Toward accurate high-throughput SNP genotyping in the presence of inherited copy number variation
Toward accurate high-throughput SNP genotyping in the presence of inherited copy number variation
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DOI：
10.1186/1471-2164-8-211
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发表时间：
2007-07-03
期刊：
影响因子：
4.4
通讯作者：
LaFramboise, Thomas
中科院分区：
文献类型：
--
作者：
MacConaill, Laura E.;Aldred, Micheala A.;LaFramboise, Thomas
背景资料：最近发现人类普遍存在拷贝数变异，这迫使人们放弃了在整个常染色体基因组中每个细胞每个位点两个拷贝的假设。特别地，SNP位点不再总是能够准确地分配个体中的三种基因型之一。在拷贝数变异的存在下，理论上个体可能携带两个SNP等位基因中的每一个的任何数量的拷贝。结果：为了解决这个问题，我们已经开发出一种方法来推断一个“广义基因型”从原始SNP微阵列数据。在这里，我们将我们的方法应用于来自48个个体的数据，并发现了数千个异常的SNP，其中大多数位于以前未报告为拷贝数变异的区域。我们表明，我们的等位基因特异性拷贝数遵循孟德尔遗传模式，这将是模糊的SNP等位基因信息的情况下。重复和点突变之间的相互作用，在我们的数据揭示了这些事件在人类历史上的相对频率，表明至少有一些重复事件是recurrent.Conclusion：这种新的多等位基因的SNPs的观点有一个复杂的作用，在疾病关联研究，进一步的工作将是必要的，以准确地评估其重要性。从SNP阵列数据进行广义基因分型的软件可在线免费获得[1]。
Background: The recent discovery of widespread copy number variation in humans has forced a shift away from the assumption of two copies per locus per cell throughout the autosomal genome. In particular, a SNP site can no longer always be accurately assigned one of three genotypes in an individual. In the presence of copy number variability, the individual may theoretically harbor any number of copies of each of the two SNP alleles.Results: To address this issue, we have developed a method to infer a "generalized genotype" from raw SNP microarray data. Here we apply our approach to data from 48 individuals and uncover thousands of aberrant SNPs, most in regions that were previously unreported as copy number variants. We show that our allele-specific copy numbers follow Mendelian inheritance patterns that would be obscured in the absence of SNP allele information. The interplay between duplication and point mutation in our data shed light on the relative frequencies of these events in human history, showing that at least some of the duplication events were recurrent.Conclusion: This new multi-allelic view of SNPs has a complicated role in disease association studies, and further work will be necessary in order to accurately assess its importance. Software to perform generalized genotyping from SNP array data is freely available online [1].