Complex and multi-allelic copy number variation in human disease.
Complex and multi-allelic copy number variation in human disease.
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DOI：
10.1093/bfgp/elv028
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发表时间：
2015-09
影响因子：
4
通讯作者：
McCarroll SA
中科院分区：
文献类型：
--
作者：
Usher CL;McCarroll SA
数以百计的拷贝数变异是复杂的和多等位基因的，因为它们具有许多结构等位基因，并且在为当今人类贡献染色体的祖先中多次重排。不仅是这些多等位基因CNVs（mCNVs）的表型的关系通常是未知的，但许多mCNVs还没有被描述在基本水平的等位基因，等位基因频率，结构特征，支持遗传学研究。迄今为止，大多数报道的疾病与这些变体的关联都是通过候选基因研究确定的。然而，只有少数协会已经达到了持久的重复定义的接受水平在许多队列。这可能源于对个体在这些基因座上的等位基因进行精确分子测量的长期挑战。然而，mCNV分析的方法正在迅速改进，mCNV的一些独特特征可能有助于未来的关联研究。它们的各种结构等位基因可能具有不同程度的影响，创造了一个自然的等位基因系列，对表型的影响越来越大，并为研究人员提供了一组关于mCNV的每个等位基因对表型易感程度的自然预测和可检验的假设。此外，mCNVs与单个单核苷酸多态性（SNP）的低至中等相关性可能使其更容易区分mCNVs和附近的SNP作为关联信号的驱动因素，并且可能使初步筛选候选基因座或整个基因组成为可能，以发现许多mCNVs-疾病关系。
Hundreds of copy number variants are complex and multi-allelic, in that they have many structural alleles and have rearranged multiple times in the ancestors who contributed chromosomes to current humans. Not only are the relationships of these multi-allelic CNVs (mCNVs) to phenotypes generally unknown, but many mCNVs have not yet been described at the basic levels—alleles, allele frequencies, structural features—that support genetic investigation. To date, most reported disease associations to these variants have been ascertained through candidate gene studies. However, only a few associations have reached the level of acceptance defined by durable replications in many cohorts. This likely stems from longstanding challenges in making precise molecular measurements of the alleles individuals have at these loci. However, approaches for mCNV analysis are improving quickly, and some of the unique characteristics of mCNVs may assist future association studies. Their various structural alleles are likely to have different magnitudes of effect, creating a natural allelic series of growing phenotypic impact and giving investigators a set of natural predictions and testable hypotheses about the extent to which each allele of an mCNV predisposes to a phenotype. Also, mCNVs’ low-to-modest correlation to individual single-nucleotide polymorphisms (SNPs) may make it easier to distinguish between mCNVs and nearby SNPs as the drivers of an association signal, and perhaps, make it possible to preliminarily screen candidate loci, or the entire genome, for the many mCNV–disease relationships that remain to be discovered.
影响因子：
3.7
作者：
Kulkarni H;Agan BK;Marconi VC;O'Connell RJ;Camargo JF;He W;Delmar J;Phelps KR;Crawford G;Clark RA;Dolan MJ;Ahuja SK
通讯作者：
Ahuja SK