Uppsala University

About: Uppsala University is a education organization based out in Uppsala, Sweden. It is known for research contribution in the topics: Population & Insulin. The organization has 36485 authors who have published 107509 publications receiving 4220668 citations. The organization is also known as: Uppsala universitet & uu.se.

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

Abstract: 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 ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% 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/β-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.

Radical prostatectomy versus watchful waiting in early prostate cancer.

Abstract: BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now repo ...

A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma.

Abstract: Sunlight is a carcinogen to which everyone is exposed. Its UV component is the major epidemiologic risk factor for squamous cell carcinoma of the skin. Of the multiple steps in tumor progression, those that are sunlight-related would be revealed if they contained mutations specific to UV. In a series of New England and Swedish patients, we find that 14/24 (58%) of invasive squamous cell carcinomas of the skin contain mutations in the p53 tumor suppressor gene, each altering the amino acid sequence. Involvement of UV light in these p53 mutations is indicated by the presence in three of the tumors of a CC----TT double-base change, which is only known to be induced by UV. UV is also implicated by a UV-like occurrence of mutations exclusively at dipyrimidine sites, including a high frequency of C----T substitutions. p53 mutations in internal malignancies do not show these UV-specific mutations. The dipyrimidine specificity also implicates dipyrimidine photoproducts containing cytosine as oncogenic photoproducts. We believe these results identify a carcinogen-related step in a gene involved in the subsequent human cancer.

NeighborNet: An Agglomerative Method for the Construction of Planar Phylogenetic Networks

Abstract: We introduce NeighborNet, a network construction and data representation method that combines aspects of the neighbor joining (NJ) and SplitsTree. Like NJ, NeighborNet uses agglomeration: taxa are combined into progressively larger and larger overlapping clusters. Like SPLITSTREE, NeighborNet constructs networks rather than trees, and so can be used to represent multiple phylogenetic hypotheses simultaneously, or to detect complex evolutionary processes like recombination, lateral transfer and hybridization. NeighborNet tends to produce networks that are substantially more resolved than those made with SPLITSTREE. The method is efficient (O(n3) time) and is well suited for the preliminary analyses of complex phylogenetic data. We report results of three case studies: one based on mitochondrial gene order data from early branching eukaryotes, another based on nuclear sequence data from New Zealand alpine buttercups (Ranunculi), and a third on poorly corrected synthetic data.