The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

The Critical Success of the WTO: Trade Policies of the Current Economic Crisis

This note addresses the trade policy measures states have taken during the current economic crisis and makes comparison with those taken during the Great Depression. While significant protectionist pressures are evident in both crises, the note finds that WTO Members have largely resisted broad protectionist measures and that the further decline in global trade volume during 2009 cannot be attributed to discretionary trade policies. Given these observations, the note suggests four elements of the multilateral trading system that preserve the system's integrity and ensure that the WTO passes its most significant stress test yet. Based on these four elements--economic efficiency, transparency, enforceability, and stability--the note recommends normative principles applicable to all regulation of international economic relations. Oxford University Press 2010, all rights reserved, Oxford University Press.