Genetic determinants of mitochondrial content
Genetic determinants of mitochondrial content
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DOI：
10.1093/hmg/ddm101
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发表时间：
2007-06-15
影响因子：
3.5
通讯作者：
Blangero, John
中科院分区：
文献类型：
--
作者：
Curran, Joanne E.;Johnson, Matthew P.;Blangero, John
线粒体是产生能量和呼吸的主要细胞部位。最近的研究集中在研究线粒体在疾病发展中的作用，越来越明显的是，线粒体功能障碍导致了各种人类疾病。线粒体DNA(MtDNA)含量对维持线粒体功能和满足人体能量需求非常重要。我们测量了1259名墨西哥裔美国人(来自42个大家庭)的线粒体含量，并表明mtDNA数量(线粒体完整性的替代衡量标准)具有很大的遗传成分。我们进行了基因组扫描和全基因组定量转录扫描，以确定影响线粒体含量的QTL。利用439个STR标记，采用基于变异成分连锁的基因组扫描方法，在10q染色体上定位了一个线粒体含量的QTL(LOD=3.83)。还检测到与线粒体基因组显著连锁的线粒体传递(LOD=3.39)。为了复制，我们测量了一个独立的高加索人群(1088人)的线粒体含量，以寻找在这些相同区域存在联系的证据。作为圣安东尼奥家庭心脏研究的一部分，我们获得了1240个个体的全基因组定量转录图谱。利用淋巴细胞样本，我们对20413个转录本进行了定量，并使用方差成分方法检验了这些转录本的表达水平与线粒体含量之间的相关性。利用考虑到残留遗传成分的回归分析，我们确定了829个影响线粒体含量的转录本(包括许多新基因)，这些转录本在从细胞信号到细胞运输和离子结合的一般生物学作用上有所不同。
The mitochondria are the major cellular site of energy production and respiration. Recent research has focused on investigating the role of mitochondria in disease development and it has become increasingly evident that mitochondrial dysfunction contributes to a variety of human diseases. Mitochondrial DNA (mtDNA) quantity is very important for maintaining mitochondrial function and meeting the energy needs of the body. We have measured mitochondrial content in 1259 Mexican American individuals (from 42 extended families) and have shown that mtDNA quantity (a surrogate measure of mitochondrial integrity) has a large genetic component. We performed a genome scan and a genome-wide quantitative transcriptomic scan to identify QTLs influencing mitochondrial content. A variance components linkage-based genome scan utilizing 439 STR markers was used to localize a QTL for mitochondrial content on chromosome 10q (LOD = 3.83). Significant linkage to the mitochondrial genome was also detected for mitochondrial transmission (LOD = 3.39). For replication, we measured mitochondrial content in an independent Caucasian population (1088 individuals) finding evidence for linkage in these same regions. As part of the San Antonio Family Heart Study, we obtained genome-wide quantitative transcriptional profiles from 1240 individuals. Using lymphocyte samples, we quantitated 20 413 transcripts and examined correlations between the expression levels of these transcripts and mitochondrial content using the variance components method. Using regression analysis allowing for residual genetic components, we identified 829 transcripts (including many novel genes) influencing mitochondrial content that vary in their general biological actions, from cell signaling to cell trafficking and ion binding.