Assessment and implications of linkage disequilibrium in genome-wide single-nucleotide polymorphism and microsatellite panels
Assessment and implications of linkage disequilibrium in genome-wide single-nucleotide polymorphism and microsatellite panels
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DOI：
10.1002/gepi.20112
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发表时间：
2005-01-01
影响因子：
2.1
通讯作者：
Jarvik, GP
中科院分区：
文献类型：
--
作者：
Goode, EL;Jarvik, GP
标记之间的连锁不平衡 (LD) 更有可能存在于密集的全基因组单核苷酸多态性 (SNP) 组中，而不是微卫星组中。作为遗传分析研讨会 14 (GAW14) 的一部分，使用酒精中毒遗传学合作研究 (COGA) 的数据评估了 Illumina 连接面板 III 和 Affymetrix Genechip (R) 10 K 映射阵列中 LID 的程度。在 COGA 和模拟数据中检查了 LD 对连锁结果的影响，并评估了 SNP 的特征，以确定其检测群体亚结构和预测单倍型的能力。此处总结的论文作者观察到 Affymetrix 中的 LD 高于 Illumina panel，可能是由于 Affymetrix panel 中标记密度增加，并且发现 X 染色体上的 LID 高于常染色体上的 LID。模拟分析表明，标记间 LD 会导致连锁统计数据出现向上偏差；然而，LD 对连锁分析的影响取决于未基因型创始人的比例和 LD 的程度。在 COGA 分析中未观察到 LD 对连锁峰的大影响。此外，本文总结的论文发现，与微卫星相比，具有高次要等位基因频率的 SNP 在检测群体亚结构方面信息量最大，而 LID 较高的 SNP 和少量 SNP 对于单倍型预测最可靠。随着基因分型的便利性不断提高，连锁和关联研究（包括全基因组关联研究）的研究设计和 SNP 选择将得到改进，同时考虑所研究的特定人群的 LD。
Linkage disequilibrium (LD) between markers is more likely to exist in dense genome-wide single-nucleotide polymorphism (SNP) panels than in microsatellite panels. As part of Genetic Analysis Workshop 14 (GAW14), the extent of LID in the Illumina linkage panel III and the Affymetrix Genechip (R) 10 K mapping array was assessed, using data from the Collaborative Study on the Genetics of Alcoholism (COGA). The impact of LD on linkage results was examined in COGA and simulated data, and characteristics of SNPs were assessed for their ability to detect population substructure and predict haplotypes. The authors of the papers summarized here observed greater LD in the Affymetrix than in the Illumina panel, possibly due to increased marker density in the Affymetrix panel, and found greater LID on chromosome X than on the autosomes. Simulation analyses suggest that intermarker LD can cause an upward bias in linkage statistics; however, the impact of LD on linkage analysis depends on the proportion of ungenotyped founders and the extent of LD. No large effect of LD on linkage peaks was observed in COGA analyses. In addition, the papers summarized here found that SNPs with high minor allele frequencies were the most informative compared with microsatellites for the detection of population substructure, and that SNPs in higher LID, and small numbers of SNPs, were the most reliable for haplotype prediction. As ease of genotyping continues to increase, study design and SNP selection for linkage and association studies (including genome-wide association studies) will be improved with consideration of LD in the particular populations studied.