Effectiveness of computational methods in haplotype prediction
Effectiveness of computational methods in haplotype prediction
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DOI：
10.1007/s00439-001-0656-4
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发表时间：
2002-02-01
期刊：
影响因子：
5.3
通讯作者：
Purvis, IJ
中科院分区：
文献类型：
--
作者：
Xu, CF;Lewis, K;Purvis, IJ
单倍型分析已被用于缩小疾病易感基因的位置，并用于研究许多种群过程。已经开发了计算算法来估计单倍型频率，并根据无关个体的基因数据预测单倍型阶段。然而，在提倡这些计算方法的应用之前，需要对它们的准确性进行评估。我们在实验中测定了N-乙酰转移酶2基因(NAT2,850bp，n=81)和X染色体上一个140kb的区域(n=77)的单倍型，每个区域都包含5个单核苷酸多态(SNPs)。我们对减法、期望最大化(EM)法和相位法在单倍型频率估计和单倍型相位预测中的精度进行了实证评估和比较。在SNPs(NAT2基因)之间存在几乎完全的链接年龄不平衡(LD)的情况下，所有这三种方法都提供了有效和准确的单倍型频率和单倍型阶段的估计。对于没有标记的LD的基因组区域(染色体X位点)，计算方法足以估计总体单倍型频率。然而，在预测个体单倍型阶段方面，没有一种方法是准确的。EM和阶段法对两个基因组区域的总单倍型频率提供了比减法更好的估计。
Haplotype analysis has been used for narrowing down the location of disease-susceptibility genes and for investigating many population processes. Computational algorithms have been developed to estimate haplotype frequencies and to predict haplotype phases from genotype data for unrelated individuals. However, the accuracy of such computational methods needs to be evaluated before their applications can be advocated. We have experimentally determined the haplotypes at two loci, the N-acetyltransferase 2 gene (NAT2, 850 bp, n=81) and a 140-kb region on chromosome X (n=77), each consisting of five single nucleotide polymorphisms (SNPs). We empirically evaluated and compared the accuracy of the subtraction method, the expectation-maximisation (EM) method, and the PHASE method in haplotype frequency estimation and in haplotype phase prediction. Where there was near complete link-age disequilibrium (LD) between SNPs (the NAT2 gene), all three methods provided effective and accurate estimates for haplotype frequencies and individual haplotype phases. For a genomic region in which marked LD was not maintained (the chromosome X locus), the computational methods were adequate in estimating overall haplotype frequencies. However, none of the methods was accurate in predicting individual haplotype phases. The EM and the PHASE methods provided better estimates for overall haplotype frequencies than the subtraction method for both genomic regions.