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dc.contributor.authorLang, B.
dc.contributor.authorPu, J.
dc.contributor.authorHunter, I.
dc.contributor.authorLiu, M.
dc.contributor.authorMartin-Granados, C.
dc.contributor.authorReilly, T. J.
dc.contributor.authorGao, G.-D.
dc.contributor.authorGuan, Z.-L.
dc.contributor.authorLi, W.-D.
dc.contributor.authorShi, Y.-Y.
dc.contributor.authorHe, G.
dc.contributor.authorHe, L.
dc.contributor.authorStefansson, H.
dc.contributor.authorSt Clair, D.
dc.contributor.authorBlackwood, D. H.
dc.contributor.authorMcCaig, C. D.
dc.contributor.authorShen, S.
dc.identifier.citationLang, B. Pu, J.; Hunter, I.; Liu, M.; Martin-Granados, C.; Reilly, T. J.; Gao, G.-D.; Guan, Z.-L.; Li, W.-D.; Shi, Y.-Y.; He, G.; He, L.; Stefansson, H.; St Clair, D.; Blackwood, D. H.; McCaig, C. D.; Shen, S. (2013). Recurrent deletions of ulk4 in schizophrenia: a gene crucial for neuritogenesis and neuronal motility. Journal of Cell Science 127 (3), 630-640
dc.description.abstractAlthough many pathogenic copy number variations (CNVs) are associated with neuropsychiatric diseases, few of them have been functionally characterised. Here we report multiple schizophrenia cases with CNV abnormalities specific to unc-51-like kinase 4 (ULK4), a serine/threonine kinase gene. Deletions spanning exons 21-34 of ULK4 were present in 4 out of 3391 schizophrenia patients from the International Schizophrenia Consortium, but absent in 3181 controls. Deletions removing exons 33 and 34 of the large splice variant of ULK4 also were enriched in Icelandic schizophrenia and bipolar patients compared with 98,022 controls (P=0.0007 for schizophrenia plus bipolar disorder). Combining the two cohorts gives a P-value less than 0.0001 for schizophrenia, or for schizophrenia plus bipolar disorder. The expression of ULK4 is neuron-specific and developmentally regulated. ULK4 modulates multiple signalling pathways that include ERK, p38, PKC and JNK, which are involved in stress responses and implicated in schizophrenia. Knockdown of ULK4 disrupts the composition of microtubules and compromises neuritogenesis and cell motility. Targeted Ulk4 deletion causes corpus callosum agenesis in mice. Our findings indicate that ULK4 is a rare susceptibility gene for schizophrenia.
dc.publisherThe Company of Biologists
dc.relation.ispartofJournal of Cell Science
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.subjectneurite branching
dc.subjectserine/threonine kinase
dc.subjectgenome-wide association
dc.subjectn-terminal kinase
dc.subjectpluripotent stem-cells
dc.subjectserine/threonine kinase
dc.subjectmatter abnormalities
dc.subjectprefrontal cortex
dc.subjectpyramidal neurons
dc.subjectneurite growth
dc.titleRecurrent deletions of ulk4 in schizophrenia: a gene crucial for neuritogenesis and neuronal motility

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