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利用两个高密度单核苷酸多态性图谱面板评估连锁不平衡及其对非参数多点连锁分析的影响。

Evaluation of linkage disequilibrium and its effect on non-parametric multipoint linkage analysis using two high density single-nucleotide polymorphism mapping panels.

机构信息

Illumina, Inc, 9885 Towne Centre Drive, San Diego, CA 92121, USA.

出版信息

BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S85. doi: 10.1186/1471-2156-6-S1-S85.

Abstract

Genotype data from the Illumina Linkage III SNP panel (n = 4,720 SNPs) and the Affymetrix 10 k mapping array (n = 11,120 SNPs) were used to test the effects of linkage disequilibrium (LD) between SNPs in a linkage analysis in the Collaborative Study on the Genetics of Alcoholism pedigree collection (143 pedigrees; 1,614 individuals). The average r2 between adjacent markers across the genetic map was 0.099 +/- 0.003 in the Illumina III panel and 0.17 +/- 0.003 in the Affymetrix 10 k array. In order to determine the effect of LD between marker loci in a nonparametric multipoint linkage analysis, markers in strong LD with another marker (r2 > 0.40) were removed (n = 471 loci in the Illumina panel; n = 1,804 loci in the Affymetrix panel) and the linkage analysis results were compared to the results using the entire marker sets. In all analyses using the ALDX1 phenotype, 8 linkage regions on 5 chromosomes (2, 7, 10, 11, X) were detected (peak markers p < 0.01), and the Illumina panel detected an additional region on chromosome 6. Analysis of the same pedigree set and ALDX1 phenotype using short tandem repeat markers (STRs) resulted in 3 linkage regions on 3 chromosomes (peak markers p < 0.01). These results suggest that in this pedigree set, LD between loci with spacing similar to the SNP panels tested may not significantly affect the overall detection of linkage regions in a genome scan. Moreover, since the data quality and information content are greatly improved in the SNP panels over STR genotyping methods, new linkage regions may be identified due to higher information content and data quality in a dense SNP linkage panel.

摘要

使用 Illumina Linkage III SNP 面板(n = 4720 个 SNP)和 Affymetrix 10 k 图谱数组(n = 11120 个 SNP)的基因型数据,在酒精遗传谱系收集的合作研究(143 个家系;1614 个人)中进行连锁分析,以测试 SNP 之间连锁不平衡(LD)的影响。在 Illumina III 面板中,遗传图谱上相邻标记之间的平均 r2 为 0.099 +/- 0.003,在 Affymetrix 10 k 图谱中为 0.17 +/- 0.003。为了确定标记位点之间 LD 在非参数多点连锁分析中的影响,与另一个标记(r2 > 0.40)强烈连锁的标记(n = 471 个 Illumina 面板;n = 1804 个 Affymetrix 面板)被删除,并且将连锁分析结果与使用整个标记集的结果进行比较。在使用 ALDX1 表型的所有分析中,在 5 条染色体(2、7、10、11、X)上检测到 8 个连锁区域(峰值标记 p < 0.01),并且 Illumina 面板在 6 号染色体上检测到另外一个区域。使用短串联重复标记(STR)对相同的家系集和 ALDX1 表型进行分析,在 3 条染色体上检测到 3 个连锁区域(峰值标记 p < 0.01)。这些结果表明,在这个家系集中,与测试的 SNP 面板间距相似的位点之间的 LD 可能不会显著影响基因组扫描中连锁区域的总体检测。此外,由于 SNP 面板中的数据质量和信息量大大提高,由于密集 SNP 连锁面板中的信息量和数据质量更高,可能会发现新的连锁区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2818/1866695/3d9af9abdae8/1471-2156-6-S1-S85-1.jpg

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