Genetic predisposition has been shown to contribute substantially to the age at which we die. Genome-wide association studies (GWASs) have linked more than 20 loci to phenotypes related to human lifespan. However, little is known about how lifespan is impacted by gene loss of function.
View Article and Find Full Text PDFComput Struct Biotechnol J
March 2022
With advances in NGS technologies, transcriptional profiling of human tissue across many diseases is becoming more routine, leading to the generation of petabytes of data deposited in public repositories. There is a need for bench scientists with little computational expertise to be able to access and mine this data to understand disease pathology, identify robust biomarkers of disease and the effect of interventions ( or ). To this end we release an open source analytics and visualization platform for expression data called OmicsView, http://omicsview.
View Article and Find Full Text PDFCellDepot containing over 270 datasets from 8 species and many tissues serves as an integrated web application to empower scientists in exploring single-cell RNA-seq (scRNA-seq) datasets and comparing the datasets among various studies through a user-friendly interface with advanced visualization and analytical capabilities. To begin with, it provides an efficient data management system that users can upload single cell datasets and query the database by multiple attributes such as species and cell types. In addition, the graphical multi-logic, multi-condition query builder and convenient filtering tool backed by MySQL database system, allows users to quickly find the datasets of interest and compare the expression of gene(s) across these.
View Article and Find Full Text PDFThe hydrological cycle intensifies under global warming with precipitation increases. How the increased precipitation varies temporally at a given location has vital implications for regional climates and ecosystem services. On the basis of ensemble climate model projections under a high-emission scenario, here, we show that approximately two-thirds of land on Earth will face a "wetter and more variable" hydroclimate on daily to multiyear time scales.
View Article and Find Full Text PDFis an emerging multidrug-resistant fungal pathogen. Since first reported in 2009, has caused healthcare outbreaks around the world, often involving high mortality. Identification of has been a major challenge as many common conventional laboratory methods cannot accurately detect it.
View Article and Find Full Text PDFFor many species, there is evidence that breeding performance changes as an individual ages. In iteroparous species, breeding performance often increases through early life and is expected to level out or even decline (senesce) later in life. An individual's sex and conditions experienced in early life may also affect breeding performance and how this changes with age.
View Article and Find Full Text PDFThe presence of ribonucleotides in genomic DNA is undesirable given their increased susceptibility to hydrolysis. Ribonuclease (RNase) H enzymes that recognize and process such embedded ribonucleotides are present in all domains of life. However, in unicellular organisms such as budding yeast, they are not required for viability or even efficient cellular proliferation, while in humans, RNase H2 hypomorphic mutations cause the neuroinflammatory disorder Aicardi-Goutières syndrome.
View Article and Find Full Text PDFThere is much interest in the mechanisms that regulate adult tissue homeostasis and their relationship to processes governing foetal development. Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature. Wt1 is vital for maintaining the mesenchymal-epithelial balance in these tissues and is required for the epithelial-to-mesenchyme transition (EMT) that generates coronary vascular progenitors.
View Article and Find Full Text PDFOphthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families.
View Article and Find Full Text PDFBackground: Parental consanguinity is a risk factor for congenital heart disease (CHD) worldwide, suggesting that a recessive inheritance model may contribute substantially to CHD. In Bangalore, India, uncle-niece and first cousin marriages are common, presenting the opportunity for an international study involving consanguinity mapping of structural CHD. We sought to explore the recessive model of CHD by conducting a genome-wide linkage analysis utilizing high-density oligonucleotide microarrays and enrolling 83 CHD probands born to unaffected consanguineous parents.
View Article and Find Full Text PDFThe methods to detect gene-gene interactions between variants in genome-wide association study (GWAS) datasets have not been well developed thus far. PLATO, the Platform for the Analysis, Translation and Organization of large-scale data, is a filter-based method bringing together many analytical methods simultaneously in an effort to solve this problem. PLATO filters a large, genomic dataset down to a subset of genetic variants, which may be useful for interaction analysis.
View Article and Find Full Text PDFIn a recent genome-wide association study (GWAS) based on 12,374 non-synonymous single nucleotide polymorphisms we identified a number of candidate multiple sclerosis susceptibility genes. Here, we describe the extended analysis of 17 of these loci undertaken using an additional 4234 patients, 2983 controls and 2053 trio families. In the final analysis combining all available data, we found that evidence for association was substantially increased for one of the 17 loci, rs34536443 from the tyrosine kinase 2 (TYK2) gene (P=2.
View Article and Find Full Text PDFIn addition to influencing climatic conditions directly through radiative forcing, increasing carbon dioxide concentration influences the climate system through its effects on plant physiology. Plant stomata generally open less widely under increased carbon dioxide concentration, which reduces transpiration and thus leaves more water at the land surface. This driver of change in the climate system, which we term 'physiological forcing', has been detected in observational records of increasing average continental runoff over the twentieth century.
View Article and Find Full Text PDFWe consider inference based on ensembles of climate model evaluations, and contrast the Monte Carlo approach, in which the evaluations are selected at random from the model-input space, with a more overtly statistical approach using emulators and experimental design.
View Article and Find Full Text PDFThe extent of genetic variation found in drug metabolism genes and its contribution to interindividual variation in response to medication remains incompletely understood. To better determine the identity and frequency of variation in 11 phase I drug metabolism genes, the exons and flanking intronic regions of the cytochrome P450 (CYP) isoenzyme genes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5 were amplified from genomic DNA and sequenced. A total of 60 kb of bi-directional sequence was generated from each of 93 human DNAs, which included Caucasian, African-American and Asian samples.
View Article and Find Full Text PDFComprehensive global climate models are the only tools that account for the complex set of processes which will determine future climate change at both a global and regional level. Planners are typically faced with a wide range of predicted changes from different models of unknown relative quality, owing to large but unquantified uncertainties in the modelling process. Here we report a systematic attempt to determine the range of climate changes consistent with these uncertainties, based on a 53-member ensemble of model versions constructed by varying model parameters.
View Article and Find Full Text PDFAlthough the predisposition to morbid obesity is heritable, the identities of the disease-causing genes are largely unknown. Therefore, we have conducted a genomewide search with 628 markers, using multigenerational Utah pedigrees to identify genes involved in predisposition to obesity. In the genomewide search, we identified a highly significant linkage to high body-mass index in female patients, at D4S2632, with a multipoint heterogeneity LOD (HLOD) score of 6.
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