Genome Med. 2009 Jul 3;1(7):66.

Exploring the unknown: assumptions about allelic architecture and strategies for susceptibility variant discovery.

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Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK, and the Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX7 7BN, UK. mark.mccarthy@drl.ox.ac.uk.

Abstract

Identification of common-variant associations for many common disorders has been highly effective, but the loci detected so far typically explain only a small proportion of the genetic predisposition to disease. Extending explained genetic variance is one of the major near-term goals of human genetic research. Next-generation sequencing technologies offer great promise, but optimal strategies for their deployment remain uncertain, not least because we lack a clear view of the characteristics of the variants being sought. Here, I discuss what can and cannot be inferred about complex trait disease architecture from the information currently available and review the implications for future research strategies.

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PMCID: PMC2717392

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Exploring the unknown: assumptions about allelic architecture and strategies for susceptibility variant discovery.

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