摘要
在渐近混合模型中,混合现象发生在每一世代,通过对其混合连锁不平衡的理论分析,发现混合连锁不平衡与两 个子群体间的基因频率差成正比。基于这一点,构造了一个对重组率严格单调的函数(△ker=△/(p1-p2),其中△代表连锁不 平衡),进而据此推断标记基因座与疾病基因座的遗传连锁。应用人类基因组上不连锁的标记基因提供的连锁小平衡信息, 基于病人组数据构造了一个准似然比统计量。模拟结果显示,此检验可用于精确的基因定位。文章亦讨论了参数对检验的 影响。
Through the theoretical analysis of the admixture linkage disequilibrium (ALD) in the gradual admixture (GA) model, in which admixture occurs in every generation, the ALD is found to be proportional to the difference in marker allele frequencies, P1-P2, between two subpopulations. Based on this property, we can employ a strict monotonic function (△ker=△/( P1-P2 ), where △ denotes the linkage disequilibrium (LD)) of the recombination fraction between the marker locus and the disease locus to infer the true genetic linkage. We construct a quasi likelihood ratio test (LRT) for the case-only data utilizing the information of unlinked markers in the human genome. The simulation results show that our tests can be used to fine map a disease locus. The effects of parameter values in the ALD mapping are also discussed.
基金
This Work Was Supported by the Natural Science Foundation of China for Distinguished Young Scholars (No.10329102).