This article is part of the supplement: Genetic Analysis Workshop 17: Unraveling Human Exome Data
Strategies for selection of subjects for sequencing after detection of a linkage peak
1 Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah, 391 Chipeta Way, Suite D, Salt Lake City, UT 84105, USA
2 George E. Wallen Department of Veterans Affairs Medical Center, 500 Foothill Drive, Salt Lake City, UT 84148, USA
BMC Proceedings 2011, 5(Suppl 9):S77 doi:10.1186/1753-6561-5-S9-S77Published: 29 November 2011
Linkage analysis has the potential to localize disease genes of interest, but the choice of which subjects to select for follow-up sequencing after identifying a linkage peak might influence the ability to find a disease gene. We compare nine different strategies for selection of subjects for follow-up sequencing using sequence data from the Genetic Analysis Workshop 17. We found that our more selective strategies, which included methods to identify case subjects more likely to be affected by genetic causes, out-performed sequencing all case and control subjects in linked pedigrees and required sequencing fewer individuals. We found that using genotype data from population control subjects had a higher benefit-cost ratio than sequencing control subjects selected as being the opposite extreme of the case subjects. We conclude that choosing case subjects for sequencing based on more selective strategies can be reliable and cost-effective.