Integrative DNA Methylation and Gene Expression Analyses Identify DNA Packaging and Epigenetic Regulatory Genes Associated with Low Motility Sperm
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{"title"=>"Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm", "type"=>"journal", "authors"=>[{"first_name"=>"Sara E.", "last_name"=>"Pacheco", "scopus_author_id"=>"42762082500"}, {"first_name"=>"E. Andres", "last_name"=>"Houseman", "scopus_author_id"=>"8335321500"}, {"first_name"=>"Brock C.", "last_name"=>"Christensen", "scopus_author_id"=>"8577632600"}, {"first_name"=>"Carmen J.", "last_name"=>"Marsit", "scopus_author_id"=>"6602980785"}, {"first_name"=>"Karl T.", "last_name"=>"Kelsey", "scopus_author_id"=>"7102336677"}, {"first_name"=>"Mark", "last_name"=>"Sigman", "scopus_author_id"=>"7102195988"}, {"first_name"=>"Kim", "last_name"=>"Boekelheide", "scopus_author_id"=>"7004822994"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-79957968811", "pui"=>"361877874", "doi"=>"10.1371/journal.pone.0020280", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"79957968811", "pmid"=>"21674046"}, "id"=>"17bdb4bb-682b-3f7b-a9ae-aa68e6854c0e", "abstract"=>"In previous studies using candidate gene approaches, low sperm count (oligospermia) has been associated with altered sperm mRNA content and DNA methylation in both imprinted and non-imprinted genes. We performed a genome-wide analysis of sperm DNA methylation and mRNA content to test for associations with sperm function.", "link"=>"http://www.mendeley.com/research/integrative-dna-methylation-gene-expression-analyses-identify-dna-packaging-epigenetic-regulatory-ge", "reader_count"=>84, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>8, "Researcher"=>26, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>5, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>8, "Researcher"=>26, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>1, "Other"=>3, "Student > Master"=>5, "Student > Bachelor"=>6, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>13, "Agricultural and Biological Sciences"=>48, "Medicine and Dentistry"=>12, "Neuroscience"=>1, "Computer Science"=>4}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>48}, "Computer Science"=>{"Computer Science"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>13}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Uruguay"=>1, "United States"=>1, "Japan"=>1, "Brazil"=>1, "Malaysia"=>1, "Spain"=>1, "Croatia"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/768736"], "description"=>"<p>The dendrograms above the heatmap show unsupervised clustering based on the methylation data alone, using a Euclidean metric with Ward's method of hierarchical clustering. Patients are represented by column (n = 21) and CpG loci by row (n = 616). Each cell represents the CpG level of methylation for one site in one sample. The methylation scale indicates the level of methylation: yellow = sample predominantly unmethylated (0–49% methylated); black = 50% of the sample is methylated; blue = sample predominantly methylated (51–100%). The column annotation track shows motility: orange = low, purple = high. The row annotation track shows type of imprinting: pink = maternally expressed, light blue = paternally expressed, light green = not determined.</p>", "links"=>[], "tags"=>["displaying", "methylation", "cpg", "loci", "imprinted"], "article_id"=>439099, "categories"=>["Cancer", "Genetics", "Developmental Biology"], "users"=>["Sara E. Pacheco", "E. Andres Houseman", "Brock C. Christensen", "Carmen J. Marsit", "Karl T. Kelsey", "Mark Sigman", "Kim Boekelheide"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020280.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Heatmap_displaying_the_methylation_status_of_CpG_loci_related_to_known_and_predicted_imprinted_genes_/439099", "title"=>"Heatmap displaying the methylation status of CpG loci related to known and predicted imprinted genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-06-02 02:31:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/769081"], "description"=>"<p>Note: Patients with * were excluded from the mRNA analysis due to low yield.</p>", "links"=>[], "tags"=>["parameters", "subjects"], "article_id"=>439445, "categories"=>["Cancer", "Genetics", "Developmental Biology"], "users"=>["Sara E. Pacheco", "E. Andres Houseman", "Brock C. Christensen", "Carmen J. Marsit", "Karl T. Kelsey", "Mark Sigman", "Kim Boekelheide"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020280.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Semen_Parameters_of_Subjects_Examined_/439445", "title"=>"Semen Parameters of Subjects Examined.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-06-02 02:37:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/769152"], "description"=>"<p>Note: # = Number of significantly altered loci in low motility samples; MS = methylation status of the loci; − = loci hypomethylated in low motility samples; + = loci hypermethylated in low motility samples; −/+ = more than two loci were altered and some of the loci were hypomethylated and some of were hypermethylated. Genes with * have been previously reported differentially methylated in sperm.</p>", "links"=>[], "tags"=>["spermatogenesis", "epigenetic", "aberrant", "dna"], "article_id"=>439522, "categories"=>["Cancer", "Genetics", "Developmental Biology"], "users"=>["Sara E. Pacheco", "E. Andres Houseman", "Brock C. Christensen", "Carmen J. Marsit", "Karl T. Kelsey", "Mark Sigman", "Kim Boekelheide"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020280.t003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genes_Associated_with_Spermatogenesis_and_Epigenetic_Regulation_with_Aberrant_DNA_Methylation_/439522", "title"=>"Genes Associated with Spermatogenesis and Epigenetic Regulation with Aberrant DNA Methylation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-06-02 02:38:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/386318", "https://ndownloader.figshare.com/files/386372", "https://ndownloader.figshare.com/files/386411", "https://ndownloader.figshare.com/files/392857"], "description"=>"<div><h3>Background</h3><p>In previous studies using candidate gene approaches, low sperm count (oligospermia) has been associated with altered sperm mRNA content and DNA methylation in both imprinted and non-imprinted genes. We performed a genome-wide analysis of sperm DNA methylation and mRNA content to test for associations with sperm function.</p> <h3>Methods and Results</h3><p>Sperm DNA and mRNA were isolated from 21 men with a range of semen parameters presenting to a tertiary male reproductive health clinic. DNA methylation was measured with the Illumina Infinium array at 27,578 CpG loci. Unsupervised clustering of methylation data differentiated the 21 sperm samples by their motility values. Recursively partitioned mixture modeling (RPMM) of methylation data resulted in four distinct methylation profiles that were significantly associated with sperm motility (<em>P</em> = 0.01). Linear models of microarray analysis (LIMMA) was performed based on motility and identified 9,189 CpG loci with significantly altered methylation (<em>Q</em><0.05) in the low motility samples. In addition, the majority of these disrupted CpG loci (80%) were hypomethylated. Of the aberrantly methylated CpGs, 194 were associated with imprinted genes and were almost equally distributed into hypermethylated (predominantly paternally expressed) and hypomethylated (predominantly maternally expressed) groups. Sperm mRNA was measured with the Human Gene 1.0 ST Affymetrix GeneChip Array. LIMMA analysis identified 20 candidate transcripts as differentially present in low motility sperm, including <em>HDAC1</em> (NCBI 3065), <em>SIRT3</em> (NCBI 23410), and <em>DNMT3A</em> (NCBI 1788). There was a trend among altered expression of these epigenetic regulatory genes and RPMM DNA methylation class.</p> <h3>Conclusions</h3><p>Using integrative genome-wide approaches we identified CpG methylation profiles and mRNA alterations associated with low sperm motility.</p> </div>", "links"=>[], "tags"=>["integrative", "dna", "methylation", "analyses", "packaging", "epigenetic", "genes", "motility", "sperm"], "article_id"=>136252, "categories"=>["Cancer", "Genetics", "Developmental Biology"], "users"=>["Sara E. Pacheco", "E. Andres Houseman", "Brock C. Christensen", "Carmen J. Marsit", "Karl T. Kelsey", "Mark Sigman", "Kim Boekelheide"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0020280.s001", "https://dx.doi.org/10.1371/journal.pone.0020280.s002", "https://dx.doi.org/10.1371/journal.pone.0020280.s003", "https://dx.doi.org/10.1371/journal.pone.0020280.s004"], "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Integrative_DNA_Methylation_and_Gene_Expression_Analyses_Identify_DNA_Packaging_and_Epigenetic_Regulatory_Genes_Associated_with_Low_Motility_Sperm/136252", "title"=>"Integrative DNA Methylation and Gene Expression Analyses Identify DNA Packaging and Epigenetic Regulatory Genes Associated with Low Motility Sperm", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-06-02 01:44:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/769116"], "description"=>"<p>Note: E = parent with expressed allele; # = number of significantly altered loci in low motility samples; MS = methylation status of the loci; M = maternally expressed; P = paternally expressed; N = parent of origin not determined; − = loci hypomethylated in low motility samples; + = loci hypermethylated in low motility samples; −/+ = more than two loci were altered and some of the loci were hypomethylated and some of were hypermethylated. Genes with * have been previously reported differentially methylated in sperm.</p>", "links"=>[], "tags"=>["genes", "aberrant", "dna"], "article_id"=>439481, "categories"=>["Cancer", "Genetics", "Developmental Biology"], "users"=>["Sara E. Pacheco", "E. Andres Houseman", "Brock C. Christensen", "Carmen J. Marsit", "Karl T. Kelsey", "Mark Sigman", "Kim Boekelheide"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020280.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Imprinted_Genes_with_Aberrant_DNA_Methylation_/439481", "title"=>"Imprinted Genes with Aberrant DNA Methylation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-06-02 02:38:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/768990"], "description"=>"<p>Each panel of boxplots (A–C) compares expression data for a particular gene: (A) <i>HDAC1</i>; (B) <i>SIRT3</i>; and (C) <i>DNMT3A</i>. The x-axis represents RPMM classes. The y-axis represents normalized gene expression values (NEV).</p>", "links"=>[], "tags"=>["comparing", "dna", "methylation", "profiles", "epigenetic"], "article_id"=>439351, "categories"=>["Cancer", "Genetics", "Developmental Biology"], "users"=>["Sara E. Pacheco", "E. Andres Houseman", "Brock C. Christensen", "Carmen J. Marsit", "Karl T. Kelsey", "Mark Sigman", "Kim Boekelheide"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020280.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Boxplots_comparing_DNA_methylation_profiles_and_gene_expression_values_for_the_3_epigenetic_regulators_/439351", "title"=>"Boxplots comparing DNA methylation profiles and gene expression values for the 3 epigenetic regulators.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-06-02 02:35:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/768902"], "description"=>"<p>(A) RPMM displaying 1,000 most variable CpGs by class. Each column represents a class generated by RPMM (left left (LL), left right (LR), right left (RL), and right right (RR)). The width of the column represents the number of patients distributed in that class. The rows represent the average beta values for each CpG within the class. The methylation scale indicates the level of methylation: yellow = sample predominantly unmethylated (0–49% methylated); black = 50% of the sample is methylated; blue = sample predominantly methylated (51–100%).(B) Boxplot comparing the motility values for each class.</p>", "links"=>[], "tags"=>["genetics and genomics", "urology", "developmental biology"], "article_id"=>439268, "categories"=>["Cancer", "Genetics", "Developmental Biology"], "users"=>["Sara E. Pacheco", "E. Andres Houseman", "Brock C. Christensen", "Carmen J. Marsit", "Karl T. Kelsey", "Mark Sigman", "Kim Boekelheide"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020280.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RPMM_classes_/439268", "title"=>"RPMM classes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-06-02 02:34:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/768516"], "description"=>"<p>The dendrograms above the heatmap show unsupervised clustering based on the methylation data alone, using a Euclidean metric with Ward's method of hierarchical clustering. Patients are represented by column (n = 21) and CpG loci (n = 1000) by row. Each cell represents the CpG level of methylation for one site in one sample. The methylation scale indicates the level of methylation: yellow = sample predominantly unmethylated (0–49% methylated); black = 50% of the sample is methylated; blue = sample predominantly methylated (51–100%). The column annotation track shows motility: orange = low, purple = high.</p>", "links"=>[], "tags"=>["clustering", "cpg", "loci", "beta"], "article_id"=>438879, "categories"=>["Cancer", "Genetics", "Developmental Biology"], "users"=>["Sara E. Pacheco", "E. Andres Houseman", "Brock C. Christensen", "Carmen J. Marsit", "Karl T. Kelsey", "Mark Sigman", "Kim Boekelheide"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0020280.g001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Unsupervised_clustering_of_the_1_000_most_variable_CpG_loci_average_beta_values_/438879", "title"=>"Unsupervised clustering of the 1,000 most variable CpG loci average beta values.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-06-02 02:27:59"}

PMC Usage Stats | Further Information

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