CAJ | 학술논문

研究QTL作图中零假设检验统计量分布特征,可以帮助我们选取合适的LOD临界值,以控制全基因组显著性概率水平下犯第一类错误的概率.本文利用模拟方法,研究了 QTL 作图中单个扫描位点的似然比检验(LRT)统计量在零假设下的分布特征、影响最大LOD统计量累积分布的因素以及不同群体在不同标记密度下有效独立检验次数与染色体长度的关系.结果表明,在定位加显性效应QTL的一维扫描和定位上位性互作QTL的二维扫描中,单个扫描位置上的LRT统计量均服从卡方分布,其自由度等于检测QTL遗传参数的个数;染色体个数、群体大小和表型测量误差方差对零假设下检验统计量的分布没有影响,即不影响LOD临界值的选取,而群体类型、标记密度和染色体长度有明显影响, BC1、RIL和F2三种类型的群体中, BC1群体的临界值最小, F2群体的临界值最大,标记越密染色体越长,对应的LOD临界值越大; QTL一维扫描中有效独立检验次数与染色体长度呈正比,二维扫描中有效独立检验次数与染色体长度呈二次幂关系.借助 Bonferroni 矫正,给出了全基因组显著性水平与单个扫描位点显著性水平间的关系,因此,研究者可根据作图群体的群体类型、标记密度和基因组长度,很方便地确定特定全局显著性概率水平下的LOD临界值.
연구QTL작도중령가설검험통계량분포특정,가이방조아문선취합괄적LOD림계치,이공제전기인조현저성개솔수평하범제일류착오적개솔.본문이용모의방법,연구료 QTL 작도중단개소묘위점적사연비검험(LRT)통계량재령가설하적분포특정、영향최대LOD통계량루적분포적인소이급불동군체재불동표기밀도하유효독립검험차수여염색체장도적관계.결과표명,재정위가현성효응QTL적일유소묘화정위상위성호작QTL적이유소묘중,단개소묘위치상적LRT통계량균복종잡방분포,기자유도등우검측QTL유전삼수적개수;염색체개수、군체대소화표형측량오차방차대령가설하검험통계량적분포몰유영향,즉불영향LOD림계치적선취,이군체류형、표기밀도화염색체장도유명현영향, BC1、RIL화F2삼충류형적군체중, BC1군체적림계치최소, F2군체적림계치최대,표기월밀염색체월장,대응적LOD림계치월대; QTL일유소묘중유효독립검험차수여염색체장도정정비,이유소묘중유효독립검험차수여염색체장도정이차멱관계.차조 Bonferroni 교정,급출료전기인조현저성수평여단개소묘위점현저성수평간적관계,인차,연구자가근거작도군체적군체류형、표기밀도화기인조장도,흔방편지학정특정전국현저성개솔수평하적LOD림계치.
Selecting an appropriate LOD threshold is of great interest in QTL mapping studies. Many approaches can be consid-ered to calculate the critical value throughout a genome, such as simulation-based method, analytical approximation, and empiri-cal method based on permutation test. Many tests are conducted in QTL mapping, which are not mutually independent because the linkage relationship of adjacent markers on chromosomes. In order to declare a significant QTL at a genome-wide significance level, it is necessary to understand the behavior of test statistic under null hypothesis in QTL mapping and to deal with the de-pendent multiple-test problem arising in the genome-wide test. Our objectives in this study were (1) to investigate the properties of LRT (likelihood ratio test) statistic of one-point scanning under null hypothesis in QTL mapping, (2) to determine the factors affecting the cumulative distribution of maximum LOD score, and (3) to identify the relationship between the effective number of independent tests and the length of chromosome by simulation method. Results indicated that the LRT test statistic in one-dimensional scanning of additive-dominant QTL and two-dimensional scanning of epistatic QTL followed chi-square distri-butions, and the degree of freedom (df) was equal to the number of genetic parameters to be estimated. For example, degree of freedom in recombinant inbred lines (RIL) population was equal to 1 in one dimensional or two dimensional scanning. Degree of freedom in F2 populations was equal to 2 in one-dimensional scanning and 4 in two-dimensional scanning. Number of chromo-some, population size and phenotyping error variance did not have any effect on the distribution of LRT under null hypothesis, and therefore will not affect the selection of LOD threshold. On the contrary, population type, genome size and marker density had significant impacts. For BC1, RIL, and F2 populations, the threshold was the smallest in BC1 population and the highest in F2 population. Higher marker density and longer chromosome resulted in higher LOD threshold. It was identified that the effective number of independent tests (Mef ) was proportional to the length of chromosome in one-dimensional scanning of addi-tive-dominant QTL. In two-dimensional scanning of epistatic QTL, it was identified that Mef was in a squared relationship to the length of chromosome. With the help of Bonferroni correction, we could acquire the relationship between point-wise and ge-nome-wide significance levels. Therefore, it is convenient to calculate the threshold LOD in QTL mapping, given the ge-nome-wide significance level, the population type, marker density and genome size.