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

The value of regenotyping older linkage data sets with denser marker panels.
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DOI:
10.1159/000360003
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发表时间:
2014
期刊:
影响因子:
1.8
通讯作者:
Lehner T
Lehner T
中科院分区:
生物学4区
文献类型:
--
作者:
Vieland VJ;Walters KA;Azaro M;Brzustowicz LM;Lehner T

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连锁分析可以帮助确定全基因组序列研究中感兴趣的区域。然而,许多关联研究依赖于较旧的微卫星(MSAT)面板。我们着手确定如果我们使用密集的SNP图谱对家族进行基因分型,结果是否会改变。我们从NIMH和基因组学资源(NRGR)精神分裂症数据库中选择了47个西班牙裔美国家庭。我们对所有个体进行了基因分型,这些个体的DNA可从Affysself Lat阵列上的NRGR获得。在优化SNP选择以包含在连锁图上之后,我们比较了使用MSAT、SNP和MSAT+SNP图的信息含量(IC)和连锁结果。正如预期的那样,SNP提供更高的平均IC(0.78,s.d. 0.03)比MSAT(0.51,s.d. 0.10),在仅使用两个平台上基因分型的个体的直接“苹果对苹果”比较中;而MSAT+SNP仅提供略高的IC(0.82,s.d. 0.03)。然而,当利用所有可用个体时,包括仅在一个平台上具有可用基因型的那些个体,使用MSAT+SNP(0.76,s.d. 0.05)与SNP(0.61,s.d. 0.02)。MSAT和MSAT+SNP之间的连锁结果在幅度、等级排序和峰的定位方面发生了明显变化。对较老的家族数据进行基因分型可以大大改变连锁分析的结论。
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 higher average IC (0.78, s.d. 0.03) than MSAT (0.51, s.d. 0.10), in a direct “apples-to-apples” comparison using only individuals genotyped on both platforms; while MSAT+SNP provided only slightly higher IC (0.82, s.d. 0.03). However, when utilizing all available individuals, including those who had available genotypes on only one platform, IC was substantially increased using MSAT+SNP (0.76, s.d. 0.05) compared to SNP (0.61, s.d. 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.
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