Allen-Brady Kristina, Farnham James, Cannon-Albright Lisa
Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah, 391 Chipeta Way, Suite D, Salt Lake City, UT 84105, USA.
Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah, 391 Chipeta Way, Suite D, Salt Lake City, UT 84105, USA ; George E. Wallen Department of Veterans Affairs Medical Center, 500 Foothill Drive, Salt Lake City, UT 84148, USA.
BMC Proc. 2011 Nov 29;5 Suppl 9(Suppl 9):S77. doi: 10.1186/1753-6561-5-S9-S77. eCollection 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.
连锁分析有潜力定位感兴趣的疾病基因，但在确定连锁峰后选择哪些受试者进行后续测序可能会影响找到疾病基因的能力。我们使用遗传分析研讨会17的序列数据，比较了九种不同的选择受试者进行后续测序的策略。我们发现，我们更具选择性的策略，包括识别更可能受遗传因素影响的病例受试者的方法，比在连锁家系中对所有病例和对照受试者进行测序表现更好，且所需测序的个体更少。我们发现，使用来自人群对照受试者的基因型数据比测序被选为病例受试者相反极端的对照受试者具有更高的效益成本比。我们得出结论，基于更具选择性的策略选择病例受试者进行测序是可靠且具有成本效益的。
