We have conducted a multistage genomewide association study, using 1,620,742 single-nucleotide polymorphisms to systematically investigate the genetic factors influencing intrinsic skin pigmentation ...in a population of South Asian descent. Polymorphisms in three genes—
SLC24A5, TYR, and
SLC45A2—yielded highly significant replicated associations with skin-reflectance measurements, an indirect measure of melanin content in the skin. The associations detected in these three genes, in an additive manner, collectively account for a large fraction of the natural variation of skin pigmentation in a South Asian population. Our study is the first to interrogate polymorphisms across the genome, to find genetic determinants of the natural variation of skin pigmentation within a human population.
We analyzed the whole-genome sequences of a family of four, consisting of two siblings and their parents. Family-based sequencing allowed us to delineate recombination sites precisely, identify 70% ...of the sequencing errors (resulting in > 99.999% accuracy), and identify very rare single-nucleotide polymorphisms. We also directly estimated a human intergeneration mutation rate of approximately 1.1 x 10⁻⁸ per position per haploid genome. Both offspring in this family have two recessive disorders: Miller syndrome, for which the gene was concurrently identified, and primary ciliary dyskinesia, for which causative genes have been previously identified. Family-based genome analysis enabled us to narrow the candidate genes for both of these Mendelian disorders to only four. Our results demonstrate the value of complete genome sequencing in families.
Dual‐function electrocatalytic and macroporous hollow‐fiber cathodes are recently proposed as promising advanced material for maximizing the conversion of waste streams such as wastewater and waste ...CO2 to valuable resources (e.g., clean freshwater, energy, value‐added chemicals) in microbial electrochemical systems. The first part of this progress report reviews recent developments in this type of cathode architecture for the simultaneous recovery of clean freshwater and energy from wastewater. Critical insights are provided on suitable materials for fabricating these cathodes, as well as addressing some challenges in the fabrication process with proposed strategies to overcome them. The second and complementary part of the progress report highlights how the unique features of this cathode architecture can solve one of the intrinsic bottlenecks (gas–liquid mass transfer limitation) in the application of microbial electrochemical systems for CO2 reduction to value‐added products. Strategies to further improve the availability of CO2 to microbial catalysts on the cathode are proposed. The importance of understanding microbe–cathode interactions, as well as electron transfer mechanisms at the cathode–cell and cell–cell interface to better design dual‐function macroporous hollow‐fiber cathodes, is critically discussed with insights on how the choice of material is important in facilitating direct electron transfer versus mediated electron transfer.
Electrocatalytic and macroporous hollow‐fiber cathodes for converting waste streams (e.g., wastewater and CO2) to valuable resources (clean water, energy, and value‐added products) are reviewed.
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small-cell lung carcinomas in smokers being the predominant form of the disease. Although previous studies have ...identified important common somatic mutations in lung cancers, they have primarily focused on a limited set of genes and have thus provided a constrained view of the mutational spectrum. Recent cancer sequencing efforts have used next-generation sequencing technologies to provide a genome-wide view of mutations in leukaemia, breast cancer and cancer cell lines. Here we present the complete sequences of a primary lung tumour (60x coverage) and adjacent normal tissue (46x). Comparing the two genomes, we identify a wide variety of somatic variations, including >50,000 high-confidence single nucleotide variants. We validated 530 somatic single nucleotide variants in this tumour, including one in the KRAS proto-oncogene and 391 others in coding regions, as well as 43 large-scale structural variations. These constitute a large set of new somatic mutations and yield an estimated 17.7 per megabase genome-wide somatic mutation rate. Notably, we observe a distinct pattern of selection against mutations within expressed genes compared to non-expressed genes and in promoter regions up to 5 kilobases upstream of all protein-coding genes. Furthermore, we observe a higher rate of amino acid-changing mutations in kinase genes. We present a comprehensive view of somatic alterations in a single lung tumour, and provide the first evidence, to our knowledge, of distinct selective pressures present within the tumour environment.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present study aims to develop an ecofriendly, chelant-assisted extraction methodology for significant recovery of heavy metals (cobalt (Co), molybdenum (Mo)) from hydroprocessing spent catalyst. ...Ethylene diamine tetraacetic acid (EDTA) was employed for metal mobilization in the extraction process. The possibility of internal and external mass transfer resistance was investigated to improve the diffusion rate of reactants, while kinetic aspects were studied to achieve thermodynamic equilibrium for the process. Percentage distribution of various protonation stages of EDTA was explored to understand the conjugate base and ligand precursor and to improve the effect of reaction pH on extraction efficiency. Extraction of 80.4% Co and 84.9% Mo was achieved at optimum reaction conditions. Selective precipitation of metals was attained according to maximum solubility of metal oxides at different pH regions. Efforts were also made to recycle the recovered EDTA, recovered support material, and extracted metals. Significant metal extraction efficiency (72.7% Co and 76.5% Mo) was observed with recovered EDTA even after the fourth cycle of operation which may provide economic consistency to the extraction process. The extracted metals were impregnated on recovered alumina to synthesize fresh catalyst. Structural analysis of spent catalyst, recovered support material, and synthesized catalyst from extracted metals suggested successful recovery and recycling of metals. This work offers an incentive to the industrial practice for waste minimization, recycling of the extracted metals, and the noncorrosive, ecofriendly approach for metal extraction from spent catalyst.
Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported, but its scale, impact and contribution to HCC ...development is not clear. Here, we sequenced the tumor and nontumor genomes (>80× coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240× coverage revealed a proportionally higher number of integration sites. Clonal expansion of HBV-integrated hepatocytes was found specifically in tumor samples. We observe a diverse collection of genomic perturbations near viral integration sites, including direct gene disruption, viral promoter-driven human transcription, viral-human transcript fusion, and DNA copy number alteration. Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals.
Recent advances in whole-genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to ...describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, long fragment read (LFR) technology, which is similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ∼100 picograms of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants were assembled into long haplotype contigs. Removal of false positive single nucleotide variants not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 megabases. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 ...colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
Literature suggests that ethylene-diamine-tetraacetic acid (EDTA) has been proved as a successful chelating agent for the extraction of metals from soils and spent catalysts. EDTA, however, is quite ...persistent in the environment due to its low biodegradability, thus its use becomes a matter of environmental concern. Therefore, to minimize the potential environmental risks, a new chelating agent S,S-ethylene-diamine-disuccinic-acid (S,S-EDDS) can be considered as an environmentally benign substitute for EDTA due to its easy biodegradation capability. The present study focuses on the effectiveness of biodegradable chelating agent S,S-EDDS for extraction of nickel from the spent catalyst of fertilizer industry. Experiments were carried out in batch mode under reflux conditions and process design parameters were optimized to maximize the extraction efficiency. Ni extraction of 84% was attained at optimum reaction condition in one cycle run. Dechelation of Ni-EDDS complex was performed at pH 5 where more than 96% EDDS was recovered. Results of the present study were compared with the previously studied chelating agent EDTA at optimum reaction conditions reported in literature. It was observed that S,S-EDDS requires a narrower pH range as compared to EDTA for chelation–dechelation process. Thus milder reaction conditions were employed for metal extraction using EDDS which is favorable to select the material of construction of equipment, in addition to the added advantage of biodegradability. Kinetic study was also performed for the noncatalyzed extraction process using shrinking core model and the process was found to be diffusion controlled under experimental conditions.
In a genomewide association study of North Americans of European descent, followed by a Swedish replication analysis, investigators showed that in addition to the previously described loci at ...HLA-DRB1,
IRF5,
and
STAT4,
two new loci confer susceptibility to systemic lupus erythematosus. These loci are close to genes that encode B lymphoid tyrosine kinase and integrin alpha M.
A genomewide association study showed that two new loci confer susceptibility to systemic lupus erythematosus. These loci are close to genes that encode B lymphoid tyrosine kinase and integrin alpha M.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with strong genetic and environmental components.
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Autoantibodies play an important role in the pathogenesis of SLE, and the diverse clinical manifestations of the disease are caused by the deposition of antibody-containing immune complexes in blood vessels, leading to inflammation in the kidney, brain, and skin. Direct pathogenic effects of the autoantibodies contribute to hemolytic anemia and thrombocytopenia.
During the past 20 years, many linkage and candidate-gene studies have been performed to identify genetic factors contributing to a susceptibility to SLE. For example, haplotypes carrying the HLA class II alleles DRB1*0301 . . .
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