Stroke genomics: Approaches to identify, validate, and understand ischemic stroke gene expression

被引:69
作者
Read, SJ
Parsons, AA
Harrison, DC
Philpott, K
Kabnick, K
O'Brien, S
Clark, S
Brawner, M
Bates, S
Gloger, I
Legos, JJ
Barone, FC
机构
[1] GlaxoSmithKline, Neurol Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England
[2] GlaxoSmithKline, Neurol Ctr Excellence Bioinformat, Harlow CM19 5AW, Essex, England
[3] GlaxoSmithKline, Neurol Ctr Excellence Genet Res, Harlow CM19 5AW, Essex, England
[4] GlaxoSmithKline, Neurol Ctr Excellence High Throughput Biol, Harlow CM19 5AW, Essex, England
[5] GlaxoSmithKline, King Of Prussia, PA 19406 USA
关键词
differential display; gene expression; MCAO; microarray gridding; neuroprotective genes; neurodestructive genes; protein; representative differential analysis; stroke; stroke in evolution; suppressive subtractive hybridization; target validation; transcription; translation;
D O I
10.1097/00004647-200107000-00001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Sequencing of the human genome is nearing completion and biologists, molecular biologists, and bioinformatics specialists have teamed up to develop global genomic technologies to help decipher the complex nature of pathophysiologic gene function. This review will focus on differential gene expression in ischemic stroke. It will discuss inheritance in the broader stroke population, how experimental models of spontaneous stroke might be applied to humans to identify chromosomal loci of increased risk and ischemic sensitivity, and also how the gene expression induced by stroke is related to the poststroke processes of brain injury, repair, and recovery. In addition, we discuss and summarise the literature of experimental stroke genomics and compare several approaches of differential gene expression analyzes. These in elude a comparison of representational difference analysis we have provided using an experimental stroke model that is representative of stroke evolution observed most often in man, and a summary of available data on stroke differential gene expression. Issues regarding validation of potential genes as stroke targets, the verification of message translation to protein products, the relevance of the expression of neuroprotective and neurodestructive genes and their Specific timings, and the emerging problems of handling novel genes that may be discovered covered during differential gene expression analyses will also be addressed.
引用
收藏
页码:755 / 778
页数:24
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