Alterations of the hprt gene in human in vivo-derived 6-thioguanine-resistant T lymphocytes
Investigations into the extent and significance of somatic gene mutations occurring in vivo in humans have been hampered by the lack of a means of unambiguously defining the mutational origin of in vivo -derived variant cells. Several years ago we proposed that 6-thioguanine-resistant T lymphocytes,...
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| Veröffentlicht in: | Nature (London) 1985-07, Vol.316 (6026), p.369-371 |
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| creator | Albertini, Richard J. O'Neill, J. Patrick Nicklas, Janice A. Heintz, Nicholas H. Kelleher, Philip C. |
| description | Investigations into the extent and significance of somatic gene mutations occurring
in vivo
in humans have been hampered by the lack of a means of unambiguously defining the mutational origin of
in vivo
-derived variant cells. Several years ago we proposed that 6-thioguanine-resistant T lymphocytes, present at low frequencies in human peripheral blood, might be useful markers of
in vivo
somatic mutation
1,2
. We and others have since described methods for the isolation and study of these unusual cells
3–5
. The thioguanine-resistant T cells stably lack hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity, suggesting that they are somatic equivalents in normal individuals to cells from individuals with the X-chromosomal
hprt
Lesch-Nyhan germinal mutation
6,7
. We now report that
in vivo
-derived thioguanine-resistant T-cell colonies from a single normal individual show a variety of
hprt
structural alterations, as determined by Southern blot analysis. This finding demonstrates unequivocally that these cells are genetic mutants and validates their use for fundamental and applied mutational studies in humans. |
| doi_str_mv | 10.1038/316369a0 |
| format | Article |
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in vivo
in humans have been hampered by the lack of a means of unambiguously defining the mutational origin of
in vivo
-derived variant cells. Several years ago we proposed that 6-thioguanine-resistant T lymphocytes, present at low frequencies in human peripheral blood, might be useful markers of
in vivo
somatic mutation
1,2
. We and others have since described methods for the isolation and study of these unusual cells
3–5
. The thioguanine-resistant T cells stably lack hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity, suggesting that they are somatic equivalents in normal individuals to cells from individuals with the X-chromosomal
hprt
Lesch-Nyhan germinal mutation
6,7
. We now report that
in vivo
-derived thioguanine-resistant T-cell colonies from a single normal individual show a variety of
hprt
structural alterations, as determined by Southern blot analysis. This finding demonstrates unequivocally that these cells are genetic mutants and validates their use for fundamental and applied mutational studies in humans.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/316369a0</identifier><identifier>PMID: 2991767</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Biological and medical sciences ; Classical genetics, quantitative genetics, hybrids ; Clone Cells - enzymology ; DNA - analysis ; DNA Restriction Enzymes ; Drug Resistance ; Fundamental and applied biological sciences. Psychology ; Genetics of eukaryotes. Biological and molecular evolution ; Human ; Humanities and Social Sciences ; Humans ; Hypoxanthine Phosphoribosyltransferase - genetics ; letter ; Male ; multidisciplinary ; Mutation ; Phenotype ; Science ; Science (multidisciplinary) ; T-Lymphocytes - drug effects ; T-Lymphocytes - enzymology ; Thioguanine - pharmacology</subject><ispartof>Nature (London), 1985-07, Vol.316 (6026), p.369-371</ispartof><rights>Springer Nature Limited 1985</rights><rights>1985 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2870-15a8b140fb9e17c9779afb9f0f5ced8961daf7e32b4401a9771847a3570e8cb03</citedby><cites>FETCH-LOGICAL-c2870-15a8b140fb9e17c9779afb9f0f5ced8961daf7e32b4401a9771847a3570e8cb03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/316369a0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/316369a0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=9212357$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2991767$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Albertini, Richard J.</creatorcontrib><creatorcontrib>O'Neill, J. Patrick</creatorcontrib><creatorcontrib>Nicklas, Janice A.</creatorcontrib><creatorcontrib>Heintz, Nicholas H.</creatorcontrib><creatorcontrib>Kelleher, Philip C.</creatorcontrib><title>Alterations of the hprt gene in human in vivo-derived 6-thioguanine-resistant T lymphocytes</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Investigations into the extent and significance of somatic gene mutations occurring
in vivo
in humans have been hampered by the lack of a means of unambiguously defining the mutational origin of
in vivo
-derived variant cells. Several years ago we proposed that 6-thioguanine-resistant T lymphocytes, present at low frequencies in human peripheral blood, might be useful markers of
in vivo
somatic mutation
1,2
. We and others have since described methods for the isolation and study of these unusual cells
3–5
. The thioguanine-resistant T cells stably lack hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity, suggesting that they are somatic equivalents in normal individuals to cells from individuals with the X-chromosomal
hprt
Lesch-Nyhan germinal mutation
6,7
. We now report that
in vivo
-derived thioguanine-resistant T-cell colonies from a single normal individual show a variety of
hprt
structural alterations, as determined by Southern blot analysis. This finding demonstrates unequivocally that these cells are genetic mutants and validates their use for fundamental and applied mutational studies in humans.</description><subject>Biological and medical sciences</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Clone Cells - enzymology</subject><subject>DNA - analysis</subject><subject>DNA Restriction Enzymes</subject><subject>Drug Resistance</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Human</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hypoxanthine Phosphoribosyltransferase - genetics</subject><subject>letter</subject><subject>Male</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Phenotype</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - enzymology</subject><subject>Thioguanine - pharmacology</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE2LFDEQhoMo6-wq-AeEHETWQ2uqk8nHcVn8ggUv68lDk05XT2fpTsYkPTD_3iwz7sWDpyp4H96iHkLeAPsIjOtPHCSXxrJnZANCyUZIrZ6TDWOtbpjm8iW5zPmBMbYFJS7IRWsMKKk25NfNXDDZ4mPINI60TEinfSp0hwGpD3RaFxsel4M_xGbA5A84UNmUycfdaoMP2CTMPhcbCr2n83HZT9EdC-ZX5MVo54yvz_OK_Pzy-f72W3P34-v325u7xrVasQa2Vvcg2NgbBOWMUsbWfWTj1uGgjYTBjgp52wvBwNYctFCWbxVD7XrGr8j7U-8-xd8r5tItPjucZxswrrlTsuUCjPovCAK0FIZX8PoEuhRzTjh2--QXm44dsO5RePdXeEXfnjvXfsHhCTwbrvm7c26zs_OYbHA-P2GmhbZ-UrEPJyzXJOwwdQ9xTaFq-_fkH4aGlF8</recordid><startdate>19850725</startdate><enddate>19850725</enddate><creator>Albertini, Richard J.</creator><creator>O'Neill, J. Patrick</creator><creator>Nicklas, Janice A.</creator><creator>Heintz, Nicholas H.</creator><creator>Kelleher, Philip C.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><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>7T5</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19850725</creationdate><title>Alterations of the hprt gene in human in vivo-derived 6-thioguanine-resistant T lymphocytes</title><author>Albertini, Richard J. ; O'Neill, J. Patrick ; Nicklas, Janice A. ; Heintz, Nicholas H. ; Kelleher, Philip C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2870-15a8b140fb9e17c9779afb9f0f5ced8961daf7e32b4401a9771847a3570e8cb03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Biological and medical sciences</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Clone Cells - enzymology</topic><topic>DNA - analysis</topic><topic>DNA Restriction Enzymes</topic><topic>Drug Resistance</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Human</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hypoxanthine Phosphoribosyltransferase - genetics</topic><topic>letter</topic><topic>Male</topic><topic>multidisciplinary</topic><topic>Mutation</topic><topic>Phenotype</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - enzymology</topic><topic>Thioguanine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Albertini, Richard J.</creatorcontrib><creatorcontrib>O'Neill, J. Patrick</creatorcontrib><creatorcontrib>Nicklas, Janice A.</creatorcontrib><creatorcontrib>Heintz, Nicholas H.</creatorcontrib><creatorcontrib>Kelleher, Philip C.</creatorcontrib><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>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Albertini, Richard J.</au><au>O'Neill, J. Patrick</au><au>Nicklas, Janice A.</au><au>Heintz, Nicholas H.</au><au>Kelleher, Philip C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alterations of the hprt gene in human in vivo-derived 6-thioguanine-resistant T lymphocytes</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>1985-07-25</date><risdate>1985</risdate><volume>316</volume><issue>6026</issue><spage>369</spage><epage>371</epage><pages>369-371</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>Investigations into the extent and significance of somatic gene mutations occurring
in vivo
in humans have been hampered by the lack of a means of unambiguously defining the mutational origin of
in vivo
-derived variant cells. Several years ago we proposed that 6-thioguanine-resistant T lymphocytes, present at low frequencies in human peripheral blood, might be useful markers of
in vivo
somatic mutation
1,2
. We and others have since described methods for the isolation and study of these unusual cells
3–5
. The thioguanine-resistant T cells stably lack hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity, suggesting that they are somatic equivalents in normal individuals to cells from individuals with the X-chromosomal
hprt
Lesch-Nyhan germinal mutation
6,7
. We now report that
in vivo
-derived thioguanine-resistant T-cell colonies from a single normal individual show a variety of
hprt
structural alterations, as determined by Southern blot analysis. This finding demonstrates unequivocally that these cells are genetic mutants and validates their use for fundamental and applied mutational studies in humans.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>2991767</pmid><doi>10.1038/316369a0</doi><tpages>3</tpages></addata></record> |
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| ispartof | Nature (London), 1985-07, Vol.316 (6026), p.369-371 |
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| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Biological and medical sciences Classical genetics, quantitative genetics, hybrids Clone Cells - enzymology DNA - analysis DNA Restriction Enzymes Drug Resistance Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Human Humanities and Social Sciences Humans Hypoxanthine Phosphoribosyltransferase - genetics letter Male multidisciplinary Mutation Phenotype Science Science (multidisciplinary) T-Lymphocytes - drug effects T-Lymphocytes - enzymology Thioguanine - pharmacology |
| title | Alterations of the hprt gene in human in vivo-derived 6-thioguanine-resistant T lymphocytes |
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