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Estimation of statistical power and false discovery rate of QTL mapping methods through computer simulation
  • ISSN号:2095-1353
  • 期刊名称:《应用昆虫学报》
  • 时间:0
  • 分类:O212.1[理学—概率论与数理统计;理学—数学]
  • 作者机构:[1]中国农业科学院作物科学研究所,农作物基因资源与基因改良国家重大科学工程,CIMMYT中国办事处,北京100081
  • 相关基金:本研究由国家自然科学基金项目(31000540)资助.
中文摘要:

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,BC、RIL和F2三种类型的群体中,BC。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问的关系,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。

英文摘要:

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 (d~ 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 Fz populations, the threshold was the smallest in BC1 population and the highest in F2 population.

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期刊信息
  • 《应用昆虫学报》
  • 中国科技核心期刊
  • 主管单位:中国科学院
  • 主办单位:中国昆虫学会 中国科学院动物研究所
  • 主编:戈峰
  • 地址:北京朝阳区北辰西路1号院5号中科院动物所
  • 邮编:100101
  • 邮箱:entom@ioz.ac.cn
  • 电话:010-64807137
  • 国际标准刊号:ISSN:2095-1353
  • 国内统一刊号:ISSN:11-6020/Q
  • 邮发代号:2-151
  • 获奖情况:
  • 96、2000年获中科院《优秀期刊三等奖》,92年获中国科协《优秀学术期刊一等奖》,2001进入“中国期刊”方阵,“双百”期刊,排名第96位
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),英国农业与生物科学研究中心文摘,美国剑桥科学文摘,美国生物科学数据库,英国动物学记录,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2011版),中国北大核心期刊(2014版)
  • 被引量:3170