Effectiveness of computational methods in haplotype prediction

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• 作者：Chun-Fang Xu ; Karen Lewis ; Kathryn L. Cantone ; Parveen Khan ; Christine Donnelly ; Nicola White ; Nikki Crocker ; Pete R. Boyd ; Dmitri V. Zaykin and Ian J. Purvis
• 刊名：Human Genetics
• 出版年：2002
• 出版时间：February 2002
• 年：2002
• 卷：110
• 期：2
• 页码：148-156
• 全文大小：76 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Molecular Medicine
  Internal Medicine
  Metabolic Diseases
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1203

文摘

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 linkage 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.