Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Finding revelation in anthropology: Alexander Winchell, William Robertson Smith and the heretical imperative

Anthropological inquiry has often been considered an agent of intellectual secularization. Not least is this so in the sphere of religion, where anthropological accounts have often been taken to represent the triumph of naturalism. This metanarrative however fails to recognise that naturalistic explanations could sometimes be espoused for religious purposes and in defence of confessional creeds. This essay examines two late nineteenth-century figures – Alexander Winchell in the United States, and William Robertson Smith in Britain – who found in anthropological analysis resources to bolster rather than undermine faith. In both cases these individuals found themselves on the receiving end of ecclesiastical censure and were dismissed from their positions at church-governed institutions. But their motivation was to vindicate divine revelation, in Winchell’s case from the physical anthropology of human origins and in Smith’s from the cultural anthropology of Semitic ritual.

Using Modern Tools to Explain the Use of the Smith Chart

The concept of explaining the use of an old tool like the Smith chart, using modern tools like MATLAB [1] scripts in combination with e-learning facilities, is exemplified by two MATLAB scripts. These display, step by step, the graphical procedure that must be used to solve the double-stub impedance-matching problem. These two scripts correspond to two different possible ways to analyze this matching problem, and they are important for students to learn by themselves.

Literature, translation and national identity: Christina Rossetti and Rosalía de Castro in the work of Plácido Castro

Plácido Castro‘s work has aroused our interest, because it evolves around the question of Galician personality and identity. While working as a journalist and a translator or while writing essays on different literary issues, Plácido Castro has never forgotten his roots or his nation. One could even say that his whole life turns around Galicia. Our purpose is to make a critical analysis of his work, especially as a translator, and try to show how he used translation in order to develop national conscience and identity and to see how far his ideology interfered in the interpretation and translation of Rossetti‘s poetry, in which he found a great similarity with Rosalìa de Castro‘s work.

How do current term structure model behave beyond the last liquid point?: A comparison of the DNS and Smith-Wilson methods

A Work Project, presented as part of the requirements for the Award of a Master’s Double Degree in Finance from Maastricht University and NOVA – School of Business and Economics

Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.

A large fraction of genome variation between individuals is comprised of submicroscopic copy number variation of genomic DNA segments. We assessed the relative contribution of structural changes and gene dosage alterations on phenotypic outcomes with mouse models of Smith-Magenis and Potocki-Lupski syndromes. We phenotyped mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+), and balanced 2n compound heterozygous (Deletion/Duplication) copies of the same region. Parallel to the observations made in humans, such variation in gene copy number was sufficient to generate phenotypic consequences: in a number of cases diametrically opposing phenotypes were associated with gain versus loss of gene content. Surprisingly, some neurobehavioral traits were not rescued by restoration of the normal gene copy number. Transcriptome profiling showed that a highly significant propensity of transcriptional changes map to the engineered interval in the five assessed tissues. A statistically significant overrepresentation of the genes mapping to the entire length of the engineered chromosome was also found in the top-ranked differentially expressed genes in the mice containing rearranged chromosomes, regardless of the nature of the rearrangement, an observation robust across different cell lineages of the central nervous system. Our data indicate that a structural change at a given position of the human genome may affect not only locus and adjacent gene expression but also "genome regulation." Furthermore, structural change can cause the same perturbation in particular pathways regardless of gene dosage. Thus, the presence of a genomic structural change, as well as gene dosage imbalance, contributes to the ultimate phenotype.

Savolax lähn : Sysmä, Hardola, Hirvensalmi, St Michels, Jockas, Sulkava, Menduharju, Christina, Pumala socknar och capeller

1 kartta : käsinpiirros, vär. ; 56,5 x 103 cm. Kuvailu kääntöpuolelta. Mittakaava laskettu janamittakaavasta. Kankaalle liimattu.

[Le capitaine Charles A.] Smith commandant [le paquebot] Imperator CN [Central News Photo Service] New-York : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58713

Mr Charles Smith, membre honoraire de la faculté du collège américain à Constantinople : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59806

Miss Eleanor and miss Ruth [Smith, les 2 soeurs nageuses américaines] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59281

Miss Eleanor and Miss Ruth [Smith, les 2 soeurs nageuses américaines] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 59282

Herramienta. Caso Smith Shoes

Desarrollo empresarial y creación de empresa