Detection of large-scale variation in the human genome
A John Iafrate1, 2, Lars Feuk3, Miguel N Rivera1, 2, Marc L Listewnik1, Patricia K Donahoe2, 4, Ying Qi3, Stephen W Scherer3, 5 & Charles Lee1, 2, 5
1 Department of Pathology, Brigham and Women's Hospital, 20 Shattuck St., Thorn 6-28, Boston, Massachusetts 02115, USA.

2 Harvard Medical School, Boston, Massachusetts 02115, USA.

3 Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; and Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada.

4 Department of Surgery and Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

5 These authors contributed equally to this work.

Correspondence should be addressed to Charles Lee clee@rics.bwh.harvard.edu


We identified 255 loci across the human genome that contain genomic imbalances among unrelated individuals. Twenty-four variants are present in > 10% of the individuals that we examined. Half of these regions overlap with genes, and many coincide with segmental duplications or gaps in the human genome assembly. This previously unappreciated heterogeneity may underlie certain human phenotypic variation and susceptibility to disease and argues for a more dynamic human genome structure.