End-sequence profiling: Sequence-based analysis of aberrant genomes

Stanislav Volik, Shaying Zhao, Koei Chin, John H. Brebner, David R. Herndon, Quanzhou Tao, David Kowbel, Guiqing Huang, Anna Lapuk, Wen Lin Kuo, Gregg Magrane, Pieter De Jong, Joe W. Gray, Colin Collins

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


Genome rearrangements are important in evolution, cancer, and other diseases. Precise mapping of the rearrangements is essential for identification of the involved genes, and many techniques have been developed for this purpose. We show here that end-sequence profiling (ESP) is particularly well suited to this purpose. ESP is accomplished by constructing a bacterial artificial chromosome (BAC) library from a test genome, measuring BAC end sequences, and mapping end-sequence pairs onto the normal genome sequence. Plots of BAC end-sequences density identify copy number abnormalities at high resolution. BACs spanning structural aberrations have end pairs that map abnormally far apart on the normal genome sequence. These pairs can then be sequenced to determine the involved genes and breakpoint sequences. ESP analysis of the breast cancer cell line MCF-7 demonstrated its utility for analysis of complex genomes. End sequencing of ≈8,000 clones (0.37-fold haploid genome clonal coverage) produced a comprehensive genome copy number map of the MCF-7 genome at better than 300-kb resolution and identified 381 genome breakpoints, a subset of which was verified by fluorescence in situ hybridization mapping and sequencing.

Original languageEnglish (US)
Pages (from-to)7696-7701
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Jun 24 2003
Externally publishedYes

ASJC Scopus subject areas

  • General


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