Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR
Genetic association studies provide considerable evidence that the 10‐repeat allele of a variable number tandem repeat (VNTR) in the 3′‐untranslated region (3′‐UTR) of the dopamine transporter gene (DAT1) is associated with a range of psychiatric phenotypes, most notably, attention deficit hyperacti...
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Veröffentlicht in: | American journal of medical genetics 2002-12, Vol.114 (8), p.975-979 |
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description | Genetic association studies provide considerable evidence that the 10‐repeat allele of a variable number tandem repeat (VNTR) in the 3′‐untranslated region (3′‐UTR) of the dopamine transporter gene (DAT1) is associated with a range of psychiatric phenotypes, most notably, attention deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study, we measured DAT1 messenger RNA levels in cerebellum, temporal lobe, and lymphocytes using quantitative real‐time reverse‐transcription polymerase chain reaction. Relative to a set of four control housekeeping genes (β‐actin, GAPD, ribosomal 18S, and β2‐microglobulin) we observed that increased levels of DAT1 expression were associated with the number of 10‐repeat alleles. These data provide direct evidence that the VNTR, or another polymorphism in linkage disequilibrium with the VNTR, is involved in regulating expression of this gene. © 2002 Wiley‐Liss, Inc. |
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The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study, we measured DAT1 messenger RNA levels in cerebellum, temporal lobe, and lymphocytes using quantitative real‐time reverse‐transcription polymerase chain reaction. Relative to a set of four control housekeeping genes (β‐actin, GAPD, ribosomal 18S, and β2‐microglobulin) we observed that increased levels of DAT1 expression were associated with the number of 10‐repeat alleles. These data provide direct evidence that the VNTR, or another polymorphism in linkage disequilibrium with the VNTR, is involved in regulating expression of this gene. © 2002 Wiley‐Liss, Inc.</description><identifier>ISSN: 0148-7299</identifier><identifier>EISSN: 1096-8628</identifier><identifier>DOI: 10.1002/ajmg.b.10948</identifier><identifier>PMID: 12457396</identifier><identifier>CODEN: AJMGDA</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>3' Untranslated Regions ; Attention Deficit Disorder with Hyperactivity - genetics ; attention deficit hyperactivity disorder ; Biological and medical sciences ; Brain - physiology ; Central nervous system ; Central neurotransmission. Neuromudulation. Pathways and receptors ; Dopamine Plasma Membrane Transport Proteins ; dopamine transporter gene (DAT1) ; expression ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation ; Humans ; Lymphocytes - physiology ; Membrane Glycoproteins ; Membrane Transport Proteins - genetics ; Minisatellite Repeats ; Nerve Tissue Proteins ; quantitative RT-PCR ; Reverse Transcriptase Polymerase Chain Reaction ; TaqMan ; Vertebrates: nervous system and sense organs ; VNTR</subject><ispartof>American journal of medical genetics, 2002-12, Vol.114 (8), p.975-979</ispartof><rights>Copyright © 2002 Wiley‐Liss, Inc.</rights><rights>2003 INIST-CNRS</rights><rights>Copyright 2002 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4658-d71d3bf264fee23c37edc3d5fda2b19e70c0f29fb9aa99aaec0a3b4c454d8dcc3</citedby><cites>FETCH-LOGICAL-c4658-d71d3bf264fee23c37edc3d5fda2b19e70c0f29fb9aa99aaec0a3b4c454d8dcc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14354121$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12457396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mill, Jonathan</creatorcontrib><creatorcontrib>Asherson, Philip</creatorcontrib><creatorcontrib>Browes, Clare</creatorcontrib><creatorcontrib>D'Souza, Ursula</creatorcontrib><creatorcontrib>Craig, Ian</creatorcontrib><title>Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR</title><title>American journal of medical genetics</title><addtitle>Am. J. Med. Genet</addtitle><description>Genetic association studies provide considerable evidence that the 10‐repeat allele of a variable number tandem repeat (VNTR) in the 3′‐untranslated region (3′‐UTR) of the dopamine transporter gene (DAT1) is associated with a range of psychiatric phenotypes, most notably, attention deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study, we measured DAT1 messenger RNA levels in cerebellum, temporal lobe, and lymphocytes using quantitative real‐time reverse‐transcription polymerase chain reaction. Relative to a set of four control housekeeping genes (β‐actin, GAPD, ribosomal 18S, and β2‐microglobulin) we observed that increased levels of DAT1 expression were associated with the number of 10‐repeat alleles. These data provide direct evidence that the VNTR, or another polymorphism in linkage disequilibrium with the VNTR, is involved in regulating expression of this gene. © 2002 Wiley‐Liss, Inc.</description><subject>3' Untranslated Regions</subject><subject>Attention Deficit Disorder with Hyperactivity - genetics</subject><subject>attention deficit hyperactivity disorder</subject><subject>Biological and medical sciences</subject><subject>Brain - physiology</subject><subject>Central nervous system</subject><subject>Central neurotransmission. Neuromudulation. Pathways and receptors</subject><subject>Dopamine Plasma Membrane Transport Proteins</subject><subject>dopamine transporter gene (DAT1)</subject><subject>expression</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Lymphocytes - physiology</subject><subject>Membrane Glycoproteins</subject><subject>Membrane Transport Proteins - genetics</subject><subject>Minisatellite Repeats</subject><subject>Nerve Tissue Proteins</subject><subject>quantitative RT-PCR</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>TaqMan</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>VNTR</subject><issn>0148-7299</issn><issn>1096-8628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EtuFDEQBmALgcgQ2LFG3sCKDn71i10YhiFRCFFrAoiN5barJ076Fbs7pHccIKfhSJwEJzOQHQurrNJXVdKP0HNK9igh7I06b9Z7ZfjnInuAZqEmUZaw7CGaESqyKGV5voOeeH9OCA0N9hjtUCbilOfJDN0srnsH3tuuxV2FhzPAputVY1vAg1Ot7zs3gMNrCA3rsYP1WKsBDC6nO81___yFT1cF_nK8Kt7ixZU10GrAlesaXDplW6xag-up6c86PQ3g8ehtu8aXo2oHO6jBXgEuVtHJvHiKHlWq9vBsW3fR6YfFav4xOvq8PJjvH0VaJHEWmZQaXlYsERUA45qnYDQ3cWUUK2kOKdGkYnlV5krl4YEmipdCi1iYzGjNd9Grzd7edZcj-EE21muoa9VCN3qZspSRnMYBvt5A7TrvHVSyd7ZRbpKUyNv05W36spR36Qf-Yrt3LBsw93gbdwAvt0B5reoqBKytv3eCx4IyGhzfuB-2hum_R-X-4afl3_PRZsr6Aa7_TSl3IZOUp7H8eryU35cFeXdy-E2-538AWjiw1w</recordid><startdate>20021208</startdate><enddate>20021208</enddate><creator>Mill, Jonathan</creator><creator>Asherson, Philip</creator><creator>Browes, Clare</creator><creator>D'Souza, Ursula</creator><creator>Craig, Ian</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20021208</creationdate><title>Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR</title><author>Mill, Jonathan ; Asherson, Philip ; Browes, Clare ; D'Souza, Ursula ; Craig, Ian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4658-d71d3bf264fee23c37edc3d5fda2b19e70c0f29fb9aa99aaec0a3b4c454d8dcc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>3' Untranslated Regions</topic><topic>Attention Deficit Disorder with Hyperactivity - genetics</topic><topic>attention deficit hyperactivity disorder</topic><topic>Biological and medical sciences</topic><topic>Brain - physiology</topic><topic>Central nervous system</topic><topic>Central neurotransmission. Neuromudulation. Pathways and receptors</topic><topic>Dopamine Plasma Membrane Transport Proteins</topic><topic>dopamine transporter gene (DAT1)</topic><topic>expression</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Lymphocytes - physiology</topic><topic>Membrane Glycoproteins</topic><topic>Membrane Transport Proteins - genetics</topic><topic>Minisatellite Repeats</topic><topic>Nerve Tissue Proteins</topic><topic>quantitative RT-PCR</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>TaqMan</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>VNTR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mill, Jonathan</creatorcontrib><creatorcontrib>Asherson, Philip</creatorcontrib><creatorcontrib>Browes, Clare</creatorcontrib><creatorcontrib>D'Souza, Ursula</creatorcontrib><creatorcontrib>Craig, Ian</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of medical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mill, Jonathan</au><au>Asherson, Philip</au><au>Browes, Clare</au><au>D'Souza, Ursula</au><au>Craig, Ian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR</atitle><jtitle>American journal of medical genetics</jtitle><addtitle>Am. J. Med. Genet</addtitle><date>2002-12-08</date><risdate>2002</risdate><volume>114</volume><issue>8</issue><spage>975</spage><epage>979</epage><pages>975-979</pages><issn>0148-7299</issn><eissn>1096-8628</eissn><coden>AJMGDA</coden><abstract>Genetic association studies provide considerable evidence that the 10‐repeat allele of a variable number tandem repeat (VNTR) in the 3′‐untranslated region (3′‐UTR) of the dopamine transporter gene (DAT1) is associated with a range of psychiatric phenotypes, most notably, attention deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study, we measured DAT1 messenger RNA levels in cerebellum, temporal lobe, and lymphocytes using quantitative real‐time reverse‐transcription polymerase chain reaction. Relative to a set of four control housekeeping genes (β‐actin, GAPD, ribosomal 18S, and β2‐microglobulin) we observed that increased levels of DAT1 expression were associated with the number of 10‐repeat alleles. These data provide direct evidence that the VNTR, or another polymorphism in linkage disequilibrium with the VNTR, is involved in regulating expression of this gene. © 2002 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>12457396</pmid><doi>10.1002/ajmg.b.10948</doi><tpages>5</tpages></addata></record> |
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subjects | 3' Untranslated Regions Attention Deficit Disorder with Hyperactivity - genetics attention deficit hyperactivity disorder Biological and medical sciences Brain - physiology Central nervous system Central neurotransmission. Neuromudulation. Pathways and receptors Dopamine Plasma Membrane Transport Proteins dopamine transporter gene (DAT1) expression Fundamental and applied biological sciences. Psychology Gene Expression Regulation Humans Lymphocytes - physiology Membrane Glycoproteins Membrane Transport Proteins - genetics Minisatellite Repeats Nerve Tissue Proteins quantitative RT-PCR Reverse Transcriptase Polymerase Chain Reaction TaqMan Vertebrates: nervous system and sense organs VNTR |
title | Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: Evidence from brain and lymphocytes using quantitative RT-PCR |
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