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Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis 

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Presentation on theme: "Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis "— Presentation transcript:

1 Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis  Kenneth I. Aston, Ph.D., Vasu Punj, Ph.D., Lihua Liu, M.D., Douglas T. Carrell, Ph.D.  Fertility and Sterility  Volume 97, Issue 2, Pages e4 (February 2012) DOI: /j.fertnstert Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions

2 Figure 1 Illustration of the dramatic differences in methylation in samples E4, P9, and P10. (A) Heatmap of the top 607 most variable CpGs as identified by SD/SDmax, demonstrating the marked difference in methylation at a large number of CpGs in the three abnormal samples. Unmethylated CpGs are denoted by blue, and completely methylated CpGs are denoted by red. (B) Scatter plot of all samples plotted by the first two principal components. Principal components were calculated from methylation data across all CpGs. All controls and the majority of patient samples form a very tight cluster, whereas P9, P10, and E4 exhibit broad divergence from the main cluster. (C) Heatmap of all 140 imprinted-gene DMR CpGs identified on the chip, again demonstrating the marked difference in methylation at a significant proportion of CpGs in the three abnormal samples. Fertility and Sterility  , e4DOI: ( /j.fertnstert ) Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions

3 Figure 2 Functional groups overrepresented among the genes associated with differentially methylated loci in E4, P9, and P10. Threshold was set at P=.05, and the degree of significance is indicated as −log(P value) on the y-axis. Fertility and Sterility  , e4DOI: ( /j.fertnstert ) Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions

4 Figure 3 Average methylation levels at several imprinted gene DMRs for three controls (F1, F2, and F3) and three abnormally methylated samples (E4, P9, and P10), based on (A) HumanMethylation27 BeadChip data (the results illustrated are based on all probes within a 10-kb window centered about the pyrosequencing amplicon) and (B) bisulfite pyrosequencing data. Error bars represent SEM. Fertility and Sterility  , e4DOI: ( /j.fertnstert ) Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions

5 Supplemental Figure 1 Distribution of median β values, representing percentage methylation, across all CpGs analyzed by the HumanMethylation27 BeadChip. Fertility and Sterility  , e4DOI: ( /j.fertnstert ) Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions

6 Supplemental Figure 2 Functional groups overrepresented among the genes associated with differentially methylated loci in E4 compared with controls. Threshold was set at P=.05, and the degree of significance is indicated as −log(P value) on the y-axis. Fertility and Sterility  , e4DOI: ( /j.fertnstert ) Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions


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