Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter syndrome
SUMMARY Klinefelter syndrome (KS) (47 XXY) is a common sex‐chromosome aneuploidy with an estimated prevalence of one in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary...
Gespeichert in:
| Veröffentlicht in: | Molecular reproduction and development 2015-05, Vol.82 (5), p.377-386 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 386 |
|---|---|
| container_issue | 5 |
| container_start_page | 377 |
| container_title | Molecular reproduction and development |
| container_volume | 82 |
| creator | Wan, Emily S. Qiu, Weiliang Morrow, Jarrett Beaty, Terri H. Hetmanski, Jacqueline Make, Barry J. Lomas, David A. Silverman, Edwin K. DeMeo, Dawn L. |
| description | SUMMARY
Klinefelter syndrome (KS) (47 XXY) is a common sex‐chromosome aneuploidy with an estimated prevalence of one in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary X chromosome; systematic investigations of the epigenome have been limited. We obtained genome‐wide DNA methylation data from peripheral blood using the Illumina HumanMethylation450K platform in 5 KS (47 XXY) versus 102 male (46 XY) and 113 female (46 XX) control subjects participating in the COPDGene Study. Empirical Bayes‐mediated models were used to test for differential methylation by KS status. CpG sites with a false‐discovery rate |
| doi_str_mv | 10.1002/mrd.22483 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4439255</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1683352398</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5503-3cfe43e1cbc30a97abac3f87b44a887f307878dcd56cea726259176e276da45c3</originalsourceid><addsrcrecordid>eNqNks1u1DAUhSMEoqWw4AWQJTZs0jr-iZ0NEm3pgDoFaQSCneXYN4yLEw920um8fT2dMgJWrHyt-53rY_sUxcsKH1cYk5M-2mNCmKSPisMKN7IkouGPtzXDJePk-0HxLKVrjHHTSPy0OCC8kZILdlgsZzCEHsq1s4CSG6FMKzCucwZZ13UQYRid9qiHcbnxenRhQG5A4xJQ60OwKHR5b92Ns5P2Ca3duESX3g3QgR8horQZbMwnPC-edBmAFw_rUfH14v2Xsw_l_PPs49m7eWk4x7SkpgNGoTKtoVg3Qrfa0E6KljEtpegoFlJIayyvDWhB6nyVStRARG0144YeFW93c1dT24M12X_UXq2i63XcqKCd-rszuKX6EW4UY7QhnOcBbx4GxPBrgjSq3iUD3usBwpRUVUtKOaGN_B-UMFIzjDP6-h_0OkxxyC-xpSrSVJSRTL360_ze9e__ysDJDlg7D5t9v8JqGwSVg6Dug6CuFuf3RVaUO4VLI9zuFTr-VLWggqtvn2bq4vLqfDFfzNUpvQNmgbaT</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1681291342</pqid></control><display><type>article</type><title>Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter syndrome</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Wan, Emily S. ; Qiu, Weiliang ; Morrow, Jarrett ; Beaty, Terri H. ; Hetmanski, Jacqueline ; Make, Barry J. ; Lomas, David A. ; Silverman, Edwin K. ; DeMeo, Dawn L.</creator><creatorcontrib>Wan, Emily S. ; Qiu, Weiliang ; Morrow, Jarrett ; Beaty, Terri H. ; Hetmanski, Jacqueline ; Make, Barry J. ; Lomas, David A. ; Silverman, Edwin K. ; DeMeo, Dawn L.</creatorcontrib><description>SUMMARY
Klinefelter syndrome (KS) (47 XXY) is a common sex‐chromosome aneuploidy with an estimated prevalence of one in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary X chromosome; systematic investigations of the epigenome have been limited. We obtained genome‐wide DNA methylation data from peripheral blood using the Illumina HumanMethylation450K platform in 5 KS (47 XXY) versus 102 male (46 XY) and 113 female (46 XX) control subjects participating in the COPDGene Study. Empirical Bayes‐mediated models were used to test for differential methylation by KS status. CpG sites with a false‐discovery rate < 0.05 in the discovery cohort which were available on the first‐generation HumanMethylation 27 K platform were further examined in an independent replication cohort of 2 KS subjects, 590 male, and 495 female controls drawn from the International COPD Genetics Network (ICGN). Differential methylation at sites throughout the genome were identified, including 86 CpG sites that were differentially methylated in KS subjects relative to both male and female controls. CpG sites annotated to the HEN1 methyltransferase homolog 1 (HENMT1), calcyclin‐binding protein (CACYBP), and GTPase‐activating protein (SH3 domain)‐binding protein 1 (G3BP1) genes were among the “KS‐specific” loci that were replicated in ICGN. We conclude that site‐specific differential methylation exists throughout the genome in KS. The functional impact and clinical relevance of these differentially methylated loci should be explored in future studies. Mol. Reprod. Dev. 82: 377–386, 2015. © 2015 Wiley Periodicals, Inc.</description><identifier>ISSN: 1040-452X</identifier><identifier>EISSN: 1098-2795</identifier><identifier>DOI: 10.1002/mrd.22483</identifier><identifier>PMID: 25988574</identifier><identifier>CODEN: MREDEE</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Aged ; Blood Cells - metabolism ; Case-Control Studies ; CpG Islands - genetics ; DNA Methylation ; Epigenesis, Genetic ; Female ; Genome, Human ; Humans ; Klinefelter Syndrome - blood ; Klinefelter Syndrome - genetics ; Male ; Middle Aged ; Sex Factors</subject><ispartof>Molecular reproduction and development, 2015-05, Vol.82 (5), p.377-386</ispartof><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5503-3cfe43e1cbc30a97abac3f87b44a887f307878dcd56cea726259176e276da45c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmrd.22483$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmrd.22483$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25988574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wan, Emily S.</creatorcontrib><creatorcontrib>Qiu, Weiliang</creatorcontrib><creatorcontrib>Morrow, Jarrett</creatorcontrib><creatorcontrib>Beaty, Terri H.</creatorcontrib><creatorcontrib>Hetmanski, Jacqueline</creatorcontrib><creatorcontrib>Make, Barry J.</creatorcontrib><creatorcontrib>Lomas, David A.</creatorcontrib><creatorcontrib>Silverman, Edwin K.</creatorcontrib><creatorcontrib>DeMeo, Dawn L.</creatorcontrib><title>Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter syndrome</title><title>Molecular reproduction and development</title><addtitle>Mol. Reprod. Dev</addtitle><description>SUMMARY
Klinefelter syndrome (KS) (47 XXY) is a common sex‐chromosome aneuploidy with an estimated prevalence of one in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary X chromosome; systematic investigations of the epigenome have been limited. We obtained genome‐wide DNA methylation data from peripheral blood using the Illumina HumanMethylation450K platform in 5 KS (47 XXY) versus 102 male (46 XY) and 113 female (46 XX) control subjects participating in the COPDGene Study. Empirical Bayes‐mediated models were used to test for differential methylation by KS status. CpG sites with a false‐discovery rate < 0.05 in the discovery cohort which were available on the first‐generation HumanMethylation 27 K platform were further examined in an independent replication cohort of 2 KS subjects, 590 male, and 495 female controls drawn from the International COPD Genetics Network (ICGN). Differential methylation at sites throughout the genome were identified, including 86 CpG sites that were differentially methylated in KS subjects relative to both male and female controls. CpG sites annotated to the HEN1 methyltransferase homolog 1 (HENMT1), calcyclin‐binding protein (CACYBP), and GTPase‐activating protein (SH3 domain)‐binding protein 1 (G3BP1) genes were among the “KS‐specific” loci that were replicated in ICGN. We conclude that site‐specific differential methylation exists throughout the genome in KS. The functional impact and clinical relevance of these differentially methylated loci should be explored in future studies. Mol. Reprod. Dev. 82: 377–386, 2015. © 2015 Wiley Periodicals, Inc.</description><subject>Aged</subject><subject>Blood Cells - metabolism</subject><subject>Case-Control Studies</subject><subject>CpG Islands - genetics</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Female</subject><subject>Genome, Human</subject><subject>Humans</subject><subject>Klinefelter Syndrome - blood</subject><subject>Klinefelter Syndrome - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Sex Factors</subject><issn>1040-452X</issn><issn>1098-2795</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks1u1DAUhSMEoqWw4AWQJTZs0jr-iZ0NEm3pgDoFaQSCneXYN4yLEw920um8fT2dMgJWrHyt-53rY_sUxcsKH1cYk5M-2mNCmKSPisMKN7IkouGPtzXDJePk-0HxLKVrjHHTSPy0OCC8kZILdlgsZzCEHsq1s4CSG6FMKzCucwZZ13UQYRid9qiHcbnxenRhQG5A4xJQ60OwKHR5b92Ns5P2Ca3duESX3g3QgR8horQZbMwnPC-edBmAFw_rUfH14v2Xsw_l_PPs49m7eWk4x7SkpgNGoTKtoVg3Qrfa0E6KljEtpegoFlJIayyvDWhB6nyVStRARG0144YeFW93c1dT24M12X_UXq2i63XcqKCd-rszuKX6EW4UY7QhnOcBbx4GxPBrgjSq3iUD3usBwpRUVUtKOaGN_B-UMFIzjDP6-h_0OkxxyC-xpSrSVJSRTL360_ze9e__ysDJDlg7D5t9v8JqGwSVg6Dug6CuFuf3RVaUO4VLI9zuFTr-VLWggqtvn2bq4vLqfDFfzNUpvQNmgbaT</recordid><startdate>201505</startdate><enddate>201505</enddate><creator>Wan, Emily S.</creator><creator>Qiu, Weiliang</creator><creator>Morrow, Jarrett</creator><creator>Beaty, Terri H.</creator><creator>Hetmanski, Jacqueline</creator><creator>Make, Barry J.</creator><creator>Lomas, David A.</creator><creator>Silverman, Edwin K.</creator><creator>DeMeo, Dawn L.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QP</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201505</creationdate><title>Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter syndrome</title><author>Wan, Emily S. ; Qiu, Weiliang ; Morrow, Jarrett ; Beaty, Terri H. ; Hetmanski, Jacqueline ; Make, Barry J. ; Lomas, David A. ; Silverman, Edwin K. ; DeMeo, Dawn L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5503-3cfe43e1cbc30a97abac3f87b44a887f307878dcd56cea726259176e276da45c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Blood Cells - metabolism</topic><topic>Case-Control Studies</topic><topic>CpG Islands - genetics</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Female</topic><topic>Genome, Human</topic><topic>Humans</topic><topic>Klinefelter Syndrome - blood</topic><topic>Klinefelter Syndrome - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Sex Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wan, Emily S.</creatorcontrib><creatorcontrib>Qiu, Weiliang</creatorcontrib><creatorcontrib>Morrow, Jarrett</creatorcontrib><creatorcontrib>Beaty, Terri H.</creatorcontrib><creatorcontrib>Hetmanski, Jacqueline</creatorcontrib><creatorcontrib>Make, Barry J.</creatorcontrib><creatorcontrib>Lomas, David A.</creatorcontrib><creatorcontrib>Silverman, Edwin K.</creatorcontrib><creatorcontrib>DeMeo, Dawn L.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular reproduction and development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wan, Emily S.</au><au>Qiu, Weiliang</au><au>Morrow, Jarrett</au><au>Beaty, Terri H.</au><au>Hetmanski, Jacqueline</au><au>Make, Barry J.</au><au>Lomas, David A.</au><au>Silverman, Edwin K.</au><au>DeMeo, Dawn L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter syndrome</atitle><jtitle>Molecular reproduction and development</jtitle><addtitle>Mol. Reprod. Dev</addtitle><date>2015-05</date><risdate>2015</risdate><volume>82</volume><issue>5</issue><spage>377</spage><epage>386</epage><pages>377-386</pages><issn>1040-452X</issn><eissn>1098-2795</eissn><coden>MREDEE</coden><abstract>SUMMARY
Klinefelter syndrome (KS) (47 XXY) is a common sex‐chromosome aneuploidy with an estimated prevalence of one in every 660 male births. Investigations into the associations between DNA methylation and the highly variable clinical manifestations of KS have largely focused on the supernumerary X chromosome; systematic investigations of the epigenome have been limited. We obtained genome‐wide DNA methylation data from peripheral blood using the Illumina HumanMethylation450K platform in 5 KS (47 XXY) versus 102 male (46 XY) and 113 female (46 XX) control subjects participating in the COPDGene Study. Empirical Bayes‐mediated models were used to test for differential methylation by KS status. CpG sites with a false‐discovery rate < 0.05 in the discovery cohort which were available on the first‐generation HumanMethylation 27 K platform were further examined in an independent replication cohort of 2 KS subjects, 590 male, and 495 female controls drawn from the International COPD Genetics Network (ICGN). Differential methylation at sites throughout the genome were identified, including 86 CpG sites that were differentially methylated in KS subjects relative to both male and female controls. CpG sites annotated to the HEN1 methyltransferase homolog 1 (HENMT1), calcyclin‐binding protein (CACYBP), and GTPase‐activating protein (SH3 domain)‐binding protein 1 (G3BP1) genes were among the “KS‐specific” loci that were replicated in ICGN. We conclude that site‐specific differential methylation exists throughout the genome in KS. The functional impact and clinical relevance of these differentially methylated loci should be explored in future studies. Mol. Reprod. Dev. 82: 377–386, 2015. © 2015 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25988574</pmid><doi>10.1002/mrd.22483</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1040-452X |
| ispartof | Molecular reproduction and development, 2015-05, Vol.82 (5), p.377-386 |
| issn | 1040-452X 1098-2795 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4439255 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Aged Blood Cells - metabolism Case-Control Studies CpG Islands - genetics DNA Methylation Epigenesis, Genetic Female Genome, Human Humans Klinefelter Syndrome - blood Klinefelter Syndrome - genetics Male Middle Aged Sex Factors |
| title | Genome-wide site-specific differential methylation in the blood of individuals with Klinefelter syndrome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T13%3A19%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genome-wide%20site-specific%20differential%20methylation%20in%20the%20blood%20of%20individuals%20with%20Klinefelter%20syndrome&rft.jtitle=Molecular%20reproduction%20and%20development&rft.au=Wan,%20Emily%20S.&rft.date=2015-05&rft.volume=82&rft.issue=5&rft.spage=377&rft.epage=386&rft.pages=377-386&rft.issn=1040-452X&rft.eissn=1098-2795&rft.coden=MREDEE&rft_id=info:doi/10.1002/mrd.22483&rft_dat=%3Cproquest_pubme%3E1683352398%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1681291342&rft_id=info:pmid/25988574&rfr_iscdi=true |