Vieland Veronica J, Walters Kimberly A, Azaro Marco, Brzustowicz Linda M, Lehner Thomas
Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Hum Hered. 2014;78(1):9-16. doi: 10.1159/000360003. Epub 2014 Jun 21.
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.
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.
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.
Regenotyping older family data can substantially alter the conclusions of linkage analyses.
连锁分析有助于在全基因组序列研究中确定感兴趣的区域。然而，许多连锁研究依赖于较旧的微卫星（MSAT）面板。我们着手确定，如果使用密集的单核苷酸多态性（SNP）图谱对家系进行重新基因分型，结果是否会改变。
我们从美国国立精神卫生研究所储存库和基因组学资源（NRGR）精神分裂症数据储存库中选取了47个西班牙裔美国家庭。我们使用Affymetrix Lat Array对NRGR中所有有可用DNA的个体进行重新基因分型。在优化用于连锁图谱的SNP选择后，我们使用MSAT、SNP和MSAT + SNP图谱比较了信息含量（IC）和连锁结果。
正如预期的那样，在仅使用两个平台都进行基因分型的个体进行的直接“苹果对苹果”比较中，SNP的平均IC（0.78，标准差0.03）高于MSAT（0.51，标准差0.10）；而MSAT + SNP仅提供略高的IC（0.82，标准差0.03）。然而，当利用所有可用个体，包括那些仅在一个平台上有基因型的个体时，与SNP（0.61，标准差0.02）相比，使用MSAT + SNP时IC大幅增加（0.76，标准差0.05）。MSAT和MSAT + SNP之间的连锁结果在峰值的大小、排序和定位方面有明显变化。
对较旧的家系数据进行重新基因分型可显著改变连锁分析的结论。
