Validation of a cost-efficient multi-purpose SNP panel for disease based research.
Validation of a cost-efficient multi-purpose SNP panel for disease based research.
复制标题
DOI：
10.1371/journal.pone.0019699
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bartlett CW
中科院分区：
文献类型：
--
作者：
Hou L;Phillips C;Azaro M;Brzustowicz LM;Bartlett CW
在这里，我们提出了收敛的方法，使用理论计算，经验评估内部和公开的数据集，以及在计算机模拟，验证一组SNP的各种必要的任务，在人类遗传学疾病研究之前，资源致力于对这些样本进行大规模的基因分型研究。虽然大规模资金充足的人类遗传学研究通常具有多达一百万个SNP基因型，但人类遗传学实验室中尚未成为此类研究的一部分的样品可以在试点项目中有效地利用或作为目标后续工作的一部分，尽管此类较小规模的应用需要至少一些全基因组基因型数据用于质量控制目的，例如DNA“条形码”以检测交换或污染问题，确定样本之间的家族关系，并纠正由于人口效应（如试点研究中的人口分层）而产生的偏倚。任何两个给定DNA样品的相对类型分类的经验性能（例如，全同胞、亲本等）表明，对于远交群体，该小组的表现足以对大家族中的关系进行分类，因此也适用于较小的结构，如三胞胎和双胞胎接合性测试。此外，家族关系不会显著降低在谱系中共享SNP基因型的（平均匹配）概率，进一步表明“条形码”的独特性。使用这些SNP进行的非裔美国人病例对照疾病关联研究的模拟表明，即使在复杂的混合样本中，也可以在使用SNP面板的一系列疾病模型下充分校正人群分层。该小组已被验证用于各种人类疾病遗传学研究任务，包括样品条形码，关系验证，群体子结构检测和统计校正。考虑到本文所含的我们的特定测定的基因分型的容易性，该小组代表了人类遗传学家有用且经济的小组。
Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA “barcoding” to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies. Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the “barcode.” Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel. The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists.
登录
查看更多内容
影响因子：
2.7
作者：
Bruse S;Moreau M;Azaro M;Zimmerman R;Brzustowicz L
通讯作者：
Brzustowicz L
影响因子：
5.8
作者：
Wigginton, JE;Abecasis, GR
通讯作者：
Abecasis, GR
影响因子：
2.1
作者：
Amigo, Jorge;Phillips, Christopher;Carracedo, Angel
通讯作者：
Carracedo, Angel
影响因子：
3.1
作者：
Musgrave-Brown, Esther;Ballard, David;Court, Denise Syndercombe
通讯作者：
Court, Denise Syndercombe
影响因子：
2.9
作者：
Sanchez, Juan J.;Phillips, Chris;Morling, Niels
通讯作者：
Morling, Niels