An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery.

Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs

The Laws of Deuteronomy

London277 p.; 21 c

Women, Law, and the Genesis traditions

Edinburgh110 p.; 20 c

Economic conditions and the popularity of the incumbent party in canada

If the country had been as prosperous as it should have been, or as prosperous as it is represented to be, a good deal of discontent which now prevails would have been alleviated; for political causes alone seldom produce serious discontent, unless they affect injuriously the economic condition of the people

Shifts in the indicators used by the monetary authorities in Canada

This study estimates a single-equation reaction function to represent shifts in the economic indicators to which the Bank of Canada has responded in setting short-term interest rates during the period of flexible exchange rates since 1970. Over this period, the major indicators appear to have been, in succession, changes in the unemployment rate, the growth rate of the money supply, changes in American interest rates, and changes in the utilization of industrial capacity. Such results suggest that macroeconomic models of the Canadian economy could be subject to specification error if they assume that the Bank's response to indicators does not change over time

The control of export credit subsidies and its welfare consequences

A two-stage Bertrand duopoly model demonstrates how the sequence of firm and government actions can explain the origins of export credit subsidies, and can affect the welfare consequences of international agreements to adopt subsidy rate ceilings. Firms act first by stating prices in applications for export credit, and can induce positive subsidies by inflating the prices. The subsidies transfer rents from governments to firms without changing welfare, defined as profits less subsidy expenditures. Governments become the first to act by adopting subsidy rate ceilings that bind. Ceilings cause firms to lower prices, such that if a positive ceiling binds, welfare falls