tailieunhanh - Báo cáo y học: "A genome-wide view of mutation rate co-variation using multivariate analyses"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: A genome-wide view of mutation rate co-variation using multivariate analyses. | Ananda et al. Genome Biology 2011 12 R27 http 2011 12 3 R27 Genome Biology RESEARCH Open Access A genome-wide view of mutation rate eo-variation using multivariate analyses Guruprasad Ananda1 2 Francesca Chiaromonte1 3 3 and Kateryna D Makova1 4 3 Abstract Background 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. Results 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. Conclusions 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 .