An Alternative Splicing Hypothesis For Neuropathology Of Schizophrenia Evidence From Studies On Historical Candidate Genes And Multiomics Data Chuyi Zhang Xiao Xiao Zhuohua Zhang Zhonghua Hu Ming Li by Chu-yi Zhang & Xiao Xiao & Zhuohua Zhang & Zhonghua Hu & Ming Li 101038/S4138002101037W instant download after payment.

Alternative splicing of schizophrenia risk genes, such as DRD2, GRM3, and DISC1, has been extensively described.Nevertheless, the alternative splicing characteristics of the growing number of schizophrenia risk genes identified throughgenetic analyses remain relatively opaque. Recently, transcriptomic analyses in human brains based on short-read RNA1234567890();,:1234567890();,:sequencing have discovered many “local splicing” events (e.g., exon skipping junctions) associated with genetic risk ofschizophrenia, and further molecular characterizations have identified novel spliced isoforms, such as AS3MTd2d3 andZNF804AE3E4. In addition, long-read sequencing analyses of schizophrenia risk genes (e.g., CACNA1C and NRXN1) haverevealed multiple previously unannotated brain-abundant isoforms with therapeutic potentials, and functional analyses ofKCNH2-3.1 and Ube3a1 have provided examples for investigating such spliced isoforms in vitro and in vivo. These findingssuggest that alternative splicing may be an essential molecular mechanism underlying genetic risk of schizophrenia,however, the incomplete annotations of human brain transcriptomes might have limited our understanding of schizophreniapathogenesis, and further efforts to elucidate these transcriptional characteristics are urgently needed to gain insights into theillness-correlated brain physiology and pathology as well as to translate genetic discoveries into novel therapeutic targets.