DNA variation and brain region-specific expression profiles exhibit different relationships between inbred mouse strains: implications for eQTL mapping studies.
DNA variation and brain region-specific expression profiles exhibit different relationships between inbred mouse strains: implications for eQTL mapping studies.
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DNA变异和脑区域特异性表达谱图在近交小鼠菌株之间表现出不同的关系：对EQTL映射研究的影响。
DOI：
10.1186/gb-2007-8-2-r25
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Barlow, Carrolee
中科院分区：
文献类型：
--
作者：
Hovatta, Iiris;Zapala, Matthew A.;Broide, Ron S.;Schadt, Eric E.;Libiger, Ondrej;Schork, Nicholas J.;Lockhart, David J.;Barlow, Carrolee
来自6个近交系小鼠品系的5个脑区的基因表达谱表明，许多调控网络对特定脑区具有高度特异性。
表达数量性状基因座（eQTL）定位用于寻找对特定基因转录活性负责的基因座。在近期的eQTL研究中，表达谱要么来自匀浆化的全脑，要么来自大的脑区集合。然而，大脑是一个非常异质的器官，不同脑区的表达谱差异显著。由于eQTL研究在识别调控网络方面的重要性和潜在作用，我们分析了来自多个近交系小鼠品系不同脑区的基因表达模式，并研究了其对eQTL研究设计和分析的影响。
对6个近交系小鼠品系的5个脑区的基因表达谱进行了研究。很少有基因表现出显著的品系特异性表达模式，而大量基因表现出脑区特异性模式。我们根据品系之间的表达关系构建了系统发育树，并将其与DNA水平的关系树进行了比较。基于品系特异性基因表达的树在不同脑区是恒定的，并且反映了DNA水平的变异。然而，基于区域特异性基因的树根据脑区的不同呈现出不同的品系关系集。一项eQTL分析表明，在品系特异性基因中顺式作用调节因子富集，而脑区特异性基因似乎主要由反式作用元件调控。
我们的结果表明，许多调控网络具有高度的脑区特异性，并表明使用与感兴趣的性状在生理和表型上相关的脑区或组织的数据进行eQTL定位研究的重要性。
Gene expression profiles of five brain regions from six inbred mouse strains suggest that many regulatory networks are highly specific to particular brain regions. Expression quantitative trait locus (eQTL) mapping is used to find loci that are responsible for the transcriptional activity of a particular gene. In recent eQTL studies, expression profiles were derived from either homogenized whole brain or collections of large brain regions. However, the brain is a very heterogeneous organ, and expression profiles of different brain regions vary significantly. Because of the importance and potential power of eQTL studies in identifying regulatory networks, we analyzed gene expression patterns in different brain regions from multiple inbred mouse strains and investigated the implications for the design and analysis of eQTL studies. Gene expression profiles of five brain regions in six inbred mouse strains were studied. Few genes exhibited a significant strain-specific expression pattern, whereas a large number of genes exhibited brain region-specific patterns. We constructed phylogenetic trees based on the expression relationships between the strains and compared them with a DNA-level relationship tree. The trees based on the expression of strain-specific genes were constant across brain regions and mirrored DNA-level variation. However, the trees based on region-specific genes exhibited a different set of strain relationships, depending on the brain region. An eQTL analysis showed enrichment of cis-acting regulators among strain-specific genes, whereas brain region-specific genes appear to be mainly regulated by trans-acting elements. Our results suggest that many regulatory networks are highly brain region specific and indicate the importance of conducting eQTL mapping studies using data from brain regions or tissues that are physiologically and phenotypically relevant to the trait of interest.
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影响因子：
9.8
作者：
Pletcher MT;McClurg P;Batalov S;Su AI;Barnes SW;Lagler E;Korstanje R;Wang X;Nusskern D;Bogue MA;Mural RJ;Paigen B;Wiltshire T
通讯作者：
Wiltshire T
影响因子：
7
作者：
Ronald, J;Akey, JM;Kruglyak, L
通讯作者：
Kruglyak, L
影响因子：
7
作者：
Witmer, PD;Doheny, KF;Brownstein, MJ
通讯作者：
Brownstein, MJ
影响因子：
64.8
作者：
Hovatta, I;Tennant, RS;Barlow, C
通讯作者：
Barlow, C
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y