The biological role of the cadherin gene FAT in bipolar disorder susceptibility

钙粘蛋白基因 FAT 在双相情感障碍易感性中的生物学作用

• 批准号: nhmrc : 376011
• 负责人: A/Pr Ian Blair
• 金额: $ 33.97万
• 依托单位: The University of New South Wales
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/biological-role-cadherin-disorder-susceptibility/76048
• 关键词: biological; role; cadherin; gene; FAT

Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1%. The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide fifteen-fold. There is a pressing need to define more clearly the biological basis of bipolar disorder as a necessary prerequisite to improved diagnosis and treatment. The underlying causes of bipolar disorder remain unknown. However, family studies reveal the high heritability of bipolar disorder and this familial clustering provides an opportunity to use genetic approaches to identify the predisposing genes. The long-term aim of our research is to investigate the biology of those genes that either cause or predispose to bipolar disorder. We have previously used genetic approaches to identify the first bipolar disorder susceptibility gene, a cell contact molecule located on chromosome 4 that is from the cadherin family. The aim of this proposal is to understand how this gene contributes to the risk of developing bipolar disorder. This will be achieved by identifying how the cadherin susceptibility gene, termed 'FAT' results in altered properties in laboratory assays or in altered behaviours in animal models. Identifying the genes responsible for bipolar disorder and understanding their contribution to the biological basis of this severe psychiatric condition is essential to translate these discoveries into improvements in the ability to diagnose, treat and prevent the illness.

双相情感障碍（躁狂抑郁症）是一种严重的情绪障碍，终生患病率高达1%。这种疾病的特点是异常的情绪波动，导致躁狂和抑郁的时期，并在发作之间恢复正常行为。这种情况对患者有严重的影响，被证明是世界卫生组织全球疾病负担报告中第六大致残性疾病，并使自杀风险增加15倍。迫切需要更明确地定义双相情感障碍的生物学基础，作为改善诊断和治疗的必要先决条件。双相情感障碍的根本原因仍然未知。然而，家族研究揭示了双相情感障碍的高遗传性，这种家族聚集性提供了一个机会，使用遗传学方法来确定易感基因。我们研究的长期目标是调查那些导致或易患双相情感障碍的基因的生物学。我们以前使用遗传学方法来确定第一个双相情感障碍易感基因，位于4号染色体上的细胞接触分子，来自钙粘蛋白家族。这项提案的目的是了解这种基因如何导致双相情感障碍的风险。这将通过确定钙粘蛋白易感基因（称为“FAT”）如何在实验室测定中改变性质或在动物模型中改变行为来实现。确定负责双相情感障碍的基因，并了解它们对这种严重精神疾病的生物学基础的贡献，对于将这些发现转化为诊断，治疗和预防疾病的能力的改善至关重要。