A capacity and value based model for data architectures adopting integration technologies

The paper discusses two concepts that have been associated with various approaches to data and information, namelycapacity and value, focusing on data base architectures, and on two types of technologies diffusely used in integrationprojects, namely data integration, in the area of Enterprise Information Integration, and publish & subscribe, in the area ofEnterprise Application Integration. Furthermore, the paper proposes and discusses a unifying model for information capacityand value, that considers also quality constraints and run time costs of the data base architecture

Great ape Y Chromosome and mitochondrial DNA phylogenies reflect subspecies structure and patterns of mating and dispersal

The distribution of genetic diversity in great ape species is likely to have been affected by patterns of dispersal and mating. This has previously been investigated by sequencing autosomal and mitochondrial DNA (mtDNA), but large-scale sequence analysis of the male-specific region of the Y Chromosome (MSY) has not yet been undertaken. Here, we use the human MSY reference sequenceas a basis for sequence capture and read mapping in 19 great ape males, combining the data with sequences extracted from the published whole genomes of 24 additional males to yield a total sample of 19 chimpanzees, four bonobos, 14 gorillas, and six orangutans, in which interpretable MSY sequence ranges from 2.61 to 3.80 Mb. This analysis reveals thousands of novel MSY variants and defines unbiased phylogenies. We compare these with mtDNA-based trees in the same individuals, estimating time-to-most-recent common ancestor (TMRCA) for key nodes in both cases. The two loci show high topological concordance and are consistent with accepted (sub)species definitions, but time depths differ enormously between loci and (sub)species, likely reflecting different dispersal and mating patterns. Gorillas and chimpanzees/bonobos present generally low and high MSY diversity, respectively, reflecting polygyny versus multimale-multifemale mating. However, particularly marked differences exist among chimpanzee subspecies: The western chimpanzee MSY phylogeny has a TMRCA of only 13.2 (10.8-15.8) thousand years, but that for central chimpanzees exceeds 1 million years. Cross-species comparison within a single MSY phylogeny emphasizes the low human diversity, and reveals speciesspecific branch length variation that may reflect differences in long-term generation times

Molecular Anthropology in the genomic era

Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have passed since the symposium ''Classification and Human Evolution'' ( 1962, Burg Wartenstein, Austria), where the term was formally introduced by Emil Zuckerkandl. In this time, Molecular Anthropology has developed both methodologically and theoretically and extended its applications, so covering key aspects of human evolution such as the reconstruction of the history of human populations and peopling processes, the characterization of DNA in extinct humans and the role of adaptive processes in shaping the genetic diversity of our species. In the current scientific panorama, molecular anthropologists have to face a double challenge. As members of the anthropological community, we are strongly committed to the integration of biological findings and other lines of evidence (e.g. linguistic and archaeological), while keeping in line with methodological innovations which are moving the approach from the genetic to the genomic level. In this framework, the meeting "DNA Polymorphisms in Human Populations: Molecular Anthropology in the Genomic Era" ( Rome, December 3-5, 2009) offered an opportunity for discussion among scholars from different disciplines, while paying attention to the impact of recent methodological innovations. Here we present an overview of the meeting and discuss perspectives and prospects of Molecular Anthropology in the genomic era

Insights into the demographic history of african pygmies from complete mitochondrial genomes

Pygmy populations are among the few hunter-gatherers currently living in sub-Saharan Africa and are mainly represented by two groups, Eastern and Western, according to their current geographical distribution. They are scattered across the Central African belt and surrounded by Bantu-speaking farmers, with whom they have complex social and economic interactions. To investigate the demographic history of Pygmy groups, a population approach was applied to the analysis of 205 complete mitochondrial DNA (mtDNA) sequences from ten central African populations. No sharing of maternal lineages was observed between the two Pygmy groups, with haplogroup L1c being characteristic of the Western group but most of Eastern Pygmy lineages falling into subclades of L0a, L2a, and L5. Demographic inferences based on Bayesian coalescent simulations point to an early split among the maternal ancestors of Pygmies and those of Bantu-speaking farmers (similar to 70,000 years ago [ya]). Evidence for population growth in the ancestors of Bantu-speaking farmers has been observed, starting similar to 65,000 ya, well before the diffusion of Bantu languages. Subsequently, the effective population size of the ancestors of Pygmies remained constant over time and similar to 27,000 ya, coincident with the Last Glacial Maximum, Eastern and Western Pygmies diverged, with evidence of subsequent migration only among the Western group and the Bantu-speaking farmers. Western Pygmies show signs of a recent bottleneck 4,000-650 ya, coincident with the diffusion of Bantu Languages, whereas Eastern Pygmies seem to have experienced a more ancient decrease in population size (20,000-4,000 ya). In conclusion, the results of this first attempt at analyzing complete mtDNA sequences at the population level in sub-Saharan Africa not only support previous findings but also offer new insights into the demographic history of Pygmy populations, shedding new light on the ancient peopling of the African continent.Direccion General de Investigacion, Ministerio de Educacion y Ciencia, Spain [CGL2007-61016]; Direccio General de Recerca, Generalitat de Catalunya [2009SGR1101]info:eu-repo/semantics/publishedVersio

Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK

Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1.3 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe. We performed a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at P-value < 5 × 10-6, four being monomorphic or rare in European populations. Gene prioritisation strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of analysing underrepresented populations in genetic epidemiology, and the urgent need for larger genomic studies to boost discovery power to better understand smoking behaviours, as well as many other traits

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution of Genes and Pathways Influencing Lung Function and Chronic Obstructive Pulmonary Disease Risk

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies

Subdividing Y-chromosome haplogroup R1a1 reveals Norse Viking dispersal lineages in Britain

The influence of Viking-Age migrants to the British Isles is obvious in archaeological and place-names evidence, but their demographic impact has been unclear. Autosomal genetic analyses support Norse Viking contributions to parts of Britain, but show no signal corresponding to the Danelaw, the region under Scandinavian administrative control from the ninth to eleventh centuries. Y-chromosome haplogroup R1a1 has been considered as a possible marker for Viking migrations because of its high frequency in peninsular Scandinavia (Norway and Sweden). Here we select ten Y-SNPs to discriminate informatively among hg R1a1 sub-haplogroups in Europe, analyse these in 619 hg R1a1 Y chromosomes including 163 from the British Isles, and also type 23 short-tandem repeats (Y-STRs) to assess internal diversity. We find three specifically Western-European sub-haplogroups, two of which predominate in Norway and Sweden, and are also found in Britain; starlike features in the STR networks of these lineages indicate histories of expansion. We ask whether geographical distributions of hg R1a1 overall, and of the two sub-lineages in particular, correlate with regions of Scandinavian influence within Britain. Neither shows any frequency difference between regions that have higher (≥10%) or lower autosomal contributions from Norway and Sweden, but both are significantly overrepresented in the region corresponding to the Danelaw. These differences between autosomal and Y-chromosomal histories suggest either male-specific contribution, or the influence of patrilocality. Comparison of modern DNA with recently available ancient DNA data supports the interpretation that two sub-lineages of hg R1a1 spread with the Vikings from peninsular Scandinavia

The Y-Chromosome Tree Bursts into Leaf: 13,000 High-Confidence SNPs Covering the Majority of Known Clades

Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51x, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analyzing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of nonsynonymous variants in 15 MSY single-copy genes

Signatures of the Preagricultural Peopling Processes in Sub-Saharan Africa as Revealed by the Phylogeography of Early Y Chromosome Lineages

Abstract The study of Y chromosome variation has helped reconstruct demographic events associated with the spread of languages, agriculture, and pastoralism in sub-Saharan Africa, but little attention has been given to the early history of the continent. In order to overcome this lack of knowledge, we carried out a phylogeographic analysis of haplogroups A and B in a broad data set of sub-Saharan populations. These two lineages are particularly suitable for this objective because they are the two most deeply rooted branches of the Y chromosome genealogy. Their distribution is almost exclusively restricted to sub-Saharan Africa where their frequency peaks at 65% in groups of foragers. The combined high-resolution single nucleotide polymorphism analysis with short tandem repeats variation of their subclades reveals strong geographic and population structure for both haplogroups. This has allowed us to identify specific lineages related to regional preagricultural dynamics in different areas of sub-Saharan Africa. In addition, we observed signatures of relatively recent contact, both among Pygmies and between them and Khoisan speaker groups from southern Africa, thus contributing to the understanding of the complex evolutionary relationships among African hunter-gatherers. Finally, by revising the phylogeography of the very early human Y chromosome lineages, we have obtained support for the role of southern Africa as a sink, rather than a source, of the first migrations of modern humans from eastern and central parts of the continent. These results open new perspectives on the early history of Homo sapiens in Africa, with particular attention to areas of the continent where human fossil remains and archaeological data are scant