Genetic Test for Schizophrenia Susceptibility: Targeted

精神分裂症易感性基因检测：有针对性

• 批准号: 7155575
• 负责人: Mark David Brennan
• 金额: $ 24.87万
• 依托单位: SUREGENE, LLC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-26 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155575
• 关键词: African American; alleles; behavioral /social science research tag; behavioral genetics; biotechnology; bipolar depression; caucasian American; clinical research; diagnosis design /evaluation; family genetics; genetic disorder diagnosis; genetic markers; genetic screening; genetic susceptibility; human genetic material tag; human population genetics; human tissue; linkage disequilibriums; mental disorder diagnosis; quantitative trait loci; schizophrenia; twin /multiplet

DESCRIPTION (provided by applicant): The long term objective of this project is to develop validated, genotype-based biomarkers to aid in more accurate diagnosis of schizophrenia and related schizophrenia spectrum disorders, including bipolar disorder. SureGene, LLC is developing two novel genetic tests, one based on the SULT4A1 gene on chromosome 22q (which is supported by a multipoint LOD score of 4.78, assuming genetic heterogeneity in NIMH family samples) and another involving proprietary genetic markers in conjunction with novel microdeletions elsewhere in the genome (odds ratio of approximately 15). These tests need to be further refined before they are ready for general clinical and research use. Additionally, SureGene plans to determine if chromosomal linkages called quantitative trait loci (QTL) that significantly affect behavioral variation in the human population can be used to define novel genes influencing diagnostic components of schizophrenia spectrum disorders. First, to test the hypothesis that chromosomal regions contributing to schizophrenia-related phenotypes in an unselected population contain one or more genes influencing susceptibility to spectrum disorders we will perform targeted microsatellite and single nucleotide polymorphism genotyping with NIMH schizophrenia and bipolar family samples and evaluate the results by linkage analyses and transmission disequilibrium testing. Second, we will determine the frequencies of putative susceptibility haplotypes for novel loci in populations of schizophrenia subjects, and control African American and European American populations, in order to get a more complete picture of the relative risks, or odds ratios, associated with these genetic tests. Finally we will analyze the molecular nature of a targeted set of putative susceptibility alleles. Using quantitative polymerase chain reaction methods, we will find the end points of the novel deletions and describe the region of overlap. Also, we will perform targeted resequencing of novel positional candidate genes with the goal of better understanding the molecular mechanisms contributing to increased risk. We anticipate that intellectual property (IP) will come out of the proposed research in the form of genotype-based diagnostic products and services. Such products should be helpful to individuals suffering from schizophrenia and related disorders, their families and health care providers, and researchers seeking to improve diagnosis and treatment.

描述（由申请人提供）：该项目的长期目标是开发经过验证的基于基因型的生物标志物，以帮助更准确地诊断精神分裂症和相关的精神分裂症谱系障碍，包括双相情感障碍。 Suregene，LLC正在开发两个新型的遗传测试，一个基于染色体22q上的Sult4a1基因（由NIMH家族样本中的遗传异质性的多点LOD得分支持4.78），而在其他涉及与小微生物中的新型基因组相结合的遗传标记的遗传异质性（在NIMH家族样本中具有遗传异质性）。这些测试需要进一步完善，然后才能准备好进行一般的临床和研究用途。此外，Suregene计划确定显着影响人口行为差异的染色体连接是否称为定量性状基因座（QTL），可用于定义影响精神分裂症谱系疾病的诊断成分的新型基因。首先，为了检验以下假设：在未选择的人群中有助于精神分裂症相关的表型的染色体区域包含一个或多个影响谱系障碍易感性的基因，我们将执行靶向的微卫星和单核苷酸的靶向微卫星和单型型型基因分型，并通过NIMH Schizopollenia和Bip olthreniables进行分析，并通过链接结果分析结果，并将其链接得法分析。测试。其次，我们将确定精神分裂症受试者人群中新型基因座的假定易感性单倍型的频率，以及控制非裔美国人和欧美人群，以便更完整地了解与这些基因检验相关的相对风险或优势比。最后，我们将分析一组靶向推定易感性等位基因的分子性质。使用定量聚合酶链反应方法，我们将找到新的缺失的终点并描述重叠区域。此外，我们将对新型位置候选基因进行有针对性的重新方程，以更好地了解有助于增加风险的分子机制。我们预计，知识产权（IP）将以基于基因型的诊断产品和服务的形式来自拟议的研究。此类产品应有助于患有精神分裂症和相关疾病，其家人和医疗保健提供者以及寻求改善诊断和治疗的研究人员。