Extreme context specificity in differential allelic expression
Extreme context specificity in differential allelic expression
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DOI：
10.1093/hmg/ddl488
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发表时间：
2007-03-01
影响因子：
3.5
通讯作者：
Loughlin, John
中科院分区：
文献类型：
--
作者：
Wilkins, James M.;Southam, Lorraine;Loughlin, John
基因表达顺式调控的变异性与包括常见多因子疾病在内的复杂性状的表型表现有关。由于顺式调控元件多态性导致的等位基因差异表达在人类基因组中很常见，但关于这些控制元件的上下文特异性的信息缺乏。在这项研究中，我们检测了BMP5的差异等位基因表达（DAE），这些基因来自16名接受关节置换治疗骨关节炎的供体。我们观察到BMP5等位基因输出的显著差异，在一些供者的组织中，等位基因比例大于4:1 （P < 10(-20)）。我们还发现了供体不同组织中等位基因表达的显著差异。对于我们的12个供体，我们检查了两个不同软骨区域BMP5的等位基因表达：骨关节炎病变部位附近的软骨和病变远端的软骨。这12个捐助者中有5个表现出高度显著的差异(P
Variability in cis-regulation of gene expression has been implicated in the phenotypic manifestation of complex traits including common, multifactorial diseases. The differential expression of alleles due to polymorphism in cis-regulatory elements is common in the human genome, but there is a paucity of information about the context specificity of these control elements. In this study, we examined the differential allelic expression (DAE) of BMP5 in human mesenchymal tissues obtained from 16 donors undergoing joint replacement for treatment of osteoarthritis. We observed significant differences in BMP5 allelic output, with allelic ratios greater than 4:1 (P < 10(-20)) in the tissues of some donors. We also discovered a significant variability in allelic expression within the different tissues of donors. For 12 of our donors, we examined the allelic expression of BMP5 in two different regions of cartilage: cartilage adjacent to the site of the osteoarthritic lesion and cartilage distal from the lesion. Five of these 12 donors demonstrated highly significant differences (P