Detection of Functional Single-Nucleotide Polymorphisms That Affect Apoptosis
Human EBV-transformed B lymphocyte cell lines (LCLs) were used to measure the apoptotic response of individuals to γ radiation. The responses form a normal distribution around a median of 35.5% apoptosis with a range of 12-58%. This heterogeneous response has a genetic basis. LCLs from Caucasian don...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2005-11, Vol.102 (45), p.16297-16302 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Harris, Sandra L. German Gil Robins, Harlan Hu, Wenwei Kim Hirshfield Elisabeth Bond Gareth Bond Levine, Arnold J. |
| description | Human EBV-transformed B lymphocyte cell lines (LCLs) were used to measure the apoptotic response of individuals to γ radiation. The responses form a normal distribution around a median of 35.5% apoptosis with a range of 12-58%. This heterogeneous response has a genetic basis. LCLs from Caucasian donors and African American donors form distinct distributions of apoptotic response; all of the 11 LCLs comprising the lowest responding group (exhibiting between 12-20% apoptosis) are from Caucasian donors. The assay is capable of detecting significant effects of SNPs in two genes, MDM2 and AKT1, whose products are involved in controlling the p53 pathway and cellular response to DNA damage, suggesting that these data and this assay can be used to identify novel SNPs in other genes whose products impact the cellular response to radiation. Finally, the LCLs in the lowest apoptotic response group have the highest concentration of AKT1 protein and all harbor a haplotype in AKT1 that is present in Caucasians but absent in African Americans. |
| doi_str_mv | 10.1073/pnas.0508390102 |
| format | Article |
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The responses form a normal distribution around a median of 35.5% apoptosis with a range of 12-58%. This heterogeneous response has a genetic basis. LCLs from Caucasian donors and African American donors form distinct distributions of apoptotic response; all of the 11 LCLs comprising the lowest responding group (exhibiting between 12-20% apoptosis) are from Caucasian donors. The assay is capable of detecting significant effects of SNPs in two genes, MDM2 and AKT1, whose products are involved in controlling the p53 pathway and cellular response to DNA damage, suggesting that these data and this assay can be used to identify novel SNPs in other genes whose products impact the cellular response to radiation. Finally, the LCLs in the lowest apoptotic response group have the highest concentration of AKT1 protein and all harbor a haplotype in AKT1 that is present in Caucasians but absent in African Americans.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0508390102</identifier><identifier>PMID: 16260726</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>African Americans ; Alleles ; Apoptosis ; B lymphocytes ; B-Lymphocytes - metabolism ; B-Lymphocytes - radiation effects ; Biological Sciences ; Cell Line, Transformed ; Cell lines ; Gamma rays ; Genetics ; Haplotypes ; Humans ; Irradiation ; Normal distribution ; Polymorphism ; Polymorphism, Single Nucleotide ; Proteins ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-mdm2 - genetics ; Small interfering RNA ; Transfection ; Tumor Suppressor Protein p53 - physiology ; White people</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2005-11, Vol.102 (45), p.16297-16302</ispartof><rights>Copyright 2005 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 8, 2005</rights><rights>Copyright © 2005, The National Academy of Sciences 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-54e91ff833783e15957bce093bd17ee9aceadd6615aba5b157a6e90bb510e3703</citedby><cites>FETCH-LOGICAL-c529t-54e91ff833783e15957bce093bd17ee9aceadd6615aba5b157a6e90bb510e3703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/102/45.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/4152420$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/4152420$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27923,27924,53790,53792,58016,58249</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16260726$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harris, Sandra L.</creatorcontrib><creatorcontrib>German Gil</creatorcontrib><creatorcontrib>Robins, Harlan</creatorcontrib><creatorcontrib>Hu, Wenwei</creatorcontrib><creatorcontrib>Kim Hirshfield</creatorcontrib><creatorcontrib>Elisabeth Bond</creatorcontrib><creatorcontrib>Gareth Bond</creatorcontrib><creatorcontrib>Levine, Arnold J.</creatorcontrib><title>Detection of Functional Single-Nucleotide Polymorphisms That Affect Apoptosis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Human EBV-transformed B lymphocyte cell lines (LCLs) were used to measure the apoptotic response of individuals to γ radiation. The responses form a normal distribution around a median of 35.5% apoptosis with a range of 12-58%. This heterogeneous response has a genetic basis. LCLs from Caucasian donors and African American donors form distinct distributions of apoptotic response; all of the 11 LCLs comprising the lowest responding group (exhibiting between 12-20% apoptosis) are from Caucasian donors. The assay is capable of detecting significant effects of SNPs in two genes, MDM2 and AKT1, whose products are involved in controlling the p53 pathway and cellular response to DNA damage, suggesting that these data and this assay can be used to identify novel SNPs in other genes whose products impact the cellular response to radiation. Finally, the LCLs in the lowest apoptotic response group have the highest concentration of AKT1 protein and all harbor a haplotype in AKT1 that is present in Caucasians but absent in African Americans.</description><subject>African Americans</subject><subject>Alleles</subject><subject>Apoptosis</subject><subject>B lymphocytes</subject><subject>B-Lymphocytes - metabolism</subject><subject>B-Lymphocytes - radiation effects</subject><subject>Biological Sciences</subject><subject>Cell Line, Transformed</subject><subject>Cell lines</subject><subject>Gamma rays</subject><subject>Genetics</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Irradiation</subject><subject>Normal distribution</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-mdm2 - genetics</subject><subject>Small interfering RNA</subject><subject>Transfection</subject><subject>Tumor Suppressor Protein p53 - physiology</subject><subject>White people</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0c1rFDEYBvAgil2rZy8ig4eCh2nffE8uwtJaFeoHWM8hM_NOd5bsZDrJiP3vzbpLV730lEB-70OSh5CXFE4paH42Di6egoSKG6DAHpEFBUNLJQw8JgsApstKMHFEnsW4BgAjK3hKjqhiCjRTC_L5AhM2qQ9DEbrich7-7J0vvvfDjcfyy9x4DKlvsfgW_N0mTOOqj5tYXK9cKpZdl4eL5RjGFGIfn5MnnfMRX-zXY_Lj8v31-cfy6uuHT-fLq7KRzKRSCjS06yrOdcWRSiN13SAYXrdUIxrXoGtbpah0tZM1ldopNFDXkgJyDfyYvNvljnO9wbbBIU3O23HqN266s8H19t-ToV_Zm_DTUlZxoXkOONkHTOF2xpjspo8Neu8GDHO0qtJaVAwehNRwrYSiGb75D67DPOWfjJYB5VLmTjI626FmCjFO2N1fmYLdFmq3hdpDoXni9d8vPfh9gxkUe7CdPMQxK-RWGZ3J2weI7WbvE_5K2b7a2XVMYbrHgkom8nf8BvHBvxM</recordid><startdate>20051108</startdate><enddate>20051108</enddate><creator>Harris, Sandra L.</creator><creator>German Gil</creator><creator>Robins, Harlan</creator><creator>Hu, Wenwei</creator><creator>Kim Hirshfield</creator><creator>Elisabeth Bond</creator><creator>Gareth Bond</creator><creator>Levine, Arnold J.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20051108</creationdate><title>Detection of Functional Single-Nucleotide Polymorphisms That Affect Apoptosis</title><author>Harris, Sandra L. ; 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| subjects | African Americans Alleles Apoptosis B lymphocytes B-Lymphocytes - metabolism B-Lymphocytes - radiation effects Biological Sciences Cell Line, Transformed Cell lines Gamma rays Genetics Haplotypes Humans Irradiation Normal distribution Polymorphism Polymorphism, Single Nucleotide Proteins Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-mdm2 - genetics Small interfering RNA Transfection Tumor Suppressor Protein p53 - physiology White people |
| title | Detection of Functional Single-Nucleotide Polymorphisms That Affect Apoptosis |
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