Program in Genetics and Genomic Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S155. doi: 10.1186/1471-2156-6-S1-S155.
Homozygosity outlier loci, which show patterns of variation that are extremely divergent from the rest of the genome, can be evaluated by comparison of the homozygosity under Hardy-Weinberg proportions (the sum of the squares of allele frequencies) with the expected homozygosity under neutrality. Such outlier loci are potentially under selection (balancing selection or directional selection) when genome-wide effects (such as bottleneck and rapid population growth) are excluded. Outlier loci show skewed allele frequencies with respect to neutrality and may therefore affect the identification of pedigree errors. However, choosing neutral markers (excluding outlier loci) for the identification of pedigree errors has been neglected thus far. Our results showed that 4.1%, 5.5%, and 1.5% of the microsatellite markers, Illumina single-nucleotide polymorphisms (SNPs), and Affymetrix SNPs, respectively, on the autosomes appear to be under balancing selection (p <or= 0.01) while 0.8% of the Affymetrix SNPs are consistent with directional selection. On the X-chromosome, 7.7%, 3.2%, and 0.4% of the microsatellite markers, Illumina SNPs, and Affymetrix SNPs, respectively, appear to be under balancing selection. 9.3% of Illumina SNPs and 6.7% of Affymetrix SNPs which have high minor allele frequency (>or=40%) appear to be under balancing selection. Pedigree structure errors in 15 of 143 pedigrees were detected using microsatellite markers from the autosomes and/or selected SNPs from chromosomes 1 to 18 of the Illumina and/or selected SNPs from chromosomes 1 to 16 of the Affymetrix. Outlier loci did not make a major difference to the identification of pedigree errors. The Collaborative Study on the Genetics of Alcoholism data has pedigree errors and some of them may be due to sample mix up.
纯合子离群位点表现出与基因组其他部分极其不同的变异模式，可以通过比较哈迪-温伯格比例（等位基因频率的平方和）下的纯合度与中性条件下的预期纯合度来评估。在排除全基因组效应（如瓶颈和快速种群增长）的情况下，这些离群位点可能受到选择（平衡选择或定向选择）的影响。离群位点的等位基因频率相对于中性存在偏倚，因此可能会影响家系错误的识别。然而，迄今为止，选择中性标记（排除离群位点）来识别家系错误一直被忽视。我们的结果表明，常染色体上的微卫星标记、Illumina 单核苷酸多态性（SNP）和 Affymetrix SNP 分别有 4.1%、5.5%和 1.5%似乎受到平衡选择（p≤0.01）的影响，而 0.8%的 Affymetrix SNP 与定向选择一致。在 X 染色体上，微卫星标记、Illumina SNP 和 Affymetrix SNP 分别有 7.7%、3.2%和 0.4%似乎受到平衡选择的影响。Illumina SNP 中有 9.3%，Affymetrix SNP 中有 6.7%的次要等位基因频率（>或=40%）较高的 SNP 似乎受到平衡选择的影响。使用来自常染色体的微卫星标记和/或来自 Illumina 的染色体 1 到 18 上的选定 SNP 和/或来自 Affymetrix 的染色体 1 到 16 上的选定 SNP，在 143 个家系中的 15 个家系中检测到了家系结构错误。离群位点对家系错误的识别没有产生重大影响。合作酒精中毒遗传学研究数据存在家系错误，其中一些可能是由于样本混淆造成的。
