No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins
Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide a...
Gespeichert in:
| Veröffentlicht in: | PLoS genetics 2015-01, Vol.11 (1), p.e1004852 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 1 |
| container_start_page | e1004852 |
| container_title | PLoS genetics |
| container_volume | 11 |
| creator | Murdoch, John D Gupta, Abha R Sanders, Stephan J Walker, Michael F Keaney, John Fernandez, Thomas V Murtha, Michael T Anyanwu, Samuel Ober, Gordon T Raubeson, Melanie J DiLullo, Nicholas M Villa, Natalie Waqar, Zainabdul Sullivan, Catherine Gonzalez, Luis Willsey, A Jeremy Choe, So-Yeon Neale, Benjamin M Daly, Mark J State, Matthew W |
| description | Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk. |
| doi_str_mv | 10.1371/journal.pgen.1004852 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1685137702</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A418343218</galeid><doaj_id>oai_doaj_org_article_032f22b95c454267af5fad02cfa2ee09</doaj_id><sourcerecordid>A418343218</sourcerecordid><originalsourceid>FETCH-LOGICAL-c565t-f0056aa577eb75c2f21de450c69299959c18c499d6a0abe4475d54a4ec7727e13</originalsourceid><addsrcrecordid>eNp9Ul2LGyEUHUpLdzftPyit0JctNKk6OsaXQgj9WAjZfdg-i3GuiWlGgzpbtj-sv69mkw0bKEXQy_Wcc6_XU1VvCB6RWpBP69BHrzej7RL8iGDMxpw-q84J5_VQMMyeP4nPqouU1hjXfCzFy-qM8oYSKdh59WceENy5FrwBZENEOqVgnM4ueBQs0n12qUO_XF6hqCOgFWSI4ff9MvQJbYPzGXV9fsAn5DyaBp-1yc4PJwclaNFNDBlKauZ-AqLocjq_nU9u6IePqFQspOu8gvhfatohj4D0qnph9SbB68M5qH58_XI7_T6cXX-7mk5mQ8MbnocWY95ozYWAheCGWkpaYBybRlIpJZeGjA2Tsm001gtgTPCWM83ACEEFkHpQvdvrbjchqcPIkyLNmJdPEJgWxNUe0Qa9VtvoOh3vVdBOPSRCXCodszMbULguDdCF5IZxRhuhLbe6xdRYTQGwLFqfD9X6RQetAZ-j3pyInt54t1LLcKdYjRvOdu2-3wssdannvA0FZjqXjJowMq5ZTcs-qEb_QJXVQudM8GBdyZ8Q2J5gYkgpgj22RLDamfFxMmpnRnUwY6G9ffqcI-nRffVfy4jfyw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Public Library of Science (PLoS)</source><creator>Murdoch, John D ; Gupta, Abha R ; Sanders, Stephan J ; Walker, Michael F ; Keaney, John ; Fernandez, Thomas V ; Murtha, Michael T ; Anyanwu, Samuel ; Ober, Gordon T ; Raubeson, Melanie J ; DiLullo, Nicholas M ; Villa, Natalie ; Waqar, Zainabdul ; Sullivan, Catherine ; Gonzalez, Luis ; Willsey, A Jeremy ; Choe, So-Yeon ; Neale, Benjamin M ; Daly, Mark J ; State, Matthew W</creator><creatorcontrib>Murdoch, John D ; Gupta, Abha R ; Sanders, Stephan J ; Walker, Michael F ; Keaney, John ; Fernandez, Thomas V ; Murtha, Michael T ; Anyanwu, Samuel ; Ober, Gordon T ; Raubeson, Melanie J ; DiLullo, Nicholas M ; Villa, Natalie ; Waqar, Zainabdul ; Sullivan, Catherine ; Gonzalez, Luis ; Willsey, A Jeremy ; Choe, So-Yeon ; Neale, Benjamin M ; Daly, Mark J ; State, Matthew W</creatorcontrib><description>Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1004852</identifier><identifier>PMID: 25621974</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Autism ; Autistic Disorder - genetics ; Autistic Disorder - pathology ; Codon, Nonsense ; Contactins - genetics ; DNA Copy Number Variations ; Gene expression ; Gene mutation ; Genes ; Genetic aspects ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Identification and classification ; Membrane Proteins - genetics ; Mutation ; Nerve Tissue Proteins - genetics ; Point Mutation ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Sequence Deletion ; Studies</subject><ispartof>PLoS genetics, 2015-01, Vol.11 (1), p.e1004852</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Murdoch et al 2015 Murdoch et al</rights><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: ), or in Other Contactin-Associated Proteins or Contactins. PLoS Genet 11(1): e1004852. doi:10.1371/journal.pgen.1004852</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c565t-f0056aa577eb75c2f21de450c69299959c18c499d6a0abe4475d54a4ec7727e13</citedby><cites>FETCH-LOGICAL-c565t-f0056aa577eb75c2f21de450c69299959c18c499d6a0abe4475d54a4ec7727e13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306541/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306541/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25621974$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Murdoch, John D</creatorcontrib><creatorcontrib>Gupta, Abha R</creatorcontrib><creatorcontrib>Sanders, Stephan J</creatorcontrib><creatorcontrib>Walker, Michael F</creatorcontrib><creatorcontrib>Keaney, John</creatorcontrib><creatorcontrib>Fernandez, Thomas V</creatorcontrib><creatorcontrib>Murtha, Michael T</creatorcontrib><creatorcontrib>Anyanwu, Samuel</creatorcontrib><creatorcontrib>Ober, Gordon T</creatorcontrib><creatorcontrib>Raubeson, Melanie J</creatorcontrib><creatorcontrib>DiLullo, Nicholas M</creatorcontrib><creatorcontrib>Villa, Natalie</creatorcontrib><creatorcontrib>Waqar, Zainabdul</creatorcontrib><creatorcontrib>Sullivan, Catherine</creatorcontrib><creatorcontrib>Gonzalez, Luis</creatorcontrib><creatorcontrib>Willsey, A Jeremy</creatorcontrib><creatorcontrib>Choe, So-Yeon</creatorcontrib><creatorcontrib>Neale, Benjamin M</creatorcontrib><creatorcontrib>Daly, Mark J</creatorcontrib><creatorcontrib>State, Matthew W</creatorcontrib><title>No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk.</description><subject>Autism</subject><subject>Autistic Disorder - genetics</subject><subject>Autistic Disorder - pathology</subject><subject>Codon, Nonsense</subject><subject>Contactins - genetics</subject><subject>DNA Copy Number Variations</subject><subject>Gene expression</subject><subject>Gene mutation</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Membrane Proteins - genetics</subject><subject>Mutation</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Point Mutation</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Sequence Analysis, DNA</subject><subject>Sequence Deletion</subject><subject>Studies</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNp9Ul2LGyEUHUpLdzftPyit0JctNKk6OsaXQgj9WAjZfdg-i3GuiWlGgzpbtj-sv69mkw0bKEXQy_Wcc6_XU1VvCB6RWpBP69BHrzej7RL8iGDMxpw-q84J5_VQMMyeP4nPqouU1hjXfCzFy-qM8oYSKdh59WceENy5FrwBZENEOqVgnM4ueBQs0n12qUO_XF6hqCOgFWSI4ff9MvQJbYPzGXV9fsAn5DyaBp-1yc4PJwclaNFNDBlKauZ-AqLocjq_nU9u6IePqFQspOu8gvhfatohj4D0qnph9SbB68M5qH58_XI7_T6cXX-7mk5mQ8MbnocWY95ozYWAheCGWkpaYBybRlIpJZeGjA2Tsm001gtgTPCWM83ACEEFkHpQvdvrbjchqcPIkyLNmJdPEJgWxNUe0Qa9VtvoOh3vVdBOPSRCXCodszMbULguDdCF5IZxRhuhLbe6xdRYTQGwLFqfD9X6RQetAZ-j3pyInt54t1LLcKdYjRvOdu2-3wssdannvA0FZjqXjJowMq5ZTcs-qEb_QJXVQudM8GBdyZ8Q2J5gYkgpgj22RLDamfFxMmpnRnUwY6G9ffqcI-nRffVfy4jfyw</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Murdoch, John D</creator><creator>Gupta, Abha R</creator><creator>Sanders, Stephan J</creator><creator>Walker, Michael F</creator><creator>Keaney, John</creator><creator>Fernandez, Thomas V</creator><creator>Murtha, Michael T</creator><creator>Anyanwu, Samuel</creator><creator>Ober, Gordon T</creator><creator>Raubeson, Melanie J</creator><creator>DiLullo, Nicholas M</creator><creator>Villa, Natalie</creator><creator>Waqar, Zainabdul</creator><creator>Sullivan, Catherine</creator><creator>Gonzalez, Luis</creator><creator>Willsey, A Jeremy</creator><creator>Choe, So-Yeon</creator><creator>Neale, Benjamin M</creator><creator>Daly, Mark J</creator><creator>State, Matthew W</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150101</creationdate><title>No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins</title><author>Murdoch, John D ; Gupta, Abha R ; Sanders, Stephan J ; Walker, Michael F ; Keaney, John ; Fernandez, Thomas V ; Murtha, Michael T ; Anyanwu, Samuel ; Ober, Gordon T ; Raubeson, Melanie J ; DiLullo, Nicholas M ; Villa, Natalie ; Waqar, Zainabdul ; Sullivan, Catherine ; Gonzalez, Luis ; Willsey, A Jeremy ; Choe, So-Yeon ; Neale, Benjamin M ; Daly, Mark J ; State, Matthew W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c565t-f0056aa577eb75c2f21de450c69299959c18c499d6a0abe4475d54a4ec7727e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Autism</topic><topic>Autistic Disorder - genetics</topic><topic>Autistic Disorder - pathology</topic><topic>Codon, Nonsense</topic><topic>Contactins - genetics</topic><topic>DNA Copy Number Variations</topic><topic>Gene expression</topic><topic>Gene mutation</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Membrane Proteins - genetics</topic><topic>Mutation</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Point Mutation</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Sequence Analysis, DNA</topic><topic>Sequence Deletion</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Murdoch, John D</creatorcontrib><creatorcontrib>Gupta, Abha R</creatorcontrib><creatorcontrib>Sanders, Stephan J</creatorcontrib><creatorcontrib>Walker, Michael F</creatorcontrib><creatorcontrib>Keaney, John</creatorcontrib><creatorcontrib>Fernandez, Thomas V</creatorcontrib><creatorcontrib>Murtha, Michael T</creatorcontrib><creatorcontrib>Anyanwu, Samuel</creatorcontrib><creatorcontrib>Ober, Gordon T</creatorcontrib><creatorcontrib>Raubeson, Melanie J</creatorcontrib><creatorcontrib>DiLullo, Nicholas M</creatorcontrib><creatorcontrib>Villa, Natalie</creatorcontrib><creatorcontrib>Waqar, Zainabdul</creatorcontrib><creatorcontrib>Sullivan, Catherine</creatorcontrib><creatorcontrib>Gonzalez, Luis</creatorcontrib><creatorcontrib>Willsey, A Jeremy</creatorcontrib><creatorcontrib>Choe, So-Yeon</creatorcontrib><creatorcontrib>Neale, Benjamin M</creatorcontrib><creatorcontrib>Daly, Mark J</creatorcontrib><creatorcontrib>State, Matthew W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Murdoch, John D</au><au>Gupta, Abha R</au><au>Sanders, Stephan J</au><au>Walker, Michael F</au><au>Keaney, John</au><au>Fernandez, Thomas V</au><au>Murtha, Michael T</au><au>Anyanwu, Samuel</au><au>Ober, Gordon T</au><au>Raubeson, Melanie J</au><au>DiLullo, Nicholas M</au><au>Villa, Natalie</au><au>Waqar, Zainabdul</au><au>Sullivan, Catherine</au><au>Gonzalez, Luis</au><au>Willsey, A Jeremy</au><au>Choe, So-Yeon</au><au>Neale, Benjamin M</au><au>Daly, Mark J</au><au>State, Matthew W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>11</volume><issue>1</issue><spage>e1004852</spage><pages>e1004852-</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Contactins and Contactin-Associated Proteins, and Contactin-Associated Protein-Like 2 (CNTNAP2) in particular, have been widely cited as autism risk genes based on findings from homozygosity mapping, molecular cytogenetics, copy number variation analyses, and both common and rare single nucleotide association studies. However, data specifically with regard to the contribution of heterozygous single nucleotide variants (SNVs) have been inconsistent. In an effort to clarify the role of rare point mutations in CNTNAP2 and related gene families, we have conducted targeted next-generation sequencing and evaluated existing sequence data in cohorts totaling 2704 cases and 2747 controls. We find no evidence for statistically significant association of rare heterozygous mutations in any of the CNTN or CNTNAP genes, including CNTNAP2, placing marked limits on the scale of their plausible contribution to risk.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25621974</pmid><doi>10.1371/journal.pgen.1004852</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7404 |
| ispartof | PLoS genetics, 2015-01, Vol.11 (1), p.e1004852 |
| issn | 1553-7404 1553-7390 1553-7404 |
| language | eng |
| recordid | cdi_plos_journals_1685137702 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Public Library of Science (PLoS) |
| subjects | Autism Autistic Disorder - genetics Autistic Disorder - pathology Codon, Nonsense Contactins - genetics DNA Copy Number Variations Gene expression Gene mutation Genes Genetic aspects Genetic Association Studies Genetic Predisposition to Disease Humans Identification and classification Membrane Proteins - genetics Mutation Nerve Tissue Proteins - genetics Point Mutation Polymorphism, Single Nucleotide Sequence Analysis, DNA Sequence Deletion Studies |
| title | No evidence for association of autism with rare heterozygous point mutations in Contactin-Associated Protein-Like 2 (CNTNAP2), or in Other Contactin-Associated Proteins or Contactins |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T10%3A25%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=No%20evidence%20for%20association%20of%20autism%20with%20rare%20heterozygous%20point%20mutations%20in%20Contactin-Associated%20Protein-Like%202%20(CNTNAP2),%20or%20in%20Other%20Contactin-Associated%20Proteins%20or%20Contactins&rft.jtitle=PLoS%20genetics&rft.au=Murdoch,%20John%20D&rft.date=2015-01-01&rft.volume=11&rft.issue=1&rft.spage=e1004852&rft.pages=e1004852-&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1004852&rft_dat=%3Cgale_plos_%3EA418343218%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/25621974&rft_galeid=A418343218&rft_doaj_id=oai_doaj_org_article_032f22b95c454267af5fad02cfa2ee09&rfr_iscdi=true |