A promising therapeutic strategy to promote the regeneration of injured axons in the adult central nervous system（CNS）is the transplantation of cells or tissues that can modify the local host environment and support...A promising therapeutic strategy to promote the regeneration of injured axons in the adult central nervous system（CNS）is the transplantation of cells or tissues that can modify the local host environment and support the growth of regenerating axons.展开更多
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 ...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.展开更多
基金We thank Drs Chenbing Guan and Kui Cui （Institute of Neuroscience, Shanghai Institute for Biological Science, China） for technical support in setting up the single-cell migration assay, and Dr Qian Hu （Institute of Neuroscience, Shanghai Institute for Biological Science, China） for microscopic imaging. This study was supported by the National Key Basic Research Program （2006CB500702）, Ministry of Science and Technology of China （2007CB947100）, National Natural Science Foundation of China （30530240 and 30770657）, Program for Changdiang Scholars and Innovative Research Teams in Universities （IRT0528）, and Shanghai Metropolitan Fund for Research and Development （07DJ14005）.
基金supported by NIH NS055976Craig H.Neilsen Foundation 280850
文摘A promising therapeutic strategy to promote the regeneration of injured axons in the adult central nervous system（CNS）is the transplantation of cells or tissues that can modify the local host environment and support the growth of regenerating axons.
基金This work was supported by the National Natural Science Foundation of China(31871501 and ISF-32061143016)the Hussman Foundation(HIAS15006)the Simons Foundation(296143).
文摘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.
