the complete linkage disequilibrium test a test that points to causative mutations underlying quantitative traits完整的连锁不平衡测试的测试点诱发突变潜在的量化特征.pdf

Uleberg and Meuwissen Genetics Selection Evolution 2011, 43:20 Ge n e t i c s /content/43/1/20 Se l e c t i o n Evolution RESEARCH Open Access The complete linkage disequilibrium test: a test that points to causative mutations underlying quantitative traits Eivind Uleberg1,2* and Theo HE Meuwissen1 Abstract Background: Genetically, SNP that are in complete linkage disequilibrium with the causative SNP cannot be distinguished from the causative SNP. The Complete Linkage Disequilibrium (CLD) test presented here tests whether a SNP is in complete LD with the causative mutation or not. The performance of the CLD test is evaluated in 1000 simulated datasets. Methods: The CLD test consists of two steps i.e. analysis I and analysis II. Analysis I consists of an association analysis of the investigated region. The log-likelihood values from analysis I are next ranked in descending order and in analysis II the CLD test evaluates differences in log-likelihood ratios between the best and second best markers. Under the null-hypothesis distribution, the best SNP is in greater LD with the QTL than the second best, while under the alternative-CLD-hypothesis, the best SNP is alike-in-state with the QTL. To find a significance threshold, the test was also performed on data excluding the causative SNP. The 5th, 10th and 50th highest TCLD value from 1000 replicated analyses were used to control the type-I-error rate of the test at p = 0.005, p = 0.01 and p = 0.05, respectively. Results: In a situation where the QTL explained 48% of the phenotyp