HapMap methylation-associated SNPs, markers of germline DNA methylation, positively correlate with regional levels of human meiotic recombination Export

@article{citeulike:3973269, abstract = {10.1101/gr.086181.108 Inter-individual and regional variability in recombination rates cannot be fully explained by the DNA sequence itself. Epigenetic mechanisms might be one additional factor affecting recombination. A biochemical approach to studying human germline methylation is difficult. We used the density of the 434,198 nonredundant methylation-associated SNPs (mSNPs) in the derived allele HapMap data set as a surrogate marker for germline DNA methylation. We validated our methodology by demonstrating that the mSNP density confirmed known patterns of genomic methylation, including the hypermutability of methylated cytosine and hypomethylation of CpG islands. Using this approach, we found a genome-wide positive correlation between germline methylation and regional recombination rate (500-kb windows: = 0.622, < 10). This remained significant with multiple correlations correcting for sequence features known to affect recombination, such as GC content and CpG dinucleotides (500-kb windows: = 0.172, < 10). Using the ENCODE data set for increased resolution, we found a positive correlation between germline DNA methylation and recombination rate (50-kb windows: = 0.301, = 0.002). This correlation was further strengthened when corrected for sequence features affecting recombination (50-kb windows: = 0.445, < 0.0001). In the Human Epigenome Project data set there was increased DNA methylation in regions within recombination hot spots in male germ cells (0.632 vs. 0.557, = 0.007). The relationship we observed between germline DNA methylation and recombination could be explained in two ways that are not mutually exclusive: DNA methylation could indicate preferred sites for recombination, or methylation following recombination could inhibit further recombination, perhaps by being part of the enigmatic molecular pathway mediating crossover interference.}, author = {Sigurdsson, Martin I. and Smith, Albert V. and Bjornsson, Hans T. and Jonsson, Jon J.}, citeulike-article-id = {3973269}, citeulike-linkout-0 = {http://dx.doi.org/10.1101/gr.086181.108}, citeulike-linkout-1 = {http://genome.cshlp.org/content/19/4/581.abstract}, citeulike-linkout-2 = {http://genome.cshlp.org/content/19/4/581.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19158364}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19158364}, day = {26}, doi = {10.1101/gr.086181.108}, issn = {1088-9051}, journal = {Genome Research}, keywords = {dna-methylation, epigenetics, germline, hapmap, iceland, recombination, snp}, month = {April}, number = {4}, pages = {581--589}, posted-at = {2009-01-28 13:46:14}, priority = {2}, title = {HapMap methylation-associated SNPs, markers of germline DNA methylation, positively correlate with regional levels of human meiotic recombination}, url = {http://dx.doi.org/10.1101/gr.086181.108}, volume = {19}, year = {2009} }

TY - JOUR ID - citeulike:3973269 L3 - citeulike-article-id:3973269 N2 - 10.1101/gr.086181.108 Inter-individual and regional variability in recombination rates cannot be fully explained by the DNA sequence itself. Epigenetic mechanisms might be one additional factor affecting recombination. A biochemical approach to studying human germline methylation is difficult. We used the density of the 434,198 nonredundant methylation-associated SNPs (mSNPs) in the derived allele HapMap data set as a surrogate marker for germline DNA methylation. We validated our methodology by demonstrating that the mSNP density confirmed known patterns of genomic methylation, including the hypermutability of methylated cytosine and hypomethylation of CpG islands. Using this approach, we found a genome-wide positive correlation between germline methylation and regional recombination rate (500-kb windows: = 0.622, < 10). This remained significant with multiple correlations correcting for sequence features known to affect recombination, such as GC content and CpG dinucleotides (500-kb windows: = 0.172, < 10). Using the ENCODE data set for increased resolution, we found a positive correlation between germline DNA methylation and recombination rate (50-kb windows: = 0.301, = 0.002). This correlation was further strengthened when corrected for sequence features affecting recombination (50-kb windows: = 0.445, < 0.0001). In the Human Epigenome Project data set there was increased DNA methylation in regions within recombination hot spots in male germ cells (0.632 vs. 0.557, = 0.007). The relationship we observed between germline DNA methylation and recombination could be explained in two ways that are not mutually exclusive: DNA methylation could indicate preferred sites for recombination, or methylation following recombination could inhibit further recombination, perhaps by being part of the enigmatic molecular pathway mediating crossover interference. IS - 4 JF - Genome Research SN - 1088-9051 EP - 589 TI - HapMap methylation-associated SNPs, markers of germline DNA methylation, positively correlate with regional levels of human meiotic recombination VL - 19 SP - 581 KW - dna-methylation KW - epigenetics KW - germline KW - hapmap KW - iceland KW - recombination KW - snp AU - Sigurdsson, Martin AU - Smith, Albert AU - Bjornsson, Hans AU - Jonsson, Jon PY - 2009/04/26/ UR - http://dx.doi.org/10.1101/gr.086181.108 ER -