Gene expression variation in the adult human retina
Gene expression variation in the adult human retina
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DOI：
10.1093/hmg/ddg326
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发表时间：
2003-11-15
影响因子：
3.5
通讯作者：
Zack, DJ
中科院分区：
文献类型：
--
作者：
Chowers, I;Liu, DM;Zack, DJ
尽管有证据表明，基因表达水平的差异对各个个体的表型变异显着促进，但研究人体组织中基因表达变异的努力只有有限的努力。为了表征正常人视网膜中的表达变化，我们利用自定义的视网膜微阵列分析了来自29-90岁的19个捐助者的33个正常视网膜。统计模型旨在分离和量化变异的生物学和技术来源，包括年龄，性别，眼睛的横向性，基因功能和年龄相互作用。尽管所分析的9406个基因中的大多数显示出不同供体的表达水平相对稳定（对于平均基因而言，100个个体中95个表达水平值落在1.23倍范围内），但2.6％的基因显示出明显的供体对。 -donor变化，错误发现率为10％。平均表达比标准偏差为0.15 +/- 0.8，log（2），范围为0.09-0.99。在感光体中选择性表达的基因表现出比其他基因类别更高的表达变异。性别，年龄和其他供体特异性因素对多个基因的表达变异产生了重大贡献，并确定了具有年龄和性别相关的表达模式的基因组。我们的发现表明，正常人视网膜中基因表达变异的很大一部分归因于可识别的生物学因素。视网膜功能中心的许多基因（包括光感受器特异性基因）的较大表达变异性可以部分通过视觉过程的动力学来解释，并提高了光感受器基因表达水平可能有助于正常成年视网膜的表型多样性的可能性。另外，由于这种多样性可能导致疾病的易感性不同，因此探索其来源可能会提供对视网膜疾病发病机理的见解。
Despite evidence that differences in gene expression levels contribute significantly to phenotypic variation across individuals, there has been only limited effort to study gene expression variation in human tissue. To characterize expression variation in the normal human retina, we utilized a custom retinal microarray to analyze 33 normal retinas from 19 donors, aged 29-90 years. Statistical models were designed to separate and quantify biological and technical sources of variation, including age, gender, eye laterality, gene function and age-by-gender interaction. Although the majority of the 9406 genes analyzed showed relatively stable expression levels across different donors (for an average gene the expression level value of 95 out of a 100 individuals fell within a 1.23-fold range), 2.6% of genes showed significant donor-to-donor variation, with a false discovery rate of 10%. The mean expression ratio standard deviation was 0.15+/-0.8, log(2), with a range of 0.09-0.99. Genes selectively expressed in photoreceptors showed higher expression variation than other gene classes. Gender, age and other donor-specific factors contributed significantly to the expression variation of multiple genes, and groups of genes with an age- and gender-associated expression pattern were identified. Our findings show that a significant fraction of gene expression variation in the normal human retina is attributable to identifiable biological factors. The greater expression variability of many genes central to retinal function (including photoreceptor-specific genes) may be partially explained by the dynamics of the vision process, and raises the possibility that photoreceptor gene expression levels may contribute to phenotypic diversity across normal adult retinas. In addition, as such diversity may result in different levels of disease susceptibility, exploring its sources may provide insights into the pathogenesis of retinal disease.