Genome Sequencing in Extended Bipolar Pedigrees

扩展双相谱系的基因组测序

基本信息

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
项目类别：
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

项目摘要

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）：该项目将应用整个基因组测序（WGS），以全面地确定有助于严重双相情感障碍（BP-I）的遗传变异，以异常表征良好的扩展谱系。 BP是一种常见的，严重的精神综合征，它是高度可遗传的，但在病因方面是异质的。我们的协作团队已经资助进行广泛的表型（用于BP-I诊断和用于测定BP的生物学基础生物学的定量措施）和基因组广泛的联系和基于26个dedigrees中850个个体密集的SNP基因分型的基因组链接和关联分析。这些谱系均来自哥伦比亚哥斯达黎加中央山谷（CVCR）中部的相关种群分离株，每个人群都有多个受BP-I影响的个体。现在，我们建议对这些家庭的450个人进行深入的WG； WGS数据将用于在整个基因分型个体集合中估算全面的基因组广泛变异。将进行统计和生物信息学分析，以优先考虑在独立研究样本中复制这些变体最有可能有助于BP-I或与BP相关的内型型。该项目的数据将与科学界迅速共享，为旨在更好地理解，治疗和预防精神障碍提供了独特的资源。