中风综合基因组学-猫眼课题宝

中风综合基因组学

批准号：

7772779

负责人：

Rose Du

金额：

$17.9万

依托单位：

BRIGHAM AND WOMEN'S HOSPITAL

依托单位国家：

美国

项目类别：

财政年份：

2009

资助国家：

美国

项目状态：

已结题

起止时间：

2009-09-15 至 2014-08-31

来源：

https://reporter.nih.gov/project-details/7772779

关键词：

Adult Affect Atherosclerosis Bioinformatics Candidate Disease Gene Cause of Death Cerebral Infarction Cerebral Ischemia Cerebrovascular Disorders Cerebrum Cessation of life Classification Code Comparative Genomic Analysis Complex Computer Simulation DNA Databases Dementia Disease Ensure Environment Environmental Risk Factor Feasibility Studies Gene Expression Gene Expression Microarray Analysis Genes Genetic Genetic Polymorphism Genetic Recombination Genomics Goals Haplotypes Health Care Costs Hospitals Human Hypertension Inbred Strain Inbred Strains Mice Individual Infarction Ischemia Lead Maps Methods Middle Cerebral Artery Occlusion Modeling Monozygotic Twinning Monozygotic twins Mouse Strains Mus Mutation Pathogenesis Pathologic Patients Phenotype Predisposition Public Health Quantitative Trait Loci Research Resolution Resources Rodent Model Sequence Analysis Single Nucleotide Polymorphism Map Slide Stroke Surveys Susceptibility Gene Techniques Testing Therapeutic Time Tissue-Specific Gene Expression Twin Studies United States Variant Western Blotting Woman base comparative computer based statistical methods cost disability experience genetic linkage analysis genetic resource genome sequencing medical schools middle cerebral artery mortality mouse genome mouse model network models protein expression public health relevance response success tool trait

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中文摘要

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英文摘要

DESCRIPTION (provided by applicant): Stroke is the third leading cause of mortality and the leading cause of severe disability worldwide. It is a complex disease that results from many different pathologic conditions including atherosclerosis and hypertension and is therefore affected by multiple genetic and environmental factors. Understanding the genetic basis of stroke will allow us to gain a deeper understanding of the mechanisms behind its pathogenesis. As a complex disease trait, the genetic basis of stroke susceptibility can be studied by using quantitative trait loci analysis to identify regions of DNA that are associated with it. In this proposal, we aim to study the susceptibility to cerebral infarction in the presence of focal cerebral ischemia in mice via an integrative strain survey. We hypothesize that susceptibility to cerebral infarction in the presence of ischemia vary among inbred strains of mice and that this phenotypic variability across strains has a genetic basis. We will perform in silico QTL mapping (haplotype association mapping) for inbred strain phenotypes to identify potential chromosomal regions with stroke susceptibility genes. We will integrate the QTL results with that of microarray gene expression analysis and other bioinformatics tools to narrow down the QTL regions for selection of candidate genes causing stroke susceptibility. The single gene analysis will be extended to incorporate probabilistic gene networks. The candidate genes which affect the vulnerability to stroke as predicted by the QTL mapping can be applied to human studies and ultimately lead to therapeutic and predictive tools for cerebral protection in patients with a variety of cerebrovascular diseases. PUBLIC HEALTH RELEVANCE: Stroke is a major public health burden. This project uses a mouse model of stroke to examine the genetic basis of stroke susceptibility. This will be accomplished via computational and bioinformatics tools together with the emerging genetics resources.

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