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Mutational and selective effects on copy-number variants in the human genome

Nature Genetics volume 39, pages S22–S29 (2007)Cite this article

Abstract

Comprehensive descriptions of large insertion/deletion or segmental duplication polymorphisms (SDs) in the human genome have recently been generated. These annotations, known collectively as structural or copy-number variants (CNVs), include thousands of discrete genomic regions and span hundreds of millions of nucleotides. Here we review the genomic distribution of CNVs, which is strongly correlated with gene, repeat and segmental duplication content. We explore the evolutionary mechanisms giving rise to this nonrandom distribution, considering the available data on both human polymorphisms and the fixed changes that differentiate humans from other species. It is likely that mutational biases, selective effects and interactions between these forces all contribute substantially to the spectrum of human copy-number variation. Although defining these variants with nucleotide-level precision remains a largely unmet but critical challenge, our understanding of their potential medical impact and evolutionary importance is rapidly emerging.

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Figure 1: Copy-number variation along human chromosome 16.
Figure 2: Relationships among copy-number variants, segmental duplications, and genes.
Figure 3: Functional annotation of copy-number variation gene content.
Figure 4: Variation in the X-chromosome opsin locus sequence, structure and resulting phenotype.

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Acknowledgements

The authors acknowledge support from National Human Genome Research Institute Interdisciplinary Training in Genomic Sciences grant T32 HG00035 and National Heart, Lung, and Blood Institute Program for Genomic Applications grant HL066682. E.E.E is an investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Genome Sciences and Evan E. Eichler is also at the Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA. coopergm@u.washington.edu or eee@gs.washington.edu,

    Gregory M Cooper, Deborah A Nickerson & Evan E Eichler

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Supplementary information

Supplementary Table 1

Human genomic intervals annotated to be part of a copy-number variant (XLS 295 kb)

Supplementary Table 2

Densities of copy-number variants and other genomic features in 1-Mb non-overlapping windows (XLS 487 kb)

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Cooper, G., Nickerson, D. & Eichler, E. Mutational and selective effects on copy-number variants in the human genome. Nat Genet 39 (Suppl 7), S22–S29 (2007). https://doi.org/10.1038/ng2054

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