DNA Copy Number Profiling in Normal and Tumor Genomes
DNA Copy Number Profiling in Normal and Tumor Genomes
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DOI：
10.1007/978-1-84996-196-7_14
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发表时间：
2010-01-01
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影响因子：
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通讯作者：
Zhang, Nancy R.
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作者：
Zhang, Nancy R.
对于生物样品，基因组区域的DNA拷贝数定义为相对于单个对照样品或群体参考样品池，样品基因组内该区域中DNA的拷贝数。在过去的十年中，微阵列技术的显著进步使得能够以高通量的方式对DNA拷贝数进行全基因组范围的精细尺度测量[5，35，39，40，47]。这使得能够进行系统的研究，从而更好地理解DNA拷贝数变化在人类疾病和人类群体表型变异中的作用。这些高通量实验产生了大量结构丰富的数据，激发了新的统计方法的发展。本章回顾了DNA拷贝数数据中出现的计算和统计问题，并调查了它们治疗的最新进展。首先，我们回顾了与DNA拷贝数有关的一些术语和一般概念。拷贝数变异（CNV）是指一个群体中两个或多个个体之间DNA拷贝数不同的基因组区域。到目前为止，已被编目的CNV通常大于1个核糖核酸酶，尽管基于高通量测序[45]和更密集阵列[19]的技术可以检测更短的CNV。在过去的五年中，许多研究[9，10，21，30，41]表明，CNV是人类群体中常见的遗传变异类型，CNV覆盖的基因组比例估计在2%[10]和15%[13]之间。与单核苷酸多态性（SNP）一样，拷贝数变异以孟德尔方式分离并导致表型变异。考虑到它们在碱基对方面覆盖了更多的基因组区域，并且它们比SNP更可能产生有害影响，CNV现在通常与SNP一起用于遗传关联研究。
For a biological sample, the DNA copy number of a genomic region is defined as the number of copies of the DNA in that region within the genome of the sample, relative to either a single control sample or a pool of population reference samples. Within the last decade, significant advances in microarray technology have enabled the genome-wide fine-scale measurement of DNA copy number in a highthroughput manner [5, 35, 39, 40, 47]. This enables systematic studies which can lead to a better understanding of the role of DNA copy number changes in human disease and in phenotypic variation in the human population. These high-throughput experiments produce large amounts of data that are rich in structure, motivating the development of new statistical methods for their analysis. This chapter reviews the computational and statistical problems that arise in DNA copy number data and surveys recent advances in their treatment. First, we review some terms and general concepts relating to DNA copy number. A copy number variant (CNV) is defined as a genomic region where the DNA copy number differs between two or more individuals from a population. CNVs that have so far been catalogued are by convention larger than 1 kilobase, although technologies based on high-throughput sequencing [45] and denser arrays [19] can detect shorter CNVs. Within the last five years, many studies [9, 10, 21, 30, 41] have shown that CNVs are a common type of genetic variation in the human population, with the fraction of the genome covered by CNVs estimated to be between 2%[10] and 15%[13]. Like single nucleotide polymorphisms (SNPs), variants in copy number segregate in a Mendelian fashion and contribute to phenotypic variation. Considering that they cover significantly more genomic territory in terms of base pairs and that they are more likely than SNPs to have a deleterious effect, CNVs are now routinely used alongside SNPs in genetic association studies.