Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity.
Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity.
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DOI：
10.1371/journal.pone.0130900
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lawrie SM
中科院分区：
文献类型：
--
作者：
Whalley HC;Dimitrova R;Sprooten E;Dauvermann MR;Romaniuk L;Duff B;Watson AR;Moorhead B;Bastin M;Semple SI;Giles S;Hall J;Thomson P;Roberts N;Hughes ZA;Brandon NJ;Dunlop J;Whitcher B;Blackwood DH;McIntosh AM;Lawrie SM
携带罕见的、但具有生物学信息的基因变异的个体提供了一个独特的机会来模拟重大精神疾病并了解疾病机制。这种变异的罕见意味着他们的研究只涉及较小的群体数量，但它们是已知的导致重大精神疾病的最强烈的遗传风险因素之一，可能会对神经产生重大影响。DISC1(在精神分裂症1中中断)是一种包含一个这样的风险变量的基因，通过1和11号染色体的平衡易位；t(1；11)(q42.1；q14.3)，在一个苏格兰家庭中被鉴定出来。在最初的家系中，我们检查了t(1；11)易位对白质完整性的影响，用分数各向异性(FA)来衡量。这包括有易位的家庭成员(n=7)和没有易位的家庭成员(n=13)，以及精神病患者的临床对照样本(n=34)，以及一组健康对照(n=33)。我们报告有5个脑团的白质完整性降低，包括膝盖骨、右下额枕束、声辐射和穹隆。对混合性精神病患者的分析也显示上述区域的白质完整性降低。痂体内的FA值与阳性精神病症状严重程度显著相关。我们证明t(1；11)易位与额连合和联合纤维束中白质完整性降低有关。这些发现与在受影响的精神病患者和DISC1动物模型中显示的结果重叠，并突显了罕见但具有生物学信息的突变在模拟精神病中的价值。
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). 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). 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. 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.
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影响因子：
3.5
作者：
Eastwood, Sharon L.;Walker, Mary;Harrison, Paul J.
通讯作者：
Harrison, Paul J.
影响因子：
10.6
作者：
El-Hassar, Lynda;Simen, Arthur A.;Duque, Alvaro;Patel, Kiran D.;Kaczmarek, Leonard K.;Arnsten, Amy F. T.;Yeckel, Mark F.
通讯作者：
Yeckel, Mark F.
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作者：
Cannon, TD;Hennah, W;Peltonen, L
通讯作者：
Peltonen, L
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9.8
作者：
Blackwood, DHR;Fordyce, A;Muir, WJ
通讯作者：
Muir, WJ
影响因子：
4.5
作者：
Ellison-Wright, Ian;Bullmore, Edward T.
通讯作者：
Bullmore, Edward T.