Ohashi Jun, Tokunaga Katsushi
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
J Hum Genet. 2003;48(9):487-491. doi: 10.1007/s10038-003-0058-7. Epub 2003 Aug 22.
Linkage disequilibrium (LD) testing is often used in the search for disease genes. In this study, we developed a method for calculating the expected power of genome-wide LD testing by using microsatellite markers under the following assumptions: (1) microsatellite markers have unequally frequent alleles, (2) markers are equally spaced through the human genome, (3) the degree of LD between the disease variant and the marker decays gradually because of recombination and mutation, (4) the population frequency of the disease variant is low (e.g., 0.05), (5) a single-marker test is performed in a case-control study, and (6) the significance level is adjusted by the number of tests to avoid inflation of the type I error. Our calculations revealed a markedly higher power for microsatellite markers than for single nucleotide polymorphism (SNP) markers, even if more SNPs are analyzed, suggesting that the use of microsatellite markers is preferable to the use of SNPs for genome-wide screening under the above assumptions. This method will be helpful to researchers who design genome-wide LD testing with microsatellite markers.
连锁不平衡（LD）检测常用于寻找疾病基因。在本研究中，我们开发了一种方法，用于在以下假设下通过使用微卫星标记计算全基因组LD检测的预期效能：（1）微卫星标记的等位基因频率不等；（2）标记在人类基因组中均匀分布；（3）由于重组和突变，疾病变异体与标记之间的LD程度逐渐衰减；（4）疾病变异体的群体频率较低（例如0.05）；（5）在病例对照研究中进行单标记检测；（6）通过检测次数调整显著性水平以避免I型错误膨胀。我们的计算结果显示，即使分析了更多的单核苷酸多态性（SNP）标记，微卫星标记的效能仍显著高于SNP标记，这表明在上述假设下，在全基因组筛查中使用微卫星标记优于使用SNP标记。该方法将有助于设计使用微卫星标记进行全基因组LD检测的研究人员。
