Research Topics
Genomes and Genes
| J Kirsty MillarSummaryAffiliation: University of Edinburgh Country: UK Publications
| Collaborators
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Detail Information
Publications
Disrupted in schizophrenia 1 (DISC1): subcellular targeting and induction of ring mitochondriaJ Kirsty Millar
Medical Genetics Section, Department of Medical Sciences, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
Mol Cell Neurosci 30:477-84. 2005..DISC1 over-expression produces striking mitochondrial reorganization in some cells, with formation of mitochondrial ring-like structures, indicating a potential involvement of DISC1 in mitochondrial fusion and/or fission...- DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signalingJ Kirsty Millar
Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh EH4 2XU, UK
Science 310:1187-91. 2005..We propose a mechanistic model whereby DISC1 sequesters PDE4B in resting cells and releases it in an activated state in response to elevated cAMP... 
Disrupted in schizophrenia 1 and phosphodiesterase 4B: towards an understanding of psychiatric illnessJ Kirsty Millar
University of Edinburgh, Medical Genetics Section, Molecular Medicine Centre, Crewe Road, Edinburgh EH4 2XU, Scotland, UK
J Physiol 584:401-5. 2007..Dysregulated cAMP signalling in specific cellular compartments may therefore be a predisposing factor for major mental illness...- Disruption of two novel genes by a translocation co-segregating with schizophreniaJ K Millar
Medical Genetics Section, Department of Medical Sciences, The University of Edinburgh, Molecular Medicine Centre and MRC Human Genetics Unit, both at Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
Hum Mol Genet 9:1415-23. 2000..Altogether, these observations indicate that DISC1 and DISC2 should be considered formal candidate genes for susceptibility to psychiatric illness... - Chromosomal location and genomic structure of the human translin-associated factor X gene (TRAX; TSNAX) revealed by intergenic splicing to DISC1, a gene disrupted by a translocation segregating with schizophreniaJ K Millar
Department of Medical Sciences, The University of Edinburgh, Scotland, United Kingdom
Genomics 67:69-77. 2000..1. The TRAX gene consists of six exons with a putative CpG island at the 5' end. Four major transcripts are produced from this gene, of which the smallest, at 2.7 kb, had previously been identified... - DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying psychiatric illnessJ Kirsty Millar
Medical Genetics Section, Department of Medical Sciences, The University of Edinburgh, Edinburgh, UK
Ann Med 36:367-78. 2004..Overall, it is clear from the combination of genetic and functional data that DISC1 and/or DISC2 are emerging as important factors in the molecular genetics of psychiatric illness... - Yeast two-hybrid screens implicate DISC1 in brain development and functionJ Kirsty Millar
Medical Genetics Section, Department of Medical Sciences, The University of Edinburgh, Western General Hospital, Crewe Road, EH4 2XU, Edinburgh, UK
Biochem Biophys Res Commun 311:1019-25. 2003..Intriguingly, mutations in one of the proteins identified, WKL1, have been previously suggested to underlie the aetiology of catatonic schizophrenia... 
PKA phosphorylation of NDE1 is DISC1/PDE4 dependent and modulates its interaction with LIS1 and NDEL1Nicholas J Bradshaw
Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
J Neurosci 31:9043-54. 2011..Mutation of the NDE1 T131 site to mimic PKA phosphorylation inhibits neurite outgrowth. Thus PKA-dependent phosphorylation of the NDE1/LIS1/NDEL1 complex is DISC1-PDE4 modulated and likely to regulate its neural functions...- DISC1 variants 37W and 607F disrupt its nuclear targeting and regulatory role in ATF4-mediated transcriptionElise L V Malavasi
The Centre for Molecular Medicine at the Medical Research Council Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK
Hum Mol Genet 21:2779-92. 2012.... - DISC1, PDE4B, and NDE1 at the centrosome and synapseNicholas J Bradshaw
Medical Genetics Section, Molecular Medicine Centre, Crewe Road, Edinburgh EH4 2XU, United Kingdom
Biochem Biophys Res Commun 377:1091-6. 2008..We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4... - Identification of polymorphisms within Disrupted in Schizophrenia 1 and Disrupted in Schizophrenia 2, and an investigation of their association with schizophrenia and bipolar affective disorderR S Devon
Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, UK
Psychiatr Genet 11:71-8. 2001.... - NDE1 and NDEL1: multimerisation, alternate splicing and DISC1 interactionNicholas J Bradshaw
The Centre for Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh EH4 2XU, UK
Neurosci Lett 449:228-33. 2009..We also show that NDE1 can complex with NDEL1. Together these results predict a high degree of complexity of DISC1-mediated regulation of neuronal activity... - Role of DISC1 in neural development and schizophreniaShaun Mackie
Medical Genetics Section, University of Edinburgh Centre for Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
Curr Opin Neurobiol 17:95-102. 2007..Genetic variants of DISC1 also predispose to related affective (mood) disorders. As a consequence, we can speculate on the mechanisms of DISC1 action and possible routes to treatment for these common, debilitating brain disorders... - DISC1 at 10: connecting psychiatric genetics and neuroscienceDavid J Porteous
Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Trends Mol Med 17:699-706. 2011.... - Disrupted in schizophrenia 1: building brains and memoriesDavid J Porteous
Medical Genetics Section, Edinburgh University Centre for Molecular Medicine, Western General Hospital Campus, Crewe Road, Edinburgh EH4 2XU, UK
Trends Mol Med 12:255-61. 2006..In the long term, this might lead to the discovery of drugs that are more efficacious and safer than currently available ones... - A long-range restriction map across 3 Mb of the chromosome 11 breakpoint region of a translocation linked to schizophrenia: localization of the breakpoint and the search for neighbouring genesJ K Millar
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
Psychiatr Genet 8:175-81. 1998..Novel transcribed sequences of unknown function clustered around putative CpG islands, located approximately 500 kb and 700 kb above the breakpoint, represent the only evidence to date for expressed genes within the mapped region... - Evolutionary constraints on the Disrupted in Schizophrenia locusMartin S Taylor
Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK
Genomics 81:67-77. 2003..The amino acid sequence of DISC1 is diverging rapidly, although a putative nuclear localization signal and discrete blocks of coiled coil are specifically conserved features... - The genetics and biology of DISC1--an emerging role in psychosis and cognitionDavid J Porteous
Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Crewe Road South, Edinburgh
Biol Psychiatry 60:123-31. 2006..Both are potential "drug" targets. DISC1 has thus emerged as a key molecular player in the etiology of major mental illness and in normal brain processes... - A genome scan and follow-up study identify a bipolar disorder susceptibility locus on chromosome 1q42S MacGregor
Institute of Cell, Animal and Population Biology, University of Edinburgh, Kings Buildings, Edinburgh, UK
Mol Psychiatry 9:1083-90. 2004..These results, together with results from a number of other recent studies, stress the importance of the 1q42 region in susceptibility to both BPAD and SCZ... - A t(1;11) translocation linked to schizophrenia and affective disorders gives rise to aberrant chimeric DISC1 transcripts that encode structurally altered, deleterious mitochondrial proteinsJennifer E Eykelenboom
Medical Genetics Section, University of Edinburgh Centre for Molecular Medicine, Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK
Hum Mol Genet 21:3374-86. 2012.... - An allelic association study of two polymorphic markers in close proximity to a balanced translocation t(1:11) that co-segregates with mental illnessJ C Wilson-Annan
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
Psychiatr Genet 7:171-4. 1997.... - Isolation and characterization of the mouse translin-associated protein X (Trax) geneR S Devon
MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
Mamm Genome 11:395-8. 2000 - Genomic structure and localisation within a linkage hotspot of Disrupted In Schizophrenia 1, a gene disrupted by a translocation segregating with schizophreniaJ K Millar
Medical Genetics Section The University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland
Mol Psychiatry 6:173-8. 2001..Information regarding the structure of the DISC1 gene will facilitate assessment of its involvement in the aetiology of major mental illness in psychotic individuals unrelated to carriers of the translocation... - Disrupted in Schizophrenia 1 (DISC1) is a multicompartmentalized protein that predominantly localizes to mitochondriaR James
Medical Genetics Section, Department of Medical Sciences, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, UK
Mol Cell Neurosci 26:112-22. 2004.... - Genetics of schizophrenia and bipolar affective disorder: strategies to identify candidate genesD J Porteous
Medical Genetics Section, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, EH4 2XU
Cold Spring Harb Symp Quant Biol 68:383-94. 2003 - Cytogenetics and gene discovery in psychiatric disordersB S Pickard
Medical Genetics, School of Molecular and Clinical Medicine, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK
Pharmacogenomics J 5:81-8. 2005..Cytogenetic events may provide important insights into neurochemical pathways and cellular processes critical for the development of complex psychiatric phenotypes in the population at large... - Association between the TRAX/DISC locus and both bipolar disorder and schizophrenia in the Scottish populationP A Thomson
Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK
Mol Psychiatry 10:657-68, 616. 2005..This result provides further supporting evidence for DISC1 as a susceptibility factor for both bipolar disorder and schizophrenia, consistent with the diagnoses in the original Scottish translocation family... - The mitosis and neurodevelopment proteins NDE1 and NDEL1 form dimers, tetramers, and polymers with a folded back structure in solutionDinesh C Soares
Medical Genetics Section, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom
J Biol Chem 287:32381-93. 2012..It sheds light on recently identified mutations in the NDE1 gene that cause truncation of the encoded protein. Additionally, analysis of mixed NDE1-NDEL1 complexes demonstrates that NDE1 and NDEL1 can interact directly... - The DISC locus in psychiatric illnessJ E Chubb
Medical Genetics Section, The Centre for Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh, UK
Mol Psychiatry 13:36-64. 2008..DISC1 is a hub protein in a multidimensional risk pathway for major mental illness, and studies of this pathway are opening up opportunities for a better understanding of causality and possible mechanisms of intervention... - Response to Amar J. Klar: The chromosome 1;11 translocation provides the best evidence supporting genetic etiology for schizophrenia and bipolar affective disordersJ Kirsty Millar
Genetics 163:833-5; author reply 837-8. 2003 - Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levelsHannah Murdoch
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
J Neurosci 27:9513-24. 2007..Thus, genetic variation in DISC1 and PDE4 that influence either isoform expression or docking site functioning may directly affect psychopathology... - Behavioral phenotypes of Disc1 missense mutations in miceSteven J Clapcote
Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
Neuron 54:387-402. 2007..This study demonstrates that Disc1 missense mutations in mice give rise to phenotypes related to depression and schizophrenia, thus supporting the role of DISC1 in major mental illness...