Matches in SemOpenAlex for { <https://semopenalex.org/work/W2609314580> ?p ?o ?g. }
Showing items 1 to 72 of
72
with 100 items per page.
- W2609314580 endingPage "341" @default.
- W2609314580 startingPage "341" @default.
- W2609314580 abstract "1484 Risk of cancer is a complex function of exposures (external and endogenous) and genetic susceptibility to these exposures. For each exposure, the function of multiple pathways may be relevant. As pathways can have dozens of genes and most genes have multiple variant single nucleotide polymorphisms (SNPs), 100s of SNPs are candidate susceptibility factors. Discerning the variants that affect function and cancer susceptibility is a major challenge. The goal of this study was identification of polymorphisms in base excision repair (BER) and antioxidant (AO) genes that affect the amount of DNA damage in untreated cells, primarily damage from oxidative metabolism, and the ability to repair damage induced by exposure to ionizing radiation (IR). Using the alkaline Comet assay we quantified single strand breaks and abasic sites in untreated cells and in cells immediately and 15 minutes after exposure to 5Gy IR, in 80 lymphoblastoid cell lines of the DNA Polymorphism Discovery Resource (DPDR). Comet distributed moment was the parameter used to quantify damage. Genotypes of the cell lines, known from extensive resequencing studies of the DPDR, included 174 variants of 34 BER genes (159 amino acid substitution SNPs and 15 SNPs in upstream ∼150bp sequences) and 17 amino acid substitution SNPs of 5 AO genes. Random Forests Regression (RFR) was used to identify SNPs that were important for predicting 2 phenotypes: endogenous (background) damage and % damage repaired 15 min after IR. Using a stringent cutoff for importance, there were 5 SNPs from 4 genes that were most influential for background damage (from greatest impact to least, POLD1 Arg19His, XRCC1 Arg399Gln, XRCC1 Val72Ala, LIG3 Arg780His, RPA4 Ala33Thr) and 7 influential SNPs for repair of IR damage (RPA4 Ala33Thr, XRCC1 Val72Ala, MPG 5 prime UTR, PNKP Pro20Ser, RAD23B Ala249Val, POLE Phe695Ile, LPO Thr105Ile). It is notable that the frequencies of these important SNPs range from 0.01 to 0.42 and that the SIFT scores of these variants independently predict an impact on protein function. In summary, RFR efficiently identified 10 out of 191 polymorphisms that help predict two phenotypes relevant to cancer risk. This study demonstrates the ability to use heuristic machine learning techniques to identify functionally important genetic variation by analyzing relationships between phenotypes and complex genotypes. This work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48." @default.
- W2609314580 created "2017-05-05" @default.
- W2609314580 creator A5011924682 @default.
- W2609314580 creator A5022170183 @default.
- W2609314580 creator A5025875477 @default.
- W2609314580 creator A5065421475 @default.
- W2609314580 creator A5089386711 @default.
- W2609314580 date "2004-04-01" @default.
- W2609314580 modified "2023-09-26" @default.
- W2609314580 title "Orthogonal haplotype structure in 106 DNA repair and cell cycle control genes simplifies the search for gene-disease association" @default.
- W2609314580 hasPublicationYear "2004" @default.
- W2609314580 type Work @default.
- W2609314580 sameAs 2609314580 @default.
- W2609314580 citedByCount "0" @default.
- W2609314580 crossrefType "journal-article" @default.
- W2609314580 hasAuthorship W2609314580A5011924682 @default.
- W2609314580 hasAuthorship W2609314580A5022170183 @default.
- W2609314580 hasAuthorship W2609314580A5025875477 @default.
- W2609314580 hasAuthorship W2609314580A5065421475 @default.
- W2609314580 hasAuthorship W2609314580A5089386711 @default.
- W2609314580 hasConcept C104317684 @default.
- W2609314580 hasConcept C134935766 @default.
- W2609314580 hasConcept C135763542 @default.
- W2609314580 hasConcept C143425029 @default.
- W2609314580 hasConcept C153209595 @default.
- W2609314580 hasConcept C197754878 @default.
- W2609314580 hasConcept C2776999993 @default.
- W2609314580 hasConcept C2780358455 @default.
- W2609314580 hasConcept C54355233 @default.
- W2609314580 hasConcept C552990157 @default.
- W2609314580 hasConcept C86803240 @default.
- W2609314580 hasConceptScore W2609314580C104317684 @default.
- W2609314580 hasConceptScore W2609314580C134935766 @default.
- W2609314580 hasConceptScore W2609314580C135763542 @default.
- W2609314580 hasConceptScore W2609314580C143425029 @default.
- W2609314580 hasConceptScore W2609314580C153209595 @default.
- W2609314580 hasConceptScore W2609314580C197754878 @default.
- W2609314580 hasConceptScore W2609314580C2776999993 @default.
- W2609314580 hasConceptScore W2609314580C2780358455 @default.
- W2609314580 hasConceptScore W2609314580C54355233 @default.
- W2609314580 hasConceptScore W2609314580C552990157 @default.
- W2609314580 hasConceptScore W2609314580C86803240 @default.
- W2609314580 hasLocation W26093145801 @default.
- W2609314580 hasOpenAccess W2609314580 @default.
- W2609314580 hasPrimaryLocation W26093145801 @default.
- W2609314580 hasRelatedWork W1524974137 @default.
- W2609314580 hasRelatedWork W1534418196 @default.
- W2609314580 hasRelatedWork W1831672189 @default.
- W2609314580 hasRelatedWork W2052961175 @default.
- W2609314580 hasRelatedWork W2094367451 @default.
- W2609314580 hasRelatedWork W2099609898 @default.
- W2609314580 hasRelatedWork W2105974859 @default.
- W2609314580 hasRelatedWork W2110807665 @default.
- W2609314580 hasRelatedWork W2132190547 @default.
- W2609314580 hasRelatedWork W2135525122 @default.
- W2609314580 hasRelatedWork W2151463929 @default.
- W2609314580 hasRelatedWork W2286698897 @default.
- W2609314580 hasRelatedWork W2289946584 @default.
- W2609314580 hasRelatedWork W2462592384 @default.
- W2609314580 hasRelatedWork W2562959903 @default.
- W2609314580 hasRelatedWork W2593683010 @default.
- W2609314580 hasRelatedWork W2950287006 @default.
- W2609314580 hasRelatedWork W2964670430 @default.
- W2609314580 hasRelatedWork W3029536894 @default.
- W2609314580 hasRelatedWork W2747310987 @default.
- W2609314580 hasVolume "64" @default.
- W2609314580 isParatext "false" @default.
- W2609314580 isRetracted "false" @default.
- W2609314580 magId "2609314580" @default.
- W2609314580 workType "article" @default.