A genome-wide view of mutation rate co-variation using multivariate analyses.
A genome-wide view of mutation rate co-variation using multivariate analyses.
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DOI：
10.1186/gb-2011-12-3-r27
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发表时间：
2011
期刊：
影响因子：
12.3
通讯作者：
Makova KD
中科院分区：
文献类型：
--
作者：
Ananda G;Chiaromonte F;Makova KD
虽然丰富的可用测序基因组已经导致了许多突变率区域异质性的研究，但不同突变率之间的共变异在很大程度上仍未被探索，阻碍了对突变和基因组动力学的更深入理解。本研究利用灵长类和啮齿动物基因组比对，采用两种多变量分析技术（主成分和典型相关）研究了四种突变类型的速率共变结构，同时探讨了不同基因组尺度和系统发育距离下多种基因组特征的关联。我们观察到核苷酸替换率，小插入率和小缺失率之间存在一致的，很大程度上线性共变，在染色体X和常染色体端粒附近检测到这些率之间存在一些非线性关联。这种共变异似乎是由一组共同的基因组特征形成的，其中一些是以前研究过的，一些是本研究的新特征（核层结合位点、甲基化的非cpg位点和核小体无区）。在大染色体的着丝粒附近的基因组特征之间也检测到强烈的非线性关系。微卫星突变率在更细的尺度上与其他突变率共同变化，但在1mb尺度上则不同，并且在不同尺度上与基因组特征表现出不同程度的关联。我们的结果使我们能够推测不同的分子机制，如复制、重组、修复和局部染色质环境，在诱变中的作用。为我们的分析开发的软件工具可通过开源基因组学门户网站Galaxy获得，以促进在未来大规模基因组学研究中使用多变量技术。
While the abundance of available sequenced genomes has led to many studies of regional heterogeneity in mutation rates, the co-variation among rates of different mutation types remains largely unexplored, hindering a deeper understanding of mutagenesis and genome dynamics. Here, utilizing primate and rodent genomic alignments, we apply two multivariate analysis techniques (principal components and canonical correlations) to investigate the structure of rate co-variation for four mutation types and simultaneously explore the associations with multiple genomic features at different genomic scales and phylogenetic distances. We observe a consistent, largely linear co-variation among rates of nucleotide substitutions, small insertions and small deletions, with some non-linear associations detected among these rates on chromosome X and near autosomal telomeres. This co-variation appears to be shaped by a common set of genomic features, some previously investigated and some novel to this study (nuclear lamina binding sites, methylated non-CpG sites and nucleosome-free regions). Strong non-linear relationships are also detected among genomic features near the centromeres of large chromosomes. Microsatellite mutability co-varies with other mutation rates at finer scales, but not at 1 Mb, and shows varying degrees of association with genomic features at different scales. Our results allow us to speculate about the role of different molecular mechanisms, such as replication, recombination, repair and local chromatin environment, in mutagenesis. The software tools developed for our analyses are available through Galaxy, an open-source genomics portal, to facilitate the use of multivariate techniques in future large-scale genomics studies.
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影响因子：
2.9
作者：
Amos W;Flint J;Xu X
通讯作者：
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影响因子：
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作者：
Boissinot, S;Entezam, A;Furano, AV
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作者：
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通讯作者：
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DOI：
10.1098/rspb.2009.1757
发表时间：
2010-05-07
影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
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