Genetic analysis of genome-wide variation in human gene expression
Genetic analysis of genome-wide variation in human gene expression
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DOI：
10.1038/nature02797
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发表时间：
2004-08-12
期刊：
影响因子：
64.8
通讯作者：
Cheung, VG
中科院分区：
文献类型：
--
作者：
Morley, M;Molony, CM;Cheung, VG
基因表达的自然变异在人类和其他生物中广泛存在，许多基因的基线表达水平的变异具有可遗传成分。为了定位人类这些数量性状（表达表型）的遗传决定因素，我们使用微阵列来测量基因表达水平，并对14个大家族中3554个基因的表达水平进行全基因组连锁分析。对于大约1000种表达表型，有明显的证据表明与特定染色体区域存在连锁。顺式和反式作用位点都调节基因表达水平的变异，尽管大多数为反式作用。许多基因表达表型受若干遗传决定因素的影响。此外，我们发现了转录调控热点，其中几种表达表型（多达31种）的连锁明显证据相吻合，并且许多共享同一调控区域的基因的表达水平显著相关。用于表型分析的微阵列技术和用于数量性状的连锁分析相结合，使得能够对导致人类基因表达变异的决定因素进行遗传定位。
Natural variation in gene expression is extensive in humans and other organisms, and variation in the baseline expression level of many genes has a heritable component. To localize the genetic determinants of these quantitative traits ( expression phenotypes) in humans, we used microarrays to measure gene expression levels and performed genome-wide linkage analysis for expression levels of 3,554 genes in 14 large families. For approximately 1,000 expression phenotypes, there was significant evidence of linkage to specific chromosomal regions. Both cis- and trans-acting loci regulate variation in the expression levels of genes, although most act in trans. Many gene expression phenotypes are influenced by several genetic determinants. Furthermore, we found hotspots of transcriptional regulation where significant evidence of linkage for several expression phenotypes ( up to 31) coincides, and expression levels of many genes that share the same regulatory region are significantly correlated. The combination of microarray techniques for phenotyping and linkage analysis for quantitative traits allows the genetic mapping of determinants that contribute to variation in human gene expression.