1. Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA
2. Agencourt Bioscience Corporation, Beverly, Massachusetts 01915, USA
3. Division of Medical Genetics, Department of Medicine, and University of Washington Genome Center, University of Washington, Seattle, Washington 98195, USA
4. Agilent Technologies, Santa Clara, California 95051, USA
5. Washington University Genome Sequencing Center, School of Medicine, St Louis, Missouri 63108, USA
6. Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
7. Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA
8. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02114, USA
9. Illumina, Inc., 9885 Towne Centre Drive, San Diego, California 92121, USA

Correspondence to: Evan E. Eichler¹ Correspondence and requests for materials should be addressed to E.E.E. (Email: eee@gs.washington.edu).

Abstract

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale—particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation—a standard for genotyping platforms and a prelude to future individual genome sequencing projects.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.