Axenovich Tatiana I, Zorkoltseva Irina V, Liu Fan, Kirichenko Anatoly V, Aulchenko Yurii S
Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, Novosibirsk, Russia.
Hum Hered. 2008;65(2):57-65. doi: 10.1159/000108937. Epub 2007 Sep 26.
For pedigrees with multiple loops, exact likelihoods could not be computed in an acceptable time frame and thus, approximate methods are used. Some of these methods are based on breaking loops and approximations of complex pedigree likelihoods using the exact likelihood of the corresponding zero-loop pedigree. Due to ignoring loops, this method results in a loss of genetic information and a decrease in the power to detect linkage. To minimize this loss, an optimal set of loop breakers has to be selected. In this paper, we present a graph theory based algorithm for automatic selection of an optimal set of loop breakers. We propose using a total relationship between measured pedigree members as a proxy to power. To minimize the loss of genetic information, we suggest selection of such breakers whose duplication in a pedigree would be accompanied by a minimal loss of total relationship between measured pedigree members. We show that our algorithm compares favorably with other existing loop-breaker selection algorithms in terms of conservation of genetic information, statistical power and CPU time of subsequent linkage analysis. We implemented our method in a software package LOOP_EDGE, which is available at http://mga.bionet.nsc.ru/nlru/.
对于具有多个环的家系，无法在可接受的时间范围内计算精确似然值，因此使用近似方法。其中一些方法基于打破环，并利用相应零环家系的精确似然值对复杂家系似然值进行近似。由于忽略了环，这种方法会导致遗传信息丢失以及连锁检测能力下降。为了使这种损失最小化，必须选择一组最优的环打破者。在本文中，我们提出了一种基于图论的算法，用于自动选择一组最优的环打破者。我们建议使用被测家系成员之间的总关系作为能力的代理指标。为了使遗传信息的损失最小化，我们建议选择这样的打破者，即在一个家系中重复这些打破者时，被测家系成员之间的总关系损失最小。我们表明，在遗传信息的保留、统计能力以及后续连锁分析的CPU时间方面，我们的算法优于其他现有的环打破者选择算法。我们在一个名为LOOP_EDGE的软件包中实现了我们的方法，该软件包可在http://mga.bionet.nsc.ru/nlru/获取。
