Sequence-based linkage analysis.
Sequence-based linkage analysis.
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DOI：
10.1086/424888
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发表时间：
2004-10
影响因子：
9.8
通讯作者：
Itay Furman;M. Rieder;S. Da Ponte;D. P. Carrington;D. Nickerson;L. Kruglyak;K. Markianos
中科院分区：
文献类型：
--
作者：
Itay Furman;M. Rieder;S. Da Ponte;D. P. Carrington;D. Nickerson;L. Kruglyak;K. Markianos
DNA测序成本的快速下降将使其能够用于新的应用。在这里，我们调查使用DNA测序的同时发现和基因分型的多态性在家庭连锁研究。在所提出的方法中，基因组DNA的短的连续片段，在基因组上有规律地间隔，在每个谱系成员中重新测序，并且在谱系内发现的所有序列多态性被用作遗传标记。我们使用与观察到的人类序列多样性一致的计算机模拟来显示，在整个基因组中以1-2 Mb的间隔的500- 1，000个碱基对的片段提供了等于或超过传统的基于标记的方法的连锁信息。我们通过对CEPH家系中的19号染色体实施基于序列的连锁方法来实验验证这些结果。
The rapid decrease in the cost of DNA sequencing will enable its use for novel applications. Here, we investigate the use of DNA sequencing for simultaneous discovery and genotyping of polymorphisms in family linkage studies. In the proposed approach, short contiguous segments of genomic DNA, regularly spaced across the genome, are resequenced in each pedigree member, and all sequence polymorphisms discovered within a pedigree are used as genetic markers. We use computer simulations consistent with observed human sequence diversity to show that segments of 500-1,000 base pairs, spaced at intervals of 1-2 Mb across the genome, provide linkage information that equals or exceeds that of traditional marker-based approaches. We validate these results experimentally by implementing the sequence-based linkage approach for chromosome 19 in CEPH pedigrees.