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The resequencing imperative

Nature Genetics volume 39, pages 439–440 (2007)Cite this article

The possibility of deep population resequencing of genes has generated excitement over its potentially promising role in understanding complex human traits. A new study has now demonstrated the utility of this approach, reporting the resequencing of a lipid metabolism gene in a large multiethnic population and definitively showing that coding variants in the gene are associated with plasma triglyceride levels.

Understanding the genetic architecture of heritable complex (multigene) traits is of great interest to the biomedical community. The genetic factors contributing to these complex traits are presumed to be a combination of common sequence variants (≥5% frequency), each of which has a small effect, and rare sequence variants (≤5% frequency), each of which has a large effect in the individuals carrying them. Recently, there have been a few major advances in identifying common disease-associated variants by genome-wide association studies that genotype hundreds of thousands of SNPs that 'tag' most of the other common variants in humans. Although the high costs of conventional sequencing have limited systematic searches for rare variants contributing to complex trait variation, as they entail determining a gene's nucleotide sequence in thousands of individuals, recent advances in sequencing technologies have rapidly reduced costs1 and have put such large-scale population-based studies within reach.

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  1. Eric J. Topol and Kelly A. Frazer are at Scripps Genomic Medicine, Scripps Health and The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. etopol@scripps.edu or kfrazer@scripps.edu

    Eric J Topol & Kelly A Frazer

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  1. Eric J Topol
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  2. Kelly A Frazer
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The authors declare no competing financial interests.

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Topol, E., Frazer, K. The resequencing imperative. Nat Genet 39, 439–440 (2007). https://doi.org/10.1038/ng0407-439

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