Applicability of DNA pools on 500 K SNP microarrays for cost-effective initial screens in genomewide association studies.
Applicability of DNA pools on 500 K SNP microarrays for cost-effective initial screens in genomewide association studies.
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DOI：
10.1186/1471-2164-8-214
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发表时间：
2007-07-04
期刊：
影响因子：
4.4
通讯作者：
Plomin R
中科院分区：
文献类型：
--
作者：
Docherty SJ;Butcher LM;Schalkwyk LC;Plomin R
复杂性状的遗传影响被认为涉及多个效应量较小的数量性状基因座（QTL）。检测此类QTL关联需要在大样本群体中对大量DNA标记进行系统性筛选。利用单核苷酸多态性（SNP）微阵列上的混合DNA来筛选病例组和对照组等不同组之间的等位基因频率差异（称为SNP微阵列和混合法，或SNP - MaP）在10k和100k平台上都已被验证为一种有效的解决方案。我们证明这种方法可有效应用于真正的全基因组Affymetrix基因芯片®500K定位阵列。
在分别使用不同的Affymetrix基因芯片®500K定位阵列组对五个独立的DNA混合样本（每个样本池约200个样本）进行比较时，我们发现，对于次要等位基因频率>0.05的SNP，估计等位基因频率的排序可靠性（以不同DNA混合样本间等位基因频率估计值的平均相关性来评估）为0.948（五个样本池间的平均均值差异 = 0.069）。同样，SNP - MaP方法的有效性通过平均DNA混合样本等位基因频率估计值与60个无亲缘关系且单独进行基因分型的个体组成的独立（CEPH）样本的等位基因频率之间的排序相关性为0.937（平均均值差异 = 0.095）得以证明。
我们得出结论，SNP - MaP可扩展应用于Affymetrix基因芯片®500K定位阵列，为全基因组关联扫描中500K SNP微阵列提供一种具有成本效益、可靠且有效的初步筛选方法。
Genetic influences underpinning complex traits are thought to involve multiple quantitative trait loci (QTLs) of small effect size. Detection of such QTL associations requires systematic screening of large numbers of DNA markers within large sample populations. Using pooled DNA on SNP microarrays to screen for allelic frequency differences between groups such as cases and controls (called SNP Microarray and Pooling, or SNP-MaP) has been validated as an efficient solution on both 10 k and 100 k platforms. We demonstrate that this approach can be effectively applied to the truly genomewide Affymetrix GeneChip® Mapping 500 K Array. In comparisons between five independent DNA pools (N ~200 per pool) on separate Affymetrix GeneChip® Mapping 500 K Array sets, we show that, for SNPs with minor allele frequencies > 0.05, the reliability of the rank order of estimated allele frequencies, assessed as the average correlation between allele frequency estimates across the DNA pools, was 0.948 (average mean difference across the five pools = 0.069). Similarly, validity of the SNP-MaP approach was demonstrated by a rank-order correlation of 0.937 (average mean difference = 0.095) between the average DNA pool allele frequency estimates and the allele frequencies of an independent (CEPH) sample of 60 unrelated individually genotyped subjects. We conclude that SNP-MaP can be extended for use on the Affymetrix GeneChip® Mapping 500 K Array, providing a cost-effective, reliable and valid initial screen of 500 K SNP microarrays in genomewide association scans.
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微阵列上的基因分型DNA池：解决大型样品和大量SNP的QTL问题。
影响因子：
4.4
作者：
Meaburn, E;Butcher, LM;Liu, L;Fernandes, C;Hansen, V;Al-Chalabi, A;Plomin, R;Craig, I;Schalkwyk, LC
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