Search results for "GENOMES"
showing 10 items of 56 documents
Comparison of CRISPR and Marker-Based Methods for the Engineering of Phage T7
2020
This article belongs to the Section Bacterial Viruses.
2018
In many viral infections, a large number of different genetic variants can coexist within a host, leading to more virulent infections that are better able to evolve antiviral resistance and adapt to new hosts. But how is this diversity maintained? Why do faster-growing variants not outcompete slower-growing variants, and erode this diversity? One hypothesis is if there are mutually beneficial interactions between variants, with host cells infected by multiple different viral genomes producing more, or more effective, virions. We modelled this hypothesis with both mathematical models and simulations, and found that moderate levels of beneficial coinfection can maintain high levels of coexist…
Exploiting Helminth–Host Interactomes through Big Data
2017
Helminths facilitate their parasitic existence through the production and secretion of different molecules, including proteins. Some helminth proteins can manipulate the host's immune system, a phenomenon that is now being exploited with a view to developing therapeutics for inflammatory diseases. In recent years, hundreds of helminth genomes have been sequenced, but as a community we are still taking baby steps when it comes to identifying proteins that govern host-helminth interactions. The information generated from genomic, immunomic, and proteomic studies, as well as from cutting-edge approaches such as proteogenomics, is leading to a substantial volume of big data that can be utilised…
Haplotype reference consortium panel: Practical implications of imputations with large reference panels.
2017
Contains fulltext : 177754.pdf (Publisher’s version ) (Open Access) Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts usin…
Missense Mutations of Human Hsp60: A Computational Analysis to Unveil Their Pathological Significance
2020
Two chaperonopathies have been linked to mutations in the human hsp60 (hHsp60; HSPD1) gene, but other existing variants might cause diseases, even if there is no comprehensive information about this possibility. To fill this vacuum, which might be at the basis of misdiagnoses or simply ignorance of chaperonopathies in patients who would benefit by proper identification of their ailments, we searched the sequenced human genomes available in public databases to determine the range of missense mutations in the single hsp60 gene. A total of 224 missense mutations were identified, including those already characterized. Detailed examination of these mutations was carried out to assess their possi…
Ancient bacterial genomes reveal a high diversity of Treponema pallidum Strains in early Modern Europe
2020
Syphilis is a globally re-emerging disease, which has marked European history with a devastating epidemic at the end of the 15th century. Together with non-venereal treponemal diseases, like bejel and yaws, which are found today in subtropical and tropical regions, it currently poses a substantial health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis’ potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a high diversity of Treponema pallidum in early modern Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and y…
Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.
2016
Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing t…
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
2018
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…
Collective Infectious Units in Viruses
2017
Increasing evidence indicates that viruses do not simply propagate as independent virions among cells, organs, and hosts. Instead, viral spread is often mediated by structures that simultaneously transport groups of viral genomes, such as polyploid virions, aggregates of virions, virion-containing proteinaceous structures, secreted lipid vesicles, and virus-induced cell-cell contacts. These structures increase the multiplicity of infection, independently of viral population density and transmission bottlenecks. Collective infectious units may contribute to the maintenance of viral genetic diversity, and could have implications for the evolution of social-like virus-virus interactions. These…
Detailed analysis of inversions predicted between two human genomes: errors, real polymorphisms, and their origin and population distribution.
2016
The growing catalogue of structural variants in humans often overlooks inversions as one of the most difficult types of variation to study, even though they affect phenotypic traits in diverse organisms. Here, we have analysed in detail 90 inversions predicted from the comparison of two independently assembled human genomes: the reference genome (NCBI36/HG18) and HuRef. Surprisingly, we found that two thirds of these predictions (62) represent errors either in assembly comparison or in one of the assemblies, including 27 misassembled regions in HG18. Next, we validated 22 of the remaining 28 potential polymorphic inversions using different PCR techniques and characterized their breakpoints …