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Titolo:
Integrating expression-based drug response and SNP-based pharmacogenetic strategies into a single comprehensive pharmacogenomics program
Autore:
Rothberg, BEG; Ramesh, TM; Burgess, CE;
Indirizzi:
CuraGen Corp, New Haven, CT 06511 USA CuraGen Corp New Haven CT USA 06511CuraGen Corp, New Haven, CT 06511 USA
Titolo Testata:
DRUG DEVELOPMENT RESEARCH
fascicolo: 1, volume: 49, anno: 2000,
pagine: 54 - 64
SICI:
0272-4391(200001)49:1<54:IEDRAS>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENE-EXPRESSION; HEART-DISEASE; MESSENGER-RNA; FENFLURAMINE-PHENTERMINE; RECEPTOR SUPERFAMILY; DNA MICROARRAY; FATTY-ACIDS; HYBRIDIZATION; MIBEFRADIL; ACTIVATION;
Keywords:
pharmacogenomics; differential gene expression; single nucleotide polymorphisms;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Rothberg, BEG CuraGen Corp, 555 Long Wharf Dr, New Haven, CT 06511 USA CuraGen Corp 555 Long Wharf Dr New Haven CT USA 06511 11 USA
Citazione:
B.E.G. Rothberg et al., "Integrating expression-based drug response and SNP-based pharmacogenetic strategies into a single comprehensive pharmacogenomics program", DRUG DEV R, 49(1), 2000, pp. 54-64

Abstract

In the third millennium, competitive advantage in drug development will derive from expertise in two areas: 1) the ability to prioritize and triage hits from a combinatorial chemistry/high-throughput screening experiment andpursue only those hits most likely to succeed through clinical development, and 2) the ability to identify those patients capable of mounting a therapeutic response with minimal toxic effects. Pharmacogenomics, the branch ofgenomics addressing molecular pharmacology and toxicology, is anticipated to streamline drug development by addressing these issues. Pharmacogenomicsincludes two separate disciplines: expression pharmacogenomics and pharmacogenetics. Typically they are regarded as unique fields and are pursued independently from each ether. Here, we describe a pharmacogenomic strategy that combines and integrates both fields to create a single robust program. GeneCalling, a rapid, comprehensive differential transcript expression profiling technique, is applied to rodent models of drug response to identify novel markers predictive of drug efficacy and toxicity. SeqCalling, a high-throughput transcript sequencing strategy with a coding region bias, has identified 120,000 novel human single nucleotide polymorphisms (SNPs). Novel pharmacogenetic candidates are then identified by searching the human orthologs of rodent drug response genes for SeqCalling SNPs that can be pursued insystematic genotype screens to verify clinical correlations. In this manner, GeneCalling expression pharmacogenomics identifies markers capable of triaging reads from hits and SeqCalling converts a subset of these markers into pharmacogenetic correlates capable of identifying appropriately responsive patients. (C) 2000 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 01:09:35