GeneScreen: a program for high-throughput mutation detection in DNA sequence electropherograms

Ian M Carr (1) , Nick Camm (2) , Graham R Taylor (1) , Ruth Charlton (2) , Sian Ellard (3) , Eamonn G Sheridan (1) , Alexander F Markham (1) , David T Bonthron (1)

1 LIMM
2 St. James's University Hospital
3 Royal Devon and Exeter Foundation Trust

Background While massively parallel DNA sequencing methods continue to evolve rapidly, the benchmark technique for detection and verification of rare (particularly disease-causing) sequence variants remains four-colour dye-terminator sequencing by capillary electrophoresis. The high throughput and long read lengths currently available have shifted the bottleneck in mutation detection away from data generation to data analysis. While excellent computational methods have been developed for quantifying sequence accuracy and detecting variants, either during de novo sequence assembly or for SNP detection, the identification, verification and annotation of very rare sequence variants remains a rather labour-intensive process for which few software aids exist. Results Here we describe GeneScreen, a program that analyses capillary electropherograms and compares their sequences to a known reference for identification of mutations. The detected sequence variants are then made available for rapid assessment and annotation via a graphical user interface, allowing any selected variants to be exported for reporting and archiving. Conclusion Using GeneScreen, a single user requires only a few minutes to identify rare mutations in hundreds of sequence traces, with comparable sensitivity to expensive commercial products.

Mots clés: Diagnostics; Genetics; Genetic screening/counselling; Molecular genetics

Ian M Carr, Nick Camm, Graham R Taylor, Ruth Charlton, Sian Ellard, et al.. GeneScreen: a program for high-throughput mutation detection in DNA sequence electropherograms. Journal of Medical Genetics, 2010, 48 (2), pp.123. ⟨10.1136/jmg.2010.082081⟩. ⟨hal-00581005⟩