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Nature:发育过程中基因表达的变化

 

    影响基因表达水平的多态性在很多物种中已通过“表达量化性状位点” (eQTL) 分析方法被发现。

    这项研究(集中在一个12小时的时段中对线虫所做的研究)让我们第一次全面地看到了这些多态性在发育过程中是怎样影响基因表达的动态的。

    顺式和反式eQTL都能增加和降低基因表达,具体情况取决于所分析的时间点,同时反式eQTL在一个给定的发育时段还能起表达的修饰因子的作用。

    希望这项研究中所建立的方法可用来研究其他动态过程,如生理和疾病发展。

基尼亚推荐的英文摘要)

Nature           doi:10.1038/nature12772

The effects of genetic variation on gene expression dynamics during development

Mirko Francesconi  & Ben Lehner

The development of a multicellular organism and physiological responses require massive coordinated changes in gene expression across several cell and tissue types1, 2, 3. Polymorphic regions of the genome that influence gene expression levels have been identified by expression quantitative trait locus (eQTL) mapping in many species4, 5, 6, including loci that have cell-dependent7, 8, tissue-dependent9 and age-dependent10 effects. However, there has been no comprehensive characterization of how polymorphisms influence the complex dynamic patterns of gene expression that occur during development and in physiology. Here we describe an efficient experimental design to infer gene expression dynamics from single expression profiles in different genotypes, and apply it to characterize the effect of local (cis) and distant (trans) genetic variation on gene expression at high temporal resolution throughout a 12-hour period of the development of Caenorhabditis elegans. Taking dynamic variation into account identifies >50% more cis-eQTLs, including more than 900 that alter the dynamics of expression during this period. Local sequence polymorphisms extensively affect the timing, rate, magnitude and shape of expression changes. Indeed, many local sequence variants both increase and decrease gene expression, depending on the time-point profiled. Expression dynamics during this 12-hour period are also influenced extensively in trans by distal loci. In particular, several trans loci influence genes with quite diverse dynamic expression patterns, but they do so primarily during a common time interval. Trans loci can therefore act as modifiers of expression during a particular period of development. This study provides the first characterization, to our knowledge, of the effect of local and distant genetic variation on the dynamics of gene expression throughout an extensive time period. Moreover, the approach developed here should facilitate the genetic dissection of other dynamic processes, including potentially development, physiology and disease progression in humans.

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