Ekstrøm C T
Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
Genet Epidemiol. 2001 Dec;21(4):285-98. doi: 10.1002/gepi.1035.
Multipoint linkage analysis gives increased power over single-point analysis to detect linkage for quantitative trait loci (QTL). Besides increased power, the use of multipoint methods makes it possible to estimate not only the location but also the magnitude of the QTL. Currently, two methods are commonly used for calculating multipoint identity-by-descent (IBD) allele-sharing estimates for pedigrees of moderate sizes. The method of Fulker et al. is based on multiple regression of the IBD status at the observed marker loci, whereas the hidden Markov model approach of Kruglyak and Lander estimates the true inheritance distribution at each chromosomal location. Simulation studies of full sibs and nuclear pedigrees show that the two methods for estimating multipoint IBD scores may give very different estimates for a pair of relatives and that a small increase in power to detect linkage can be obtained by using the hidden Markov model compared with the regression method.
多点连锁分析相比于单点分析,在检测数量性状基因座(QTL)的连锁方面具有更强的功效。除了功效增强外,使用多点方法不仅能够估计QTL的位置,还能估计其大小。目前,有两种方法常用于计算中等规模家系的多点同源相同(IBD)等位基因共享估计值。Fulker等人的方法基于观察到的标记位点处IBD状态的多元回归,而Kruglyak和Lander的隐马尔可夫模型方法则估计每个染色体位置的真实遗传分布。对全同胞和核心家系的模拟研究表明,这两种估计多点IBD分数的方法对于一对亲属可能会给出非常不同的估计值,并且与回归方法相比,使用隐马尔可夫模型在检测连锁时能获得稍高的功效。