Atypical genomic cortical patterning in autism with poor early language outcome.
Atypical genomic cortical patterning in autism with poor early language outcome.
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DOI：
10.1126/sciadv.abh1663
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发表时间：
2021-09-03
期刊：
影响因子：
13.6
通讯作者：
Courchesne E
中科院分区：
文献类型：
--
作者：
Lombardo MV;Eyler L;Pramparo T;Gazestani VH;Hagler DJ Jr;Chen CH;Dale AM;Seidlitz J;Bethlehem RAI;Bertelsen N;Barnes CC;Lopez L;Campbell K;Lewis NE;Pierce K;Courchesne E
大脑皮层的基因组模式在自闭症早期语言结果亚型中是不同的。皮质区域化是通过沿着前后（A-P）和背腹（D-V）梯度的基因组模式发展的。在这里，我们发现，皮质表面积 (SA) 和厚度 (CT) 的规范 A-P 和 D-V 基因组模式存在于早期语言结果良好的典型发育和自闭症幼儿中，而在早期语言结果较差的自闭症幼儿中则不存在。相反，早期语言结果较差的自闭症幼儿的具体特征是 CT 上的次要且独立的基因组模式效应。参与这些影响的基因可以追溯到妊娠中期的 A-P 和 D-V 基因表达梯度和不同的产前细胞类型（例如祖细胞和兴奋性神经元），对于声音学习和人类特异性进化具有重要的功能，并且在富含高外显率自闭症风险基因的产前共表达网络中很突出。早期语言结果不佳的自闭症可能是由产前发育开始的非典型基因组皮质模式解释的，这可能会对以后的区域功能专门化和回路形成产生不利影响。
Genomic patterning of the cerebral cortex is different in autism early language outcome subtypes. Cortical regionalization develops via genomic patterning along anterior-posterior (A-P) and dorsal-ventral (D-V) gradients. Here, we find that normative A-P and D-V genomic patterning of cortical surface area (SA) and thickness (CT), present in typically developing and autistic toddlers with good early language outcome, is absent in autistic toddlers with poor early language outcome. Autistic toddlers with poor early language outcome are instead specifically characterized by a secondary and independent genomic patterning effect on CT. Genes involved in these effects can be traced back to midgestational A-P and D-V gene expression gradients and different prenatal cell types (e.g., progenitor cells and excitatory neurons), are functionally important for vocal learning and human-specific evolution, and are prominent in prenatal coexpression networks enriched for high-penetrance autism risk genes. Autism with poor early language outcome may be explained by atypical genomic cortical patterning starting in prenatal development, which may detrimentally affect later regional functional specialization and circuit formation.
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影响因子：
16.2
作者：
Cadwell, Cathryn R.;Bhaduri, Aparna;Mostajo-Radji, Mohammed A.;Keefe, Matthew G.;Nowakowski, Tomasz J.
通讯作者：
Nowakowski, Tomasz J.
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.1308091110
发表时间：
2013-10-15
影响因子：
11.1
作者：
Chen, Chi-Hua;Fiecas, Mark;Kremen, William S.
通讯作者：
Kremen, William S.