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Systematic investigation of genetic variability in 111 human genes—implications for studying variable drug response

The Pharmacogenomics Journal volume 5, pages 183–192 (2005)Cite this article

Abstract

In order to identify single-nucleotide polymorphisms (SNPs) and analyze their characteristics in a set of 111 genes, we resequenced exons and flanking regions in an average of 170 chromosomes from individuals of European origin. Genetic variability was decreased in noncoding regions highly conserved between human and rodents, indicating functional relevance of these regions. Furthermore, diversity of coding nonsynonymous SNPs was found lower in regions encoding a known protein sequence motif. SNPs predicted to be of functional significance were more common amongst rare variants. Despite the significant recent growth of SNP numbers in public SNP databases, only a small fraction of these rare variants is represented. This may be relevant in the investigation of the genetic causes of severe side effects, for which rare variants are plausible candidates. Estimation of htSNPs reduces the genotyping effort required in capturing common haplotypes, for certain genes, however, this accounts for only a small fraction of haplotype diversity.

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Acknowledgements

We thank Dr Christine Braeman for help in preparing the manuscript. This work was supported by grants from the German Human Genome Project (DHGP) and the German National Genome Research Network (NGFN).

Author information

Authors and Affiliations

  1. Institute of Human Genetics, University of Bonn, Bonn, Germany

    Y Freudenberg-Hua, J Freudenberg, J Winantea, N Kluck, S Cichon, P Propping & M M Nöthen

  2. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    S Cichon & M M Nöthen

  3. Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany

    M Brüss

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  1. Y Freudenberg-Hua
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  2. J Freudenberg
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  7. P Propping
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Corresponding author

Correspondence to J Freudenberg.

Additional information

Database submission: All SNPs were submitted to dbSNP with complete genotype and flanking sequence information (ss12586678–ss12587076, ss28447039-ss28447415).

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None declared.

Supplementary Information

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj).

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Freudenberg-Hua, Y., Freudenberg, J., Winantea, J. et al. Systematic investigation of genetic variability in 111 human genes—implications for studying variable drug response. Pharmacogenomics J 5, 183–192 (2005). https://doi.org/10.1038/sj.tpj.6500306

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