Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'
Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'
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DOI：
10.1038/ng1497
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发表时间：
2005-03-01
期刊：
影响因子：
30.8
通讯作者：
de Haan, G
中科院分区：
文献类型：
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作者：
Bystrykh, L;Weersing, E;de Haan, G
我们结合大规模的mRNA表达分析和基因定位，以确定控制造血干细胞（HSC）功能的基因和位点。我们测量了从一组密集基因型重组近交系小鼠品系中分离的纯化HSC中的mRNA表达水平。我们绘制了与数千个转录本表达变异相关的数量性状基因座（QTL）。通过比较物理转录本的位置与控制QTL的位置，我们确定了多态性顺式作用干细胞基因。我们还确定了多个反式作用的控制基因座，修改大量的基因表达。这些共调节转录物组识别指定干细胞变异的途径。我们说明了这一概念与识别的候选基因参与HSC营业额。我们比较了来自相同小鼠的HSC和脑中的表达QTL，并鉴定了共享和组织特异性QTL。我们的数据可以通过WebQTL访问，WebQTL是一个基于网络的界面，允许自定义遗传连锁分析和识别共调节转录本。
We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue- specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.