Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity

Autor: Barbara Duff, Andrew M. McIntosh, Nicholas J. Brandon, Neil Roberts, Stephen Giles, Emma Sprooten, Bill Moorhead, Zoë A. Hughes, Jeremy Hall, Pippa A. Thomson, Liana Romaniuk, Scott Semple, Rali Dimitrova, Maria R. Dauvermann, Andrew Watson, Heather C. Whalley, Stephen M. Lawrie, Mark E. Bastin, Brandon Whitcher, John Dunlop, Douglas Blackwood
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Male
Bipolar Disorder
Genu of the corpus callosum
Schizophrenia/genetics
White Matter/pathology
lcsh:Medicine
translocation
Chromosomal translocation
Corpus callosum
Chromosomes
Human
Pair 11/genetics
Severity of Illness Index
Translocation
Genetic
Corpus Callosum
corpus callosum
Exons/genetics
Nerve Tissue Proteins/deficiency
lcsh:Science
Genetics
Multidisciplinary
biology
Bipolar Disorder/genetics
White matter
Exons
Middle Aged
Cyclothymic Disorder/genetics
White Matter
Cyclothymic Disorder
medicine.anatomical_structure
Diffusion Tensor Imaging
Chromosomes
Human
Pair 1/genetics
Chromosomes
Human
Pair 1
Female
Depressive Disorder
Major/genetics
Research Article
Adult
medicine.medical_specialty
Psychosis
Adolescent
Nerve Tissue Proteins
Young Adult
DISC1
Fractional anisotropy
medicine
Humans
Bipolar disorder
Psychiatry
Depressive Disorder
Major
Chromosomes
Human
Pair 11
lcsh:R
medicine.disease
R1
schizophrenia
Schizophrenia
biology.protein
lcsh:Q
Corpus Callosum/pathology
Zdroj: Whalley, H C, Dimitrova, R, Sprooten, E, Dauvermann, MR, Romaniuk, L, Duff, B, Watson, A, Moorhead, B, Bastin, M E, Semple, S, Giles, S, Hall, J, Thomson, P, Roberts, N, Hughes, Z, Brandon, N, Dunlop, J, Whitcher, B, Blackwood, D, McIntosh, A M & Lawrie, S M 2015, ' Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity ', PLoS ONE, vol. 10, no. 6, e0130900 . https://doi.org/10.1371/journal.pone.0130900
PLoS ONE
Whalley, H, Dimitrova, R, Sprooten, E, Dauvermann, M R, Romaniuk, L, Duff, B, Watson, A, Moorhead, B, Bastin, M, Semple, S I, Giles, S, Hall, J, Thomson, P, Roberts, N, Hughes, Z, J Brandon, N, Dunlop, J, Whitcher, B, Blackwood, D, McIntosh, A & Lawrie, S 2015, ' Effects of a balanced translocation between chromosomes 1 and 11 disrupting the DISC1 locus on white matter integrity ', PLoS ONE . https://doi.org/10.1371/journal.pone.0130900
PLoS ONE, Vol 10, Iss 6, p e0130900 (2015)
ISSN: 1932-6203
Popis: Objective\ud \ud Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3).\ud Method\ud \ud Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33).\ud Results\ud \ud We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity.\ud Conclusions\ud \ud We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis.
Databáze: OpenAIRE
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