scholarly journals Mapping the human genetic architecture of COVID-19: an update

2021 ◽  
Author(s):  
◽  
Andrea Ganna
Keyword(s):  
Public Health ◽  
Genetic Architecture ◽  
Disease Susceptibility ◽  
Meta Analysis ◽  
Host Genetics ◽  
Health Threat ◽  
Vaccination Rates ◽  
Genome Wide ◽  
Public Health Threat

The Coronavirus Disease 2019 (COVID-19) pandemic continues to pose a major public health threat especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity we formed the COVID19 Host Genetics Initiative. Here we present GWAS meta-analysis of up to 125,584 cases and over 2.5 million controls across 60 studies from 25 countries, adding 10 new genome-wide significant loci to the 13 we previously identified1. Genes in novel loci include SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.

scholarly journals High resolution genome-wide occupancy in Candida spp. using ChEC-seq

2020 ◽  
Author(s):  
Faiza Tebbji ◽  
Inès Khemiri ◽  
Adnane Sellam
Keyword(s):  
Public Health ◽  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
High Resolution ◽  
Transcriptional Regulator ◽  
Candida Spp ◽  
Health Threat ◽  
Genome Wide ◽  
Public Health Threat

AbstractTo persist in their hostile and dynamic human host environments, fungal pathogens has to sense and adapt by modulating their gene expression to fulfil their cellular needs. Understanding transcriptional regulation on a global scale would uncover cellular processes linked to persistence and virulence mechanisms that could be targeted for antifungal therapeutics. Infections associated with the yeast Candida albicans, a highly prevalent fungal pathogen, and the multi-resistant related species C. auris are becoming a serious public health threat. To define the set of a gene regulated by a transcriptional regulator in C. albicans, Chromatin Immuno-Precipitation (ChIP) based techniques including ChIP-chip or ChIP-seq has been widely used. Here, we describe a new set of PCR-based MNase-tagging plasmids for C. albicans and other Candida spp. to determine genome-wide location of any transcriptional regulator of interest using Chromatin endogenous cleavage (ChEC) coupled to high-throughput sequencing (ChEC-seq). The ChEC procedure does not require protein-DNA crosslinking or sonication avoiding thus artefacts related to epitope masking or the hyper-ChIPable euchromatic phenomenon. In a proof-of-concept application of ChEC-seq, we provided a high-resolution binding map of the SWI/SNF chromatin remodeling complex, a master regulator of fungal fitness in C. albicans in addition to the transcription factor NsiI that is an ortholog of the DNA-binding protein Reb1 for which genome-wide occupancy were previously established in Saccharomyces cerevisiae. The ChEC-seq procedure described here will allow a high-resolution genomic location definition which will enable a better understanding of transcriptional regulatory circuits that govern fungal fitness and drug resistance in these medically important fungi.ImportanceSystemic fungal infections caused by Candida albicans and the ‘superbug’ C. auris are becoming a serious public health threat. The ability of these yeasts to cause disease is linked to their faculty to modulate the expression of genes that mediate their escape from the immune surveillance and their persistence in the different unfavourable niches within the host. Comprehensive knowledge on gene expression control of fungal fitness is consequently an interesting framework for the identification of essential infection processes that could be hindered by chemicals as potential therapeutics. Here, we expanded the use of ChEC-seq, a technique that was initially developed in the yeast model Saccharomyces cerevisiae to identify genes that are modulated by a transcriptional regulator, to the pathogenic yeasts C. albicans and C. auris. This robust technique will allow a better characterization of key gene expression regulators and their contribution to virulence and antifungal resistance in these pathogenic yeasts.

scholarly journals A meta-analysis of genome-wide association studies for average daily gain and lean meat percentage in two Duroc pig populations

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shenping Zhou ◽  
Rongrong Ding ◽  
Fanming Meng ◽  
Xingwang Wang ◽  
Zhanwei Zhuang ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Growth And Development ◽  
Genetic Architecture ◽  
Association Studies ◽  
Meta Analysis ◽  
Average Daily Gain ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Daily Gain

Abstract Background Average daily gain (ADG) and lean meat percentage (LMP) are the main production performance indicators of pigs. Nevertheless, the genetic architecture of ADG and LMP is still elusive. Here, we conducted genome-wide association studies (GWAS) and meta-analysis for ADG and LMP in 3770 American and 2090 Canadian Duroc pigs. Results In the American Duroc pigs, one novel pleiotropic quantitative trait locus (QTL) on Sus scrofa chromosome 1 (SSC1) was identified to be associated with ADG and LMP, which spans 2.53 Mb (from 159.66 to 162.19 Mb). In the Canadian Duroc pigs, two novel QTLs on SSC1 were detected for LMP, which were situated in 3.86 Mb (from 157.99 to 161.85 Mb) and 555 kb (from 37.63 to 38.19 Mb) regions. The meta-analysis identified ten and 20 additional SNPs for ADG and LMP, respectively. Finally, four genes (PHLPP1, STC1, DYRK1B, and PIK3C2A) were detected to be associated with ADG and/or LMP. Further bioinformatics analysis showed that the candidate genes for ADG are mainly involved in bone growth and development, whereas the candidate genes for LMP mainly participated in adipose tissue and muscle tissue growth and development. Conclusions We performed GWAS and meta-analysis for ADG and LMP based on a large sample size consisting of two Duroc pig populations. One pleiotropic QTL that shared a 2.19 Mb haplotype block from 159.66 to 161.85 Mb on SSC1 was found to affect ADG and LMP in the two Duroc pig populations. Furthermore, the combination of single-population and meta-analysis of GWAS improved the efficiency of detecting additional SNPs for the analyzed traits. Our results provide new insights into the genetic architecture of ADG and LMP traits in pigs. Moreover, some significant SNPs associated with ADG and/or LMP in this study may be useful for marker-assisted selection in pig breeding.

scholarly journals 2-Mercaptomethyl-thiazolidines use conserved aromatic-S interactions to achieve broad-range inhibition of metallo-β-lactamases

2021 ◽  
Author(s):  
Maria-Agustina Rossi ◽  
Veronica Martinez ◽  
Philip Hinchliffe ◽  
Maria-Fernanda Mojica ◽  
Valerie Castillo ◽  
...  
Keyword(s):  
Public Health ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Health Threat ◽  
Public Health Threat

Infections caused by multidrug resistant (MDR) bacteria are a major public health threat. Carbapenems are among the most potent antimicrobial agents that are commercially available to treat MDR bacteria. Bacterial...

scholarly journals Unpasteurized Milk: A Continued Public Health Threat

2009 ◽  
Vol 48 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Jeffrey T. LeJeune ◽  
Päivi J. Rajala‐Schultz
Keyword(s):  
Public Health ◽  
Health Threat ◽  
Unpasteurized Milk ◽  
Public Health Threat
Sign in / Sign up

Export Citation Format

Share Document