1. ¹Institute of Human Genetics, University of Bonn, Bonn, Germany
2. ²Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
3. ³Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany

Correspondence: Dr J Freudenberg, Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, D-53111 Bonn, Germany. Tel: +49 228 287 2581; Fax: +49 228 287 2380; E-mail: jan.freudenberg@uni-bonn.de

Received 1 September 2004; Revised 11 January 2005; Accepted 31 January 2005; Published online 5 April 2005.

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.