Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36

Kufor-Rakeb syndrome is an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration. The onset is in the teenage years with clinical features of Parkinson’s disease plus spasticity, supranuclear upgaze paresis, and dementia. Brain scans show atrophy of the globus pallidus and pyramids and, later, widespread cerebral atrophy. We report linkage in Kufor- Rakeb syndrome to a 9 cM region of chromosome 1p36 delineated by the markers D1S436 and D1S2843, with a maximum multipoint lod score of 3.6. (J Med Genet 2001;38:680–682

Towards data grids for microarray expression profiles

The UK DTI funded Biomedical Research Informatics Delivered by Grid Enabled Services (BRIDGES) project developed a Grid infrastructure through which research into the genetic causes of hypertension could be supported by scientists within the large Wellcome Trust funded Cardiovascular Functional Genomics project. The BRIDGES project had a focus on developing a compute Grid and a data Grid infrastructure with security at its heart. Building on the work within BRIDGES, the BBSRC funded Grid enabled Microarray Expression Profile Search (GEMEPS) project plans to provide an enhanced data Grid infrastructure to support richer queries needed for the discovery and analysis of microarray data sets, also based upon a fine-grained security infrastructure. This paper outlines the experiences gained within BRIDGES and outlines the status of the GEMEPS project, the open challenges that remain and plans for the future

Bioethics: Reincarnation of Natural Philosophy in Modern Science

The theory of evolution of complex and comprising of human systems and algorithm for its constructing are the synthesis of evolutionary epistemology, philosophical anthropology and concrete scientific empirical basis in modern (transdisciplinary) science. «Trans-disciplinary» in the context is interpreted as a completely new epistemological situation, which is fraught with the initiation of a civilizational crisis. Philosophy and ideology of technogenic civilization is based on the possibility of unambiguous demarcation of public value and descriptive scientific discourses (1), and the object and subject of the cognitive process (2). Both of these attributes are no longer valid. For mass, everyday consciousness and institutional philosophical tradition it is intuitively obvious that having the ability to control the evolutionary process, Homo sapiens came close to the borders of their own biological and cultural identity. The spontaneous coevolutionary process of interaction between the «subject» (rational living organisms) and the «object» (material world), is the teleological trend of the movement towards the complete rationalization of the World as It Is, its merger with the World of Due. The stratification of the global evolutionary process into selective and semantic (teleological) coevolutionary and therefore ontologically inseparable components follows. With the entry of anthropogenic civilization into the stage of the information society, firsty, the post-academic phase of the historical evolution of scientific rationality began, the attributes of which are the specific methodology of scientific knowledge, scientific ethos and ontology. Bioethics as a phenomenon of intellectual culture represents a natural philosophical core of modern post- academic (human-dimensional) science, in which the ethical neutrality of scientific theory principle is inapplicable, and elements of public-axiological and scientific-descriptive discourses are integrated into a single logic construction. As result, hermeneutics precedes epistemology not only methodologically, but also meaningfully, and natural philosophy is regaining the status of the backbone of the theory of evolution – in an explicit for

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Five Year Cumulative Index: Articles and Comments by Title

A five year cumulative index of articles and comments by title for the journal RISK

Genetics Analysis Workshop 16 Problem 2: tTe Framingham Heart Study Data

Genetic Analysis Workshop 16 (GAW16) Problem 2 presented data from the Framingham Heart Study (FHS), an observational, prospective study of risk factors for cardiovascular disease begun in 1948. Data have been collected in three generations of family participants in the study and the data presented for GAW16 included phenotype data from all three generations, with four examinations of data collected repeatedly for the first two generations. The trait data consisted of information on blood pressure, hypertension treatment, lipid levels, diabetes and blood glucose, smoking, alcohol consumed, weight, and coronary heart disease incidence. Additionally, genotype data obtained through a genome-wide scan (FHS SHARe) of 550,000 single-nucleotide polymorphisms from Affymetrix chips were included with the GAW16 data. The genotype data were also used for GAW16 Problem 3, where simulated phenotypes were generated using the actual FHS genotypes. These data served to provide investigators with a rich resource to study the behavior of genome-wide scans with longitudinally collected family data and to develop and apply new procedures.National Heart, Lung and Blood Institute (2 N01-HC-25195-06); National Institutes of Health (National Institute of General Medical Sciences R01 GM031575

Reevaluating Assembly Evaluations with Feature Response Curves: GAGE and Assemblathons

In just the last decade, a multitude of bio-technologies and software pipelines have emerged to revolutionize genomics. To further their central goal, they aim to accelerate and improve the quality of de novo whole-genome assembly starting from short DNA reads. However, the performance of each of these tools is contingent on the length and quality of the sequencing data, the structure and complexity of the genome sequence, and the resolution and quality of long-range information. Furthermore, in the absence of any metric that captures the most fundamental "features" of a high-quality assembly, there is no obvious recipe for users to select the most desirable assembler/assembly. International competitions such as Assemblathons or GAGE tried to identify the best assembler(s) and their features. Some what circuitously, the only available approach to gauge de novo assemblies and assemblers relies solely on the availability of a high-quality fully assembled reference genome sequence. Still worse, reference-guided evaluations are often both difficult to analyze, leading to conclusions that are difficult to interpret. In this paper, we circumvent many of these issues by relying upon a tool, dubbed FRCbam, which is capable of evaluating de novo assemblies from the read-layouts even when no reference exists. We extend the FRCurve approach to cases where lay-out information may have been obscured, as is true in many deBruijn-graph-based algorithms. As a by-product, FRCurve now expands its applicability to a much wider class of assemblers -- thus, identifying higher-quality members of this group, their inter-relations as well as sensitivity to carefully selected features, with or without the support of a reference sequence or layout for the reads. The paper concludes by reevaluating several recently conducted assembly competitions and the datasets that have resulted from them.Comment: Submitted to PLoS One. Supplementary material available at http://www.nada.kth.se/~vezzi/publications/supplementary.pdf and http://cs.nyu.edu/mishra/PUBLICATIONS/12.supplementaryFRC.pd