J Kirsty Millar

Summary

Affiliation: University of Edinburgh
Country: UK

Publications

  1. ncbi request reprint Disrupted in schizophrenia 1 (DISC1): subcellular targeting and induction of ring mitochondria
    J 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
  2. ncbi request reprint DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying psychiatric illness
    J Kirsty Millar
    Medical Genetics Section, Department of Medical Sciences, The University of Edinburgh, Edinburgh, UK
    Ann Med 36:367-78. 2004
  3. pmc Disrupted in schizophrenia 1 and phosphodiesterase 4B: towards an understanding of psychiatric illness
    J Kirsty Millar
    University of Edinburgh, Medical Genetics Section, Molecular Medicine Centre, Crewe Road, Edinburgh EH4 2XU, Scotland, UK
    J Physiol 584:401-5. 2007
  4. ncbi request reprint Yeast two-hybrid screens implicate DISC1 in brain development and function
    J 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
  5. ncbi request reprint DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling
    J Kirsty Millar
    Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Edinburgh EH4 2XU, UK
    Science 310:1187-91. 2005
  6. ncbi request reprint 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 schizophrenia
    J K Millar
    Department of Medical Sciences, The University of Edinburgh, Scotland, United Kingdom
    Genomics 67:69-77. 2000
  7. ncbi request reprint Disruption of two novel genes by a translocation co-segregating with schizophrenia
    J 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
  8. pmc PKA phosphorylation of NDE1 is DISC1/PDE4 dependent and modulates its interaction with LIS1 and NDEL1
    Nicholas 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
  9. pmc A t(1;11) translocation linked to schizophrenia and affective disorders gives rise to aberrant chimeric DISC1 transcripts that encode structurally altered, deleterious mitochondrial proteins
    Jennifer 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
  10. pmc DISC1 variants 37W and 607F disrupt its nuclear targeting and regulatory role in ATF4-mediated transcription
    Elise 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

Detail Information

Publications33

  1. ncbi request reprint Disrupted in schizophrenia 1 (DISC1): subcellular targeting and induction of ring mitochondria
    J 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...
  2. ncbi request reprint DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying psychiatric illness
    J 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...
  3. pmc Disrupted in schizophrenia 1 and phosphodiesterase 4B: towards an understanding of psychiatric illness
    J 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...
  4. ncbi request reprint Yeast two-hybrid screens implicate DISC1 in brain development and function
    J 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...
  5. ncbi request reprint DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling
    J 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...
  6. ncbi request reprint 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 schizophrenia
    J 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...
  7. ncbi request reprint Disruption of two novel genes by a translocation co-segregating with schizophrenia
    J 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...
  8. pmc PKA phosphorylation of NDE1 is DISC1/PDE4 dependent and modulates its interaction with LIS1 and NDEL1
    Nicholas 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...
  9. pmc A t(1;11) translocation linked to schizophrenia and affective disorders gives rise to aberrant chimeric DISC1 transcripts that encode structurally altered, deleterious mitochondrial proteins
    Jennifer 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
    ....
  10. pmc DISC1 variants 37W and 607F disrupt its nuclear targeting and regulatory role in ATF4-mediated transcription
    Elise 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
    ....
  11. doi request reprint DISC1, PDE4B, and NDE1 at the centrosome and synapse
    Nicholas 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...
  12. ncbi request reprint Identification of polymorphisms within Disrupted in Schizophrenia 1 and Disrupted in Schizophrenia 2, and an investigation of their association with schizophrenia and bipolar affective disorder
    R S Devon
    Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, UK
    Psychiatr Genet 11:71-8. 2001
    ....
  13. pmc NDE1 and NDEL1: multimerisation, alternate splicing and DISC1 interaction
    Nicholas 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...
  14. ncbi request reprint Role of DISC1 in neural development and schizophrenia
    Shaun 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...
  15. pmc DISC1 at 10: connecting psychiatric genetics and neuroscience
    David 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
    ....
  16. ncbi request reprint Disrupted in schizophrenia 1: building brains and memories
    David 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...
  17. ncbi request reprint 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 genes
    J 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...
  18. doi request reprint DISC1 complexes with TRAK1 and Miro1 to modulate anterograde axonal mitochondrial trafficking
    Fumiaki Ogawa
    University of Edinburgh Centre for Genomics and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Crewe Road, Edinburgh EH4 2XU, UK and
    Hum Mol Genet 23:906-19. 2014
    ....
  19. ncbi request reprint Evolutionary constraints on the Disrupted in Schizophrenia locus
    Martin 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...
  20. ncbi request reprint The genetics and biology of DISC1--an emerging role in psychosis and cognition
    David 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...
  21. ncbi request reprint A genome scan and follow-up study identify a bipolar disorder susceptibility locus on chromosome 1q42
    S 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...
  22. ncbi request reprint An allelic association study of two polymorphic markers in close proximity to a balanced translocation t(1:11) that co-segregates with mental illness
    J C Wilson-Annan
    MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
    Psychiatr Genet 7:171-4. 1997
    ....
  23. ncbi request reprint Genetics of schizophrenia and bipolar affective disorder: strategies to identify candidate genes
    D 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
  24. ncbi request reprint Cytogenetics and gene discovery in psychiatric disorders
    B 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...
  25. ncbi request reprint Disrupted in Schizophrenia 1 (DISC1) is a multicompartmentalized protein that predominantly localizes to mitochondria
    R 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
    ....
  26. ncbi request reprint Isolation and characterization of the mouse translin-associated protein X (Trax) gene
    R S Devon
    MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
    Mamm Genome 11:395-8. 2000
  27. ncbi request reprint Association between the TRAX/DISC locus and both bipolar disorder and schizophrenia in the Scottish population
    P 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...
  28. ncbi request reprint Genomic structure and localisation within a linkage hotspot of Disrupted In Schizophrenia 1, a gene disrupted by a translocation segregating with schizophrenia
    J 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...
  29. pmc The mitosis and neurodevelopment proteins NDE1 and NDEL1 form dimers, tetramers, and polymers with a folded back structure in solution
    Dinesh 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...
  30. ncbi request reprint The DISC locus in psychiatric illness
    J 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...
  31. pmc Response to Amar J. Klar: The chromosome 1;11 translocation provides the best evidence supporting genetic etiology for schizophrenia and bipolar affective disorders
    J Kirsty Millar
    Genetics 163:833-5; author reply 837-8. 2003
  32. ncbi request reprint Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels
    Hannah 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...
  33. ncbi request reprint Behavioral phenotypes of Disc1 missense mutations in mice
    Steven 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...