Association of CDH11 with Autism Spectrum Disorder Revealed by Matched-gene Co-expression Analysis and Mouse Behavioral Studies.
Association of CDH11 with Autism Spectrum Disorder Revealed by Matched-gene Co-expression Analysis and Mouse Behavioral Studies.
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匹配基因共表达分析和小鼠行为研究揭示 CDH11 与自闭症谱系障碍的关联
DOI：
10.1007/s12264-021-00770-0
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发表时间：
2022-01
影响因子：
5.6
通讯作者：
Yuan XB
中科院分区：
文献类型：
--
作者：
Wu N;Wang Y;Jia JY;Pan YH;Yuan XB
已报道了大量自闭症谱系障碍 (ASD) 的推定风险基因。大多数这些易感基因在发育中的大脑中的功能仍然未知，它们的变异与自闭症特征之间的因果关系尚未确定。本研究的目的是基于对一组高置信度 ASD 风险基因 (hcASD) 的基因共表达分析，在全基因组水平上预测假定的风险基因。结果表明，三个基因特征——基因大小、mRNA 丰度和鸟嘌呤胞嘧啶含量——影响 hcASD 的全基因组共表达谱。为了避免基因共表达分析中这些特征的干扰，我们开发了一种方法，通过统计比较该基因与 hcASD 的共表达谱与该基因与特征匹配基因的排列基因集的共表达谱，来确定该基因是否与 hcASD 显着共表达。该方法被称为“匹配基因共表达分析”(MGCA)。通过 MGCA，我们证明了 hcASD 发育表达谱的收敛性，并提高了风险基因预测的效率。对最近报道的两个 ASD 候选基因 CDH11 和 CDH9 的分析结果表明，CDH11 而不是 CDH9 参与 ASD。与这一预测一致的是，行为研究表明，Cdh11 缺失小鼠（而非 Cdh9 缺失小鼠）具有多种类似自闭症的行为改变。这项研究强调了 MGCA 在揭示 ASD 相关基因方面的力量以及 CDH11 在 ASD 中的潜在作用。
A large number of putative risk genes for autism spectrum disorder (ASD) have been reported. The functions of most of these susceptibility genes in developing brains remain unknown, and causal relationships between their variation and autism traits have not been established. The aim of this study was to predict putative risk genes at the whole-genome level based on the analysis of gene co-expression with a group of high-confidence ASD risk genes (hcASDs). The results showed that three gene features – gene size, mRNA abundance, and guanine-cytosine content – affect the genome-wide co-expression profiles of hcASDs. To circumvent the interference of these features in gene co-expression analysis, we developed a method to determine whether a gene is significantly co-expressed with hcASDs by statistically comparing the co-expression profile of this gene with hcASDs to that of this gene with permuted gene sets of feature-matched genes. This method is referred to as "matched-gene co-expression analysis" (MGCA). With MGCA, we demonstrated the convergence in developmental expression profiles of hcASDs and improved the efficacy of risk gene prediction. The results of analysis of two recently-reported ASD candidate genes, CDH11 and CDH9, suggested the involvement of CDH11, but not CDH9, in ASD. Consistent with this prediction, behavioral studies showed that Cdh11-null mice, but not Cdh9-null mice, have multiple autism-like behavioral alterations. This study highlights the power of MGCA in revealing ASD-associated genes and the potential role of CDH11 in ASD.
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影响因子：
6.2
作者：
Cukier HN;Dueker ND;Slifer SH;Lee JM;Whitehead PL;Lalanne E;Leyva N;Konidari I;Gentry RC;Hulme WF;Booven DV;Mayo V;Hofmann NK;Schmidt MA;Martin ER;Haines JL;Cuccaro ML;Gilbert JR;Pericak-Vance MA
通讯作者：
Pericak-Vance MA
影响因子：
30.8
作者：
Doan, Ryan N.;Lim, Elaine T.;Yu, Timothy W.
通讯作者：
Yu, Timothy W.
影响因子：
5.2
作者：
Gadow, KD;Devincent, CJ;Azizian, A
通讯作者：
Azizian, A
影响因子：
14.9
作者：
Basu SN;Kollu R;Banerjee-Basu S
通讯作者：
Banerjee-Basu S
影响因子：
10.6
作者：
Di Martino, Adriana;Kelly, Clare;Grzadzinski, Rebecca;Zuo, Xi-Nian;Mennes, Maarten;Angeles Mairena, Maria;Lord, Catherine;Castellanos, F. Xavier;Milham, Michael P.
通讯作者：
Milham, Michael P.