University of Copenhagen

About: University of Copenhagen is a education organization based out in Copenhagen, Denmark. It is known for research contribution in the topics: Population & Galaxy. The organization has 57645 authors who have published 149740 publications receiving 5903093 citations. The organization is also known as: Copenhagen University & Københavns Universitet.

Assessing the Evolutionary Impact of Amino Acid Mutations in the Human Genome

Abstract: Quantifying the distribution of fitness effects among newly arising mutations in the human genome is key to resolving important debates in medical and evolutionary genetics. Here, we present a method for inferring this distribution using Single Nucleotide Polymorphism (SNP) data from a population with non-stationary demographic history (such as that of modern humans). Application of our method to 47,576 coding SNPs found by direct resequencing of 11,404 protein coding-genes in 35 individuals (20 European Americans and 15 African Americans) allows us to assess the relative contribution of demographic and selective effects to patterning amino acid variation in the human genome. We find evidence of an ancient population expansion in the sample with African ancestry and a relatively recent bottleneck in the sample with European ancestry. After accounting for these demographic effects, we find strong evidence for great variability in the selective effects of new amino acid replacing mutations. In both populations, the patterns of variation are consistent with a leptokurtic distribution of selection coefficients (e.g., gamma or log-normal) peaked near neutrality. Specifically, we predict 27–29% of amino acid changing (nonsynonymous) mutations are neutral or nearly neutral (|s| 1%). Our results are consistent with 10–20% of amino acid differences between humans and chimpanzees having been fixed by positive selection with the remainder of differences being neutral or nearly neutral. Our analysis also predicts that many of the alleles identified via whole-genome association mapping may be selectively neutral or (formerly) positively selected, implying that deleterious genetic variation affecting disease phenotype may be missed by this widely used approach for mapping genes underlying complex traits.

Draft genome of the wheat A-genome progenitor Triticum urartu

Abstract: The genome sequence and its analysis of the diploid wild wheat Triticum urartu (progenitor of the wheat A genome) represent a tool for studying the complex, polyploid wheat genomes and should be a valuable resource for the genetic improvement of wheat. The hexaploid genome of bread wheat Triticum aestivum, designated AABBDD, evolved as a result of hybridization between three ancestral grasses. Two papers published in the issue of Nature present genome sequences and analysis of two of these wheat progenitors. First, the genome sequence of the diploid wild wheat T. urartu (ancestor of the A genome), which resembles cultivated wheat more strongly than either Aegilops speltoides (the B ancestor) or Ae. tauschii (the D donor). And second, the Ae. tauschii genome, together with an analysis of its transcriptome. These genomes and their analyses will be powerful tools for the study of complex, polyploid wheat genomes and a valuable resource for genetic improvement of wheat. Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGAmAm), is central to wheat evolution, domestication and genetic improvement1. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu2, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome3) and Ae. tauschii (the donor of the D genome4), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.

Unit commitment for systems with significant wind penetration

Abstract: The stochastic nature of wind alters the unit commitment and dispatch problem. By accounting for this uncertainty when scheduling the system, more robust schedules are produced, which should, on average, reduce expected costs. In this paper, the effects of stochastic wind and load on the unit commitment and dispatch of power systems with high levels of wind power are examined. By comparing the costs, planned operation and performance of the schedules produced, it is shown that stochastic optimization results in less costly, of the order of 0.25%, and better performing schedules than deterministic optimization. The impact of planning the system more frequently to account for updated wind and load forecasts is then examined. More frequent planning means more up to date forecasts are used, which reduces the need for reserve and increases performance of the schedules. It is shown that mid merit and peaking units and the interconnection are the most affected parts of the system where uncertainty of wind is concerned

BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression

Abstract: We have identified a novel protein, BAP1, which binds to the RING finger domain of the Breast/Ovarian Cancer Susceptibility Gene product, BRCA1. BAP1 is a nuclear-localized, ubiquitin carboxy-terminal hydrolase, suggesting that deubiquitinating enzymes may play a role in BRCA1 function. BAP1 binds to the wild-type BRCA1-RING finger, but not to germline mutants of the BRCA1-RING finger found in breast cancer kindreds. BAP1 and BRCA1 are temporally and spatially co-expressed during murine breast development and remodeling, and show overlapping patterns of subnuclear distribution. BAP1 resides on human chromosome 3p21.3; intragenic homozygous rearrangements and deletions of BAP1 have been found in lung carcinoma cell lines. BAP1 enhances BRCA1-mediated inhibition of breast cancer cell growth and is the first nuclear-localized ubiquitin carboxy-terminal hydrolase to be identified. BAP1 may be a new tumor suppressor gene which functions in the BRCA1 growth control pathway.