Variability in the human genome has far exceeded expectations. In the course of the past three years, we have learned that much of our naturally occurring genetic variation consists of large-scale differences in genome structure, including copy-number variants (CNVs) and balanced rearrangements such as inversions. Recent studies have begun to reveal that structural variants are an important contributor to disease risk; however, structural variants as a class may not conform well to expectations of current methods for gene mapping. New approaches are needed to understand the contribution of structural variants to disease.
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Special thanks to M. Wigler, M.-C. King and D. Levy for helpful discussions and to J. Lupski for his critical reading of the manuscript. My laboratory is funded by the Simons Foundation, Lattner Foundation, Stanley Foundation, the US National Institutes of Health (National Institute of Mental Health, National Human Genome Research Institute), Autism Speaks and the Southwest Autism Research and Resource Center.
The author declares no competing financial interests.
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Sebat, J. Major changes in our DNA lead to major changes in our thinking. Nat Genet 39 (Suppl 7), S3–S5 (2007). https://doi.org/10.1038/ng2095
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