29 research outputs found
Multiple Local and Recent Founder Effects of TGM1 in Spanish Families
<div><h3>Background</h3><p>Mutations in the <em>TGM1</em> gene encoding transglutaminase 1 are a major cause of autosomal recessive congenital ichthyosis. In the Galician (NW Spain) population, three mutations, c.2278C>T, c.1223_1227delACAC and c.984+1G>A, were observed at high frequency, representing ∼46%, ∼21% and ∼13% of all <em>TGM1</em> gene mutations, respectively. Moreover, these mutations were reported only once outside of Galicia, pointing to the existence of historical episodes of local severe genetic drift in this region.</p> <h3>Methodology/Principal Findings</h3><p>In order to determine whether these mutations were inherited from a common ancestor in the Galician population, and to estimate the number of generations since their initial appearance, we carried out a haplotype-based analysis by way of genotyping 21 SNPs within and flanking the <em>TGM1</em> gene and 10 flanking polymorphic microsatellite markers spanning a region of 12 Mb. Two linkage disequilibrium based methods were used to estimate the time to the most recent common ancestor (TMRCA), while a Bayesian-based procedure was used to estimate the age of the two mutations. Haplotype reconstruction from unphased genotypes of all members of the affected pedigrees indicated that all carriers for each of the two mutations harbored the same haplotypes, indicating common ancestry.</p> <h3>Conclusions/Significance</h3><p>In good agreement with the documentation record and the census, both mutations arose between 2,800–2,900 years ago (y.a.), but their TMRCA was in the range 600–1,290 y.a., pointing to the existence of historical bottlenecks in the region followed by population growth. This demographic scenario finds further support on a Bayesian Coalescent Analysis based on <em>TGM1</em> haplotypes that allowed estimating the occurrence of a dramatic reduction of effective population size around 900–4,500 y.a. (95% highest posterior density) followed by exponential growth.</p> </div
Medium-size-vessel vasculitis
Medium-size-artery vasculitides do occur in childhood and manifest, in the main, as polyarteritis nodosa (PAN), cutaneous PAN and Kawasaki disease. Of these, PAN is the most serious, with high morbidity and not inconsequential mortality rates. New classification criteria for PAN have been validated that will have value in epidemiological studies and clinical trials. Renal involvement is common and recent therapeutic advances may result in improved treatment options. Cutaneous PAN is a milder disease characterised by periodic exacerbations and often associated with streptococcal infection. There is controversy as to whether this is a separate entity or part of the systemic PAN spectrum. Kawasaki disease is an acute self-limiting systemic vasculitis, the second commonest vasculitis in childhood and the commonest cause of childhood-acquired heart disease. Renal manifestations occur and include tubulointerstitial nephritis and renal failure. An infectious trigger and a genetic predisposition seem likely. Intravenous immunoglobulin (IV-Ig) and aspirin are effective therapeutically, but in resistant cases, either steroid or infliximab have a role. Greater understanding of the pathogenetic mechanisms involved in these three types of vasculitis and better long-term follow-up data will lead to improved therapy and prediction of prognosis
Patent rights, product market reforms, and innovation
In this paper, we provide empirical evidence to the effect that strong patent rights may complement competition-increasing product market reforms in fostering innovation. First, we find that the product market reform induced by the large-scale internal market reform of the European Union in 1992 enhanced, on average, innovative investments in manufacturing industries of countries with strong patent rights since the pre-sample period, but not so in industries of countries with weaker patent rights. Second, the positive response to the product market reform is more pronounced in industries where, in general, innovators tend to value patent protection higher than in other industries, except for the manufacture of electrical and optical equipment. The observed complementarity between competition and patent protection can be rationalized using a Schumpeterian growth model with step-by-step innovation. In such a model, better patent protection prolongs the period over which a firm that successfully escapes competition by innovating, actually enjoys higher monopoly rents from its technological upgrade.Economic
Economic Systems of Developing Nations
This essay employs a database of covering 31 different types of economic institutions for 41 developing nations. Defining an economic system in terms of clusters of complementary institutions and performing a cluster analysis, I derive four different types of economic systems. Then I explore the impact of the economic system on the economic growth, inflation rate, and production volatility of the nations with each system. Comparative Economic Studies (2006) 48, 77–99. doi:10.1057/palgrave.ces.8100072