Availability of high quality SNP data is a rate‐limiting factor in understanding the impact of genetic variability on gene function and phenotype. Although global projects like HAPMAP generate large numbers of SNPs in an even spacing throughout the human genome, many variation studies have a more focused approach: in the follow‐up of positional association findings, candidate gene studies, and functional genomics experiments, knowledge of all variations in a limited amount of sequence (e.g., a gene) is needed. This leads to a large number of resequencing experiments, for which there is a surprising lack of analysis software. We have thus developed specialized software (InSNP) for targeted mutation detection and compared its performance to Polyphred and Mutation Surveyor using 28 amplicons. Out of a total of 579 (InSNP), 644 (Polyphred), and 526 (Mutation Surveyor) SNP predictions, 39 SNPs were confirmed by human expert inspection, with five SNPs missed by Polyphred and one missed by InSNP using the default settings. For InDel detection, out of 70 (InSNP), 28 (Polyphred), and 693 (Mutation Surveyor) InDel predictions, two InDels were confirmed by human expert inspection, with one InDel missed by Polyphred. InSNP provides a user‐friendly interface with better functionality for mutation detection than general‐purpose sequence handling software. It provides similar SNP detection sensitivity and specificity as the public domain and commercial alternatives in the investigated dataset. We hope that InSNP lowers the barriers to the use of automated mutation detection software and aids in the improvement of the efficiency of such experiments. The Windows installer (setup) program and sample datasets are available at www.mucosa.de/insnp/. Hum Mutat 26(1), 11–19, 2005. © 2005 Wiley‐Liss, Inc.
[1]
A. Pertsemlidis,et al.
ELXR: a resource for rapid exon-directed sequence analysis
,
2004,
Genome Biology.
[2]
J. Couzin.
Consensus Emerges on HapMap Strategy
,
2004,
Science.
[3]
Yusuke Nakamura,et al.
Gene-based SNP discovery as part of the Japanese Millennium Genome Project: identification of 190 562 genetic variations in the human genome
,
2002,
Journal of Human Genetics.
[4]
D. Nickerson,et al.
PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing.
,
1997,
Nucleic acids research.
[5]
Ben Shneiderman,et al.
Image-Browser Taxonomy and Guidelines for Designers
,
1995,
IEEE Softw..
[6]
M. Daly,et al.
High-resolution haplotype structure in the human genome
,
2001,
Nature Genetics.
[7]
Ben Shneiderman,et al.
Readings in information visualization - using vision to think
,
1999
.
[8]
P. Green,et al.
Consed: a graphical tool for sequence finishing.
,
1998,
Genome research.
[9]
Circe W. Tsui,et al.
Single nucleotide polymorphisms (SNPs) that map to gaps in the human SNP map.
,
2003,
Nucleic acids research.
[10]
Pui-Yan Kwok,et al.
Efficient high-throughput resequencing of genomic DNA.
,
2003,
Genome research.