Sequencing a genome by walking with clone-end sequences: A mathematical analysis
Sequencing a genome by walking with clone-end sequences: A mathematical analysis
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DOI:
10.1101/gr.9.12.1163
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发表时间:
1999-12-01
期刊:
影响因子:
7
通讯作者:
Lander, ES
中科院分区:
文献类型:
--
作者:
Batzoglou, S;Berger, B;Lander, ES
One approach to sequencing a large genome is (1) to sequence a collection of nonoverlapping "seeds" chosen from a genomic library of large-insert clones [such as bacterial artificial chromosomes (BACs)] and then (2) to take successive "walking" steps by selecting and sequencing minimally overlapping clones, using information such as clone-end sequences to identify the overlaps. In this paper we analyze the strategic issues involved in using this approach. We derive formulas showing how two key factors, the initial density of seed clones and the depth of the genomic library used For walking, affect the cost and time of a sequencing project-that is, the amount of redundant sequencing and the number of steps to cover the vast majority of the genome. We also discuss a variant strategy in which a second genomic library with clones having a somewhat smaller insert size is used to close gaps. This approach can dramatically decrease the amount of redundant sequencing, without affecting the rate at which the genome is covered.