.ajp.2013.12081103
发表时间：
2014-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Bartlett CW;Hou L;Flax JF;Hare A;Cheong SY;Fermano Z;Zimmerman-Bier B;Cartwright C;Azaro MA;Buyske S;Brzustowicz LM
通讯作者：
Brzustowicz LM
影响因子：
4.6
作者：
Griesi-Oliveira K;Suzuki AM;Alves AY;Mafra ACCN;Yamamoto GL;Ezquina S;Magalhães YT;Forti FL;Sertie AL;Zachi EC;Vadasz E;Passos-Bueno MR
通讯作者：
Passos-Bueno MR
影响因子：
5.1
作者：
Gu, Xi;Li, Aili;Wang, Xuemin
通讯作者：
Wang, Xuemin