Genome Sequencing in Extended Bipolar Pedigrees

扩展双相谱系的基因组测序

• 批准号: 8474847
• 负责人: NELSON B. FREIMER
• 金额: $ 67.24万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8474847
• 关键词: Abbreviations; Accounting; Affect; Bioinformatics; Biological; Biological Assay; Biology; Bipolar Disorder; Cataloging; Catalogs; Cell Line; Chromosome Mapping; Code; Collection; Colombia; Communities; Costa Rica; Data; Diagnosis; Disease; Family; Functional RNA; Funding; Future; Genes; Genetic; Genetic Variation; Genome; Genotype; Goals; Heritable Quantitative Trait; Individual; Informatics; Investigation; Investments; Maps; Measures; Mental disorders; Mutation; Nucleotides; Phenotype; Population; Predisposition; Prevention; Psychiatric Diagnosis; Quantitative Trait Loci; Resources; Rest; Risk; SNP genotyping; Sampling; Sampling Studies; Site; Syndrome; Variant; base; cost; endophenotype; exome sequencing; follow-up; genetic linkage analysis; genetic pedigree; genetic variant; genome sequencing; genome wide association study; genome-wide; genome-wide linkage; lymphoblast; member; mental disorder prevention; neurogenetics; psychogenetics; trait

DESCRIPTION (provided by applicant): This project will apply whole genome sequencing (WGS) to comprehensively identify the genetic variants contributing to the risk of severe bipolar disorder (BP-I) in an exceptionally well characterized set of extended pedigrees. BP is a common, severe psychiatric syndrome, which is highly heritable yet etiologically heterogeneous. Our collaborative team is already funded to conduct extensive phenotyping (for both the BP-I diagnosis and for quantitative measures that assay the biology underlying BP, i.e. endophenotypes) and genome wide linkage and association analyses based on dense SNP genotyping in 850 individuals in 26 pedigrees. These pedigrees, each with multiple BP-I affected individuals, are drawn from the related population isolates of the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (ANT). We now propose to conduct deep WGS in 450 individuals from these families; the WGS data will be used to impute comprehensive genome wide variation in the entire set of genotyped individuals. Statistical and bioinformatic analyses will be undertaken to prioritize for replication in independent study samples the variants most likely to be contributing to BP-I or BP-related endophenotypes. The data from this project will be shared rapidly with the scientific community, providing a unique resource for efforts aimed at a better understanding, treatment, and prevention of mental disorders.

描述（由申请人提供）：该项目将应用全基因组测序（WGS）来全面识别导致严重双相情感障碍（BP-I）风险的遗传变异，这是一组非常有特征的扩展谱系。BP是一种常见的、严重的精神综合征，具有高度遗传性，但在病因上具有异质性。我们的合作团队已经获得了资金，可以进行广泛的表型分析（用于BP- i诊断和定量测量BP生物学基础，即内部表型），以及基于26个家系850个个体的密集SNP基因分型的全基因组连锁和关联分析。这些谱系，每个谱系都有多个bp - 1感染个体，来自哥斯达黎加中央山谷（CVCR）和哥伦比亚安蒂奥基亚（ANT）的相关种群分离株。我们现在建议对来自这些家庭的450个人进行深度WGS；WGS数据将用于估算整个基因型个体的全面基因组变异。将进行统计和生物信息学分析，以便在独立研究样本中优先考虑最可能导致bp - 1或bp相关内表型的变异。该项目的数据将迅速与科学界共享，为旨在更好地理解、治疗和预防精神障碍的努力提供独特的资源。