Genome assembly comparison identifies structural variants in the human genome

Razi Khaja, Junjun Zhang, Jeffrey R. MacDonald, Yongshu He, Ann M. Joseph-George, John Wei, Muhammad A. Rafiq, Cheng Qian, Mary Shago, Lorena Pantano, Hiroyuki Aburatani, Keith Jones, Richard Redon, Matthew Hurles, Lluis Armengol, Xavier P. Estivill, Richard J. Mural, Charles Lee, Stephen W. Scherer, Lars Feuk

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131 Citations (Scopus)


Numerous types of DNA variation exist, ranging from SNPs to larger structural alterations such as copy number variants (CNVs) and inversions. Alignment of DNA sequence from different sources has been used to identify SNPs and intermediate-sized variants (ISVs). However, only a small proportion of total heterogeneity is characterized, and little is known of the characteristics of most smaller-sized (<50 kb) variants. Here we show that genome assembly comparison is a robust approach for identification of all classes of genetic variation. Through comparison of two human assemblies (Celera's R27c compilation and the Build 35 reference sequence), we identified megabases of sequence (in the form of 13,534 putative non-SNP events) that were absent, inverted or polymorphic in one assembly. Database comparison and laboratory experimentation further demonstrated overlap or validation for 240 variable regions and confirmed >1.5 million SNPs. Some differences were simple insertions and deletions, but in regions containing CNVs, segmental duplication and repetitive DNA, they were more complex. Our results uncover substantial undescribed variation in humans, highlighting the need for comprehensive annotation strategies to fully interpret genome scanning and personalized sequencing projects.

Original languageEnglish
Pages (from-to)1413-1418
Number of pages6
JournalNature Genetics
Issue number12
Publication statusPublished - 5 Dec 2006
Externally publishedYes


ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Khaja, R., Zhang, J., MacDonald, J. R., He, Y., Joseph-George, A. M., Wei, J., Rafiq, M. A., Qian, C., Shago, M., Pantano, L., Aburatani, H., Jones, K., Redon, R., Hurles, M., Armengol, L., Estivill, X. P., Mural, R. J., Lee, C., Scherer, S. W., & Feuk, L. (2006). Genome assembly comparison identifies structural variants in the human genome. Nature Genetics, 38(12), 1413-1418.