Beckmann Lars, Ziegler Andreas, Duggal Priya, Bailey-Wilson Joan E
German Cancer Research Center (Deutsches Krebsforschungszontrum) DKFZ, Heidelberg, Germany.
Genet Epidemiol. 2005;29 Suppl 1:S59-71. doi: 10.1002/gepi.20111.
Moderately dense maps of single-nucleotide polymorphism (SNP) markers across the human genome for both the simulated data set and data from the Collaborative Study of the Genetics of Alcoholism were available at Genetic Analysis Workshop 14 for the first time. This allowed examination of various novel and existing methods for haplotype analyses. Three contributors applied Mantel statistics in different ways for both linkage and association analysis by using the shared length between two haplotypes at a marker locus as a measure of genetic similarity. The results indicate that haplotype-sharing based on Mantel statistics can be a powerful approach and needs further methodological evaluation. Four contributors investigated haplotype-tagging SNP (htSNP) selection procedures, two contributors examined the use of multilocus haplotypes compared to single loci in association tests, and two contributors compared the accuracy of various methods for reconstructing haplotypes and estimating haplotype frequencies for both pedigree data and data from unrelated individuals. For all three different tasks, software packages and procedures gave similar results in regions of high linkage disequilibrium (LD). However, they were not as consistent in regions of moderate to low LD. One coalescence-based approach for estimating haplotype frequencies, coupled with a Markov chain Monte Carlo technique, outperformed the other haplotype frequency estimation methods in regions of low LD. In conclusion, regardless of the task, results were similar in chromosomal regions of high LD. However, based on the differing results observed here, methodological improvements are required for chromosomal regions of low to moderate LD.
在遗传分析研讨会14上首次获得了针对模拟数据集以及来自酒精中毒遗传学合作研究的数据的、覆盖人类基因组的中等密度单核苷酸多态性（SNP）标记图谱。这使得对各种新的和现有的单倍型分析方法进行检验成为可能。三位研究者通过将标记位点处两个单倍型之间的共享长度作为遗传相似性的一种度量，以不同方式将Mantel统计量应用于连锁分析和关联分析。结果表明，基于Mantel统计量的单倍型共享可能是一种强有力的方法，需要进一步进行方法学评估。四位研究者研究了单倍型标签SNP（htSNP）选择程序，两位研究者在关联检验中比较了多位点单倍型与单一位点的使用情况，还有两位研究者比较了各种用于重建单倍型和估计系谱数据及无关个体数据的单倍型频率的方法的准确性。对于所有这三项不同任务，在高连锁不平衡（LD）区域，软件包和程序给出了相似的结果。然而，在中低LD区域它们的一致性较差。一种基于合并的估计单倍型频率的方法，结合马尔可夫链蒙特卡罗技术，在低LD区域优于其他单倍型频率估计方法。总之，无论任务如何，在高LD的染色体区域结果相似。然而，基于此处观察到的不同结果，中低LD的染色体区域需要进行方法学改进。
