Browning Sharon R
Department of Statistics, The University of Auckland, Auckland 92019, New Zealand.
Am J Hum Genet. 2006 Jun;78(6):903-13. doi: 10.1086/503876. Epub 2006 Apr 7.
I propose a new method for association-based gene mapping that makes powerful use of multilocus data, is computationally efficient, and is straightforward to apply over large genomic regions. The approach is based on the fitting of variable-length Markov chain models, which automatically adapt to the degree of linkage disequilibrium (LD) between markers to create a parsimonious model for the LD structure. Edges of the fitted graph are tested for association with trait status. This approach can be thought of as haplotype testing with sophisticated windowing that accounts for extent of LD to reduce degrees of freedom and number of tests while maximizing information. I present analyses of two published data sets that show that this approach can have better power than single-marker tests or sliding-window haplotypic tests.
我提出了一种基于关联的基因定位新方法,该方法能有效利用多位点数据,计算效率高,且易于应用于大型基因组区域。该方法基于可变长度马尔可夫链模型的拟合,该模型能自动适应标记间的连锁不平衡(LD)程度,从而为LD结构创建一个简洁的模型。对拟合图的边进行与性状状态的关联测试。这种方法可以被认为是一种具有复杂窗口设置的单倍型测试,该窗口设置考虑了LD的程度,以减少自由度和测试次数,同时最大化信息。我展示了对两个已发表数据集的分析,结果表明该方法比单标记测试或滑动窗口单倍型测试具有更好的功效。