Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1
We previously identified loci in the mouse genome that substantially influence the metastatic efficiency of mammary tumors. Here, we present data supporting the idea that the signal transduction molecule, Sipa1 , is a candidate for underlying the metastasis efficiency modifier locus Mtes1 . Analysis...
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| Veröffentlicht in: | Nature genetics 2005-10, Vol.37 (10), p.1055-1062 |
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| creator | Hunter, Kent W Park, Yeong-Gwan Zhao, Xiaohong Lesueur, Fabienne Lowy, Douglas R Lancaster, Mindy Pharoah, Paul Qian, Xiaolan |
| description | We previously identified loci in the mouse genome that substantially influence the metastatic efficiency of mammary tumors. Here, we present data supporting the idea that the signal transduction molecule,
Sipa1
, is a candidate for underlying the metastasis efficiency modifier locus
Mtes1
. Analysis of candidate genes identified a nonsynonymous amino acid polymorphism in Sipa1 that affects the Sipa1 Rap-GAP function. Spontaneous metastasis assays using cells ectopically expressing
Sipa1
or cells with knocked-down
Sipa1
expression showed that metastatic capacity was correlated with cellular
Sipa1
levels. We examined human expression data and found that they were consistent with the idea that
Sipa1
concentration has a role in metastasis. Taken together, these data suggest that the
Sipa1
polymorphism is one of the genetic polymorphisms underlying the
Mtes1
locus. This report is also the first demonstration, to our knowledge, of a constitutional genetic polymorphism affecting tumor metastasis. |
| doi_str_mv | 10.1038/ng1635 |
| format | Article |
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Sipa1
, is a candidate for underlying the metastasis efficiency modifier locus
Mtes1
. Analysis of candidate genes identified a nonsynonymous amino acid polymorphism in Sipa1 that affects the Sipa1 Rap-GAP function. Spontaneous metastasis assays using cells ectopically expressing
Sipa1
or cells with knocked-down
Sipa1
expression showed that metastatic capacity was correlated with cellular
Sipa1
levels. We examined human expression data and found that they were consistent with the idea that
Sipa1
concentration has a role in metastasis. Taken together, these data suggest that the
Sipa1
polymorphism is one of the genetic polymorphisms underlying the
Mtes1
locus. This report is also the first demonstration, to our knowledge, of a constitutional genetic polymorphism affecting tumor metastasis.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng1635</identifier><identifier>PMID: 16142231</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Amino acids ; Animal Genetics and Genomics ; Animals ; Biological Assay ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cell Adhesion - genetics ; Cercopithecus aethiops ; COS Cells ; Development and progression ; Diagnosis ; Gene expression ; Gene Function ; Genetic screening ; GTPase-Activating Proteins - genetics ; GTPase-Activating Proteins - metabolism ; Health aspects ; Human Genetics ; Humans ; Metastasis ; Methods ; Mice ; Mutation ; Neoplasm Metastasis - genetics ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Physiological aspects ; Polymorphism, Genetic ; rap GTP-Binding Proteins - genetics ; rap GTP-Binding Proteins - metabolism ; RNA, Small Interfering - genetics ; Transcriptional Activation ; Tumors</subject><ispartof>Nature genetics, 2005-10, Vol.37 (10), p.1055-1062</ispartof><rights>Springer Nature America, Inc. 2005</rights><rights>COPYRIGHT 2005 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-1cabd656836a357d300f7f4a96ae9796a8abd0bac8a78822635a85c308518fa53</citedby><cites>FETCH-LOGICAL-c555t-1cabd656836a357d300f7f4a96ae9796a8abd0bac8a78822635a85c308518fa53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng1635$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng1635$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27915,27916,41479,42548,51310</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16142231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hunter, Kent W</creatorcontrib><creatorcontrib>Park, Yeong-Gwan</creatorcontrib><creatorcontrib>Zhao, Xiaohong</creatorcontrib><creatorcontrib>Lesueur, Fabienne</creatorcontrib><creatorcontrib>Lowy, Douglas R</creatorcontrib><creatorcontrib>Lancaster, Mindy</creatorcontrib><creatorcontrib>Pharoah, Paul</creatorcontrib><creatorcontrib>Qian, Xiaolan</creatorcontrib><title>Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>We previously identified loci in the mouse genome that substantially influence the metastatic efficiency of mammary tumors. Here, we present data supporting the idea that the signal transduction molecule,
Sipa1
, is a candidate for underlying the metastasis efficiency modifier locus
Mtes1
. Analysis of candidate genes identified a nonsynonymous amino acid polymorphism in Sipa1 that affects the Sipa1 Rap-GAP function. Spontaneous metastasis assays using cells ectopically expressing
Sipa1
or cells with knocked-down
Sipa1
expression showed that metastatic capacity was correlated with cellular
Sipa1
levels. We examined human expression data and found that they were consistent with the idea that
Sipa1
concentration has a role in metastasis. Taken together, these data suggest that the
Sipa1
polymorphism is one of the genetic polymorphisms underlying the
Mtes1
locus. This report is also the first demonstration, to our knowledge, of a constitutional genetic polymorphism affecting tumor metastasis.</description><subject>Agriculture</subject><subject>Amino acids</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Biological Assay</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell Adhesion - genetics</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Gene expression</subject><subject>Gene Function</subject><subject>Genetic screening</subject><subject>GTPase-Activating Proteins - genetics</subject><subject>GTPase-Activating Proteins - metabolism</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Mice</subject><subject>Mutation</subject><subject>Neoplasm Metastasis - genetics</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Physiological aspects</subject><subject>Polymorphism, Genetic</subject><subject>rap GTP-Binding Proteins - genetics</subject><subject>rap GTP-Binding Proteins - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>Transcriptional Activation</subject><subject>Tumors</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkm9r1TAUxosobk79BCJBQfFFZ07TpOnLMfwzmAw29W3ITU9qRptekxS8395cWhxXBSUhCTm_85AnPEXxFOgpUCbf-h4E4_eKY-C1KKEBeT-fqYCypkwcFY9ivKUU6prKh8URCKirisFxcX3jthqIi0QTo33nOp2Q2CmQ2XcYhp3zPUnfkIyYdMwzk2itMw692ZFx6px1GMgwmTmSTwkjPC4eWD1EfLLuJ8WX9-8-n38sL68-XJyfXZaGc55KMHrTCS4kE5rxpmOU2sbWuhUa2yavMtfpRhupGymrKtvTkhtGJQdpNWcnxatFdxum7zPGpEYXDQ6D9jjNUQkp6gZa-k8QGto0Qu4VX_wG3k5z8NmEqvIDRFvJNkMvF6jXAyrn7ZSCNntFdQaS1QC0FZk6_QuVR4ejM5NH6_L9QcObg4bMJPyRej3HqC5urv-fvfp6yK7mTZhiDGjVNrhRh50CqvbRUUt0Mvh8NT9vRuzusDUrGXi9ADGXfI_h7nf-kHq2kF6nOeAvqbX8E8UYz88</recordid><startdate>20051001</startdate><enddate>20051001</enddate><creator>Hunter, Kent W</creator><creator>Park, Yeong-Gwan</creator><creator>Zhao, Xiaohong</creator><creator>Lesueur, Fabienne</creator><creator>Lowy, Douglas R</creator><creator>Lancaster, Mindy</creator><creator>Pharoah, Paul</creator><creator>Qian, Xiaolan</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20051001</creationdate><title>Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1</title><author>Hunter, Kent W ; Park, Yeong-Gwan ; Zhao, Xiaohong ; Lesueur, Fabienne ; Lowy, Douglas R ; Lancaster, Mindy ; Pharoah, Paul ; Qian, Xiaolan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c555t-1cabd656836a357d300f7f4a96ae9796a8abd0bac8a78822635a85c308518fa53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Agriculture</topic><topic>Amino acids</topic><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Biological Assay</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cell Adhesion - genetics</topic><topic>Cercopithecus aethiops</topic><topic>COS Cells</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Gene expression</topic><topic>Gene Function</topic><topic>Genetic screening</topic><topic>GTPase-Activating Proteins - genetics</topic><topic>GTPase-Activating Proteins - metabolism</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Metastasis</topic><topic>Methods</topic><topic>Mice</topic><topic>Mutation</topic><topic>Neoplasm Metastasis - genetics</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Physiological aspects</topic><topic>Polymorphism, Genetic</topic><topic>rap GTP-Binding Proteins - genetics</topic><topic>rap GTP-Binding Proteins - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>Transcriptional Activation</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hunter, Kent W</creatorcontrib><creatorcontrib>Park, Yeong-Gwan</creatorcontrib><creatorcontrib>Zhao, Xiaohong</creatorcontrib><creatorcontrib>Lesueur, Fabienne</creatorcontrib><creatorcontrib>Lowy, Douglas R</creatorcontrib><creatorcontrib>Lancaster, Mindy</creatorcontrib><creatorcontrib>Pharoah, Paul</creatorcontrib><creatorcontrib>Qian, Xiaolan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hunter, Kent W</au><au>Park, Yeong-Gwan</au><au>Zhao, Xiaohong</au><au>Lesueur, Fabienne</au><au>Lowy, Douglas R</au><au>Lancaster, Mindy</au><au>Pharoah, Paul</au><au>Qian, Xiaolan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2005-10-01</date><risdate>2005</risdate><volume>37</volume><issue>10</issue><spage>1055</spage><epage>1062</epage><pages>1055-1062</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><abstract>We previously identified loci in the mouse genome that substantially influence the metastatic efficiency of mammary tumors. Here, we present data supporting the idea that the signal transduction molecule,
Sipa1
, is a candidate for underlying the metastasis efficiency modifier locus
Mtes1
. Analysis of candidate genes identified a nonsynonymous amino acid polymorphism in Sipa1 that affects the Sipa1 Rap-GAP function. Spontaneous metastasis assays using cells ectopically expressing
Sipa1
or cells with knocked-down
Sipa1
expression showed that metastatic capacity was correlated with cellular
Sipa1
levels. We examined human expression data and found that they were consistent with the idea that
Sipa1
concentration has a role in metastasis. Taken together, these data suggest that the
Sipa1
polymorphism is one of the genetic polymorphisms underlying the
Mtes1
locus. This report is also the first demonstration, to our knowledge, of a constitutional genetic polymorphism affecting tumor metastasis.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>16142231</pmid><doi>10.1038/ng1635</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Agriculture Amino acids Animal Genetics and Genomics Animals Biological Assay Biomedical and Life Sciences Biomedicine Cancer Research Cell Adhesion - genetics Cercopithecus aethiops COS Cells Development and progression Diagnosis Gene expression Gene Function Genetic screening GTPase-Activating Proteins - genetics GTPase-Activating Proteins - metabolism Health aspects Human Genetics Humans Metastasis Methods Mice Mutation Neoplasm Metastasis - genetics Nuclear Proteins - genetics Nuclear Proteins - metabolism Physiological aspects Polymorphism, Genetic rap GTP-Binding Proteins - genetics rap GTP-Binding Proteins - metabolism RNA, Small Interfering - genetics Transcriptional Activation Tumors |
| title | Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1 |
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