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  Genetic variation and pharmacogenomics : concepts, facts, and challenges

Hoehe, M. R., & Kroslak, T. (2004). Genetic variation and pharmacogenomics: concepts, facts, and challenges. Dialogues in Clinical Neuroscience, 6(1), 5-25.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8930-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-8931-A
Genre: Journal Article
Alternative Title : Dialogues Clin Neurosci

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 Creators:
Hoehe, Margret R.1, Author              
Kroslak, Thomas2, Author
Affiliations:
1Genetic Variation, Haplotypes, and Genetics of Complex Disease (Margret Hoehe), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479651              
2Max Planck Society, ou_persistent13              

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Free keywords: genetic variation; DNA sequence; candidate gene; single nucleotide polymorphism; haplotype; drug response
 Abstract: The analysis of genetic variation in candidate genes is an issue of central importance in pharmacogenomics. The spe- cific approaches taken will have a critical impact on the successful identification of disease genes, the molecular cor- relates of drug response, and the establishment of meaningful relationships between genetic variants and phenotypes of biomedical and pharmaceutical importance in general. Against a historical background, this article distinguishes different approaches to candidate gene analysis, reflecting different stages in human genome research. Only recently has it become feasible to analyze genetic variation systematically at the ultimate level of resolution, ie, the DNA sequence. In this context, the importance of haplotype-based approaches to candidate gene analysis has at last been recognized; the determination of the specific combinations of variants for each of the two sequences of a gene defined as a haplotype is essential. An up-to-date summary of such maximum resolution data on the amount, nature, and struc- ture of genetic variation in candidate genes will be given. These data demonstrate abundant gene sequence and hap- lotype diversity. Numerous individually different forms of a gene may exist. This presents major challenges to the analy- sis of relationships between genetic variation, gene function, and phenotype. First solutions seem within reach. The implications of naturally occurring variation for pharmacogenomics and “personalized” medicine are now evident. Future approaches to the identification, evaluation, and prioritization of drug targets, the optimization of clinical tri- als, and the development of efficient therapies must be based on in-depth knowledge of candidate gene variation as an essential prerequisite.

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Language(s): eng - English
 Dates: 2004
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 230220
 Degree: -

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Title: Dialogues in Clinical Neuroscience
  Alternative Title : Dialogues Clin Neurosci
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 6 (1) Sequence Number: - Start / End Page: 5 - 25 Identifier: ISSN: 1294-8322