Fine-scale structural variation of the human genome

Nat Genet. 2005 Jul;37(7):727-32. doi: 10.1038/ng1562. Epub 2005 May 15.


Inversions, deletions and insertions are important mediators of disease and disease susceptibility. We systematically compared the human genome reference sequence with a second genome (represented by fosmid paired-end sequences) to detect intermediate-sized structural variants >8 kb in length. We identified 297 sites of structural variation: 139 insertions, 102 deletions and 56 inversion breakpoints. Using combined literature, sequence and experimental analyses, we validated 112 of the structural variants, including several that are of biomedical relevance. These data provide a fine-scale structural variation map of the human genome and the requisite sequence precision for subsequent genetic studies of human disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Pairing
  • Cell Line, Tumor
  • Computational Biology
  • Genome, Human*
  • Genomic Instability*
  • Humans
  • Mutation*
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Genetic*
  • Reference Values
  • Sequence Analysis, DNA