Breakpoint characterization of large deletions in EXT1 or EXT2 in 10 Multiple Osteochondromas families

<p>Abstract</p> <p>Background</p> <p>Osteochondromas (cartilage-capped bone tumors) are by far the most commonly treated of all primary benign bone tumors (50%). In 15% of cases, these tumors occur in the context of a hereditary syndrome called multiple osteochondromas (MO), an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped bone tumors at children's metaphyses. MO is caused by various mutations in <it>EXT1 </it>or <it>EXT2</it>, whereby large genomic deletions (single-or multi-exonic) are responsible for up to 8% of MO-cases.</p> <p>Methods</p> <p>Here we report on the first molecular characterization of ten large <it>EXT1</it>- and <it>EXT2</it>-deletions in MO-patients. Deletions were initially indentified using MLPA or FISH analysis and were subsequently characterized using an MO-specific tiling path array, allele-specific PCR-amplification and sequencing analysis.</p> <p>Results</p> <p>Within the set of ten large deletions, the deleted regions ranged from 2.7 to 260 kb. One <it>EXT2 </it>exon 8 deletion was found to be recurrent. All breakpoints were located outside the coding exons of <it>EXT1 </it>and <it>EXT2</it>. Non-allelic homologous recombination (NAHR) mediated by <it>Alu</it>-sequences, microhomology mediated replication dependent recombination (MMRDR) and non-homologous end-joining (NHEJ) were hypothesized as the causal mechanisms in different deletions.</p> <p>Conclusions</p> <p>Molecular characterization of <it>EXT1</it>- and <it>EXT2</it>-deletion breakpoints in MO-patients indicates that NAHR between <it>Alu-</it>sequences as well as NHEJ are causal and that the majority of these deletions are nonrecurring. These observations emphasize once more the huge genetic variability which is characteristic for MO. To our knowledge, this is the first study characterizing large genomic deletions in <it>EXT1 </it>and <it>EXT2</it>.</p

Arbeitsmarkt und Demographie

Im vorliegenden Beitrag werden die wechselseitigen Beziehungen von demographischen Veränderungen und Arbeitsmarktentwicklungen anhand eines Literaturüberblicks diskutiert. Insbesondere werden die Effekte von demographischen Strukturen und Prozessen auf die Lohnstruktur und auf die Arbeitslosigkeit präsentiert, wobei sowohl Mikro- als auch Makroansätze diskutiert und die Implikationen der Bevölkerungsalterung für den Arbeitsmarkt besprochen werden. In Mikroansätzen werden z.B. altersspezifische Profile der Humankapitalbildung als optimale Lösung eines individuellen Entscheidungsproblems modelliert. Im Gegensatz dazu werden in Makroansätzen die Beziehung von Makrovariablen, z.B. Jugendarbeitslosigkeit und Besetzungsstärke der eigenen Kohorte, modelliert. Schließlich stellen wir verschiedene theoretische Perspektiven vor, welche Effekte arbeitsmarktrelevanter Faktoren auf die Fertilität untersuchen

The Role of Environmental and Technology Policies in the Transition to a Low-Carbon Energy Industry

In a dynamic general equilibrium model we study the interplay between gradual and structural change in the transition to a low-carbon energy industry. We focus on the welfare-theoretic consequences of diverging social and private rates of time preference and a time-to-build feature in capital accumulation. Both features are particularly important in the transformation of energy systems. We show that only a combination of environmental and technology policies can achieve a socially optimal transition. We thus provide a new reason for environmental regulation to be complemented by technology policy such as a non-distortionary investment subsidy

'NIEKATH' Kathetersystem fuer die Nierenbeckendrucksensorik - Konzept und Mustererstellng eines Sensorkatheters fuer Nierenbecken Schlussbericht

SIGLEAvailable from TIB Hannover: F01B9+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman