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The value of regenotyping older linkage data sets with denser marker panels

机译:使用更密集的标记面板重新定型较早的链接数据集的价值

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Objectives: Linkage analysis can help determine regions of interest in whole-genome sequence studies. However, many linkage studies rely on older microsatellite (MSAT) panels. We set out to determine whether results would change if we regenotyped families using a dense map of SNPs. Methods: We selected 47 Hispanic-American families from the NIMH Repository and Genomics Resource (NRGR) schizophrenia data repository. We regenotyped all individuals with DNA available from the NRGR on the Affymetrix Lat Array. After optimizing SNP selection for inclusion on the linkage map, we compared information content (IC) and linkage results using MSAT, SNP and MSAT+SNP maps. Results: As expected, SNP provided a higher average IC (0.78, SD 0.03) than MSAT (0.51, SD 0.10) in a direct 'apples-to-apples' comparison using only individuals genotyped on both platforms; while MSAT+SNP provided only a slightly higher IC (0.82, SD 0.03). However, when utilizing all available individuals, including those who had genotypes available on only one platform, the IC was substantially increased using MSAT+SNP (0.76, SD 0.05) compared to SNP (0.61, SD 0.02). Linkage results changed appreciably between MSAT and MSAT+SNP in terms of magnitude, rank ordering and localization of peaks. Conclusions: Regenotyping older family data can substantially alter the conclusions of linkage analyses.
机译:目标:连锁分析可以帮助确定全基因组序列研究中的目标区域。但是,许多链接研究依赖于较旧的微卫星(MSAT)面板。我们着手确定如果使用密集的SNP图谱重新命名家族,结果是否会改变。方法:我们从NIMH知识库和基因组资源(NRGR)精神分裂症数据库中选择了47个西班牙裔美国人家庭。我们使用可从Affymetrix Lat Array上的NRGR获得的DNA对所有个体进行了重新定型。在优化SNP选择以包含在链接图上之后,我们使用MSAT,SNP和MSAT + SNP图比较了信息内容(IC)和链接结果。结果:正如预期的那样,在仅使用两个平台上进行基因分型的个体进行的直接“对苹果”比较中,SNP的平均IC(0.78,SD 0.03)比MSAT(0.51,SD 0.10)高。而MSAT + SNP仅提供稍高的IC(0.82,SD 0.03)。但是,当利用所有可用个体,包括仅在一个平台上具有基因型的个体时,与SNP(0.61,SD 0.02)相比,使用MSAT + SNP(0.76,SD 0.05)大大提高了IC。 MSAT和MSAT + SNP之间的链接结果在幅度,等级排序和峰的位置方面均发生了明显变化。结论:对较老的家庭数据进行重新定型可以大大改变连锁分析的结论。

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