Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays.
Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays.
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DOI：
10.1534/genetics.115.183483
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发表时间：
2016-01
期刊：
影响因子：
3.3
通讯作者：
Kwok PY
中科院分区：
文献类型：
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作者：
Mak AC;Lai YY;Lam ET;Kwok TP;Leung AK;Poon A;Mostovoy Y;Hastie AR;Stedman W;Anantharaman T;Andrews W;Zhou X;Pang AW;Dai H;Chu C;Lin C;Wu JJ;Li CM;Li JW;Yim AK;Chan S;Sibert J;Džakula Ž;Cao H;Yiu SM;Chan TF;Yip KY;Xiao M;Kwok PY
用目前的方法进行全面的全基因组结构变异检测是具有挑战性的。以二倍体细胞为DNA来源，存在大量重复序列，短读DNA测序不能有效地检测结构变异。在这份报告中，我们展示了在纳米通道阵列上成像的长的、荧光标记的DNA分子的基因组图谱可以用于全基因组结构变异的检测，而不需要测序。虽然没有实现全基因组单倍型，但局部阶段化(跨越>；150-kb区域)是常规的，因为来自父母染色体的分子是单独检查的。在一次实验中，我们从1000基因组计划的三人组中生成了基因组图，将这些图与参考人类基因组的图谱进行了比较，并确定了大小为5 kb的结构变异。我们发现，这些人的结构变异比已发表的要多得多，包括一些可能扰乱基因功能或调控的变异。
Comprehensive whole-genome structural variation detection is challenging with current approaches. With diploid cells as DNA source and the presence of numerous repetitive elements, short-read DNA sequencing cannot be used to detect structural variation efficiently. In this report, we show that genome mapping with long, fluorescently labeled DNA molecules imaged on nanochannel arrays can be used for whole-genome structural variation detection without sequencing. While whole-genome haplotyping is not achieved, local phasing (across >150-kb regions) is routine, as molecules from the parental chromosomes are examined separately. In one experiment, we generated genome maps from a trio from the 1000 Genomes Project, compared the maps against that derived from the reference human genome, and identified structural variations that are >5 kb in size. We find that these individuals have many more structural variants than those published, including some with the potential of disrupting gene function or regulation.