National Human Genome Center, Howard University, Washington, DC 20059, USA.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S16. doi: 10.1186/1471-2156-6-S1-S16.
The central issue for Genetic Analysis Workshop 14 (GAW14) is the question, which is the better strategy for linkage analysis, the use of single-nucleotide polymorphisms (SNPs) or microsatellite markers? To answer this question we analyzed the simulated data using Duffy's SIB-PAIR program, which can incorporate parental genotypes, and our identity-by-state - identity-by-descent (IBS-IBD) transformation method of affected sib-pair linkage analysis which uses the matrix transformation between IBS and IBD. The advantages of our method are as follows: the assumption of Hardy-Weinberg equilibrium is not necessary; the parental genotype information maybe all unknown; both IBS and its related IBD transformation can be used in the linkage analysis; the determinant of the IBS-IBD transformation matrix provides a quantitative measure of the quality of the marker in linkage analysis. With the originally distributed simulated data, we found that 1) for microsatellite markers there are virtually no differences in types I and II error rates when parental genotypes were or were not used; 2) on average, a microsatellite marker has more power than a SNP marker does in linkage detection; 3) if parental genotype information is used, SNP markers show lower type I error rates than microsatellite markers; and 4) if parental genotypes are not available, SNP markers show considerable variation in type I error rates for different methods.
遗传分析工作坊 14(GAW14)的核心问题是,对于连锁分析来说,使用单核苷酸多态性(SNP)还是微卫星标记更好?为了回答这个问题,我们使用 Duffy 的 SIB-PAIR 程序对模拟数据进行了分析,该程序可以整合父母的基因型,以及我们的基于状态的同一性-基于血统的(IBS-IBD)关联分析变换方法,该方法使用 IBS 和 IBD 之间的矩阵变换。我们的方法的优点如下:1. 不需要 Hardy-Weinberg 平衡假设;2. 父母的基因型信息可能完全未知;3. 可以在连锁分析中同时使用 IBS 和相关的 IBD 变换;4. IBS-IBD 变换矩阵的行列式提供了标记在连锁分析中的质量的定量度量。使用原始分布的模拟数据,我们发现:1. 对于微卫星标记,使用或不使用父母基因型时,I 型和 II 型错误率几乎没有差异;2. 平均而言,微卫星标记在连锁检测中比 SNP 标记具有更高的功效;3. 如果使用父母基因型信息,SNP 标记比微卫星标记具有更低的 I 型错误率;4. 如果无法获得父母基因型,则 SNP 标记在不同方法的 I 型错误率方面存在相当大的变化。