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Science ; 374(6569): eabj1541, 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1526448


Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 connections that highlights strong cross-disease biological convergence. This proteo-genomic map provides a framework to connect etiologically related diseases, to provide biological context for new or emerging disorders, and to integrate different biological domains to establish mechanisms for known gene-disease links. Our results identify proteo-genomic connections within and between diseases and establish the value of cis-protein variants for annotation of likely causal disease genes at loci identified in genome-wide association studies, thereby addressing a major barrier to experimental validation and clinical translation of genetic discoveries.

Blood Proteins/genetics , Disease/genetics , Genome, Human , Genomics , Proteins/genetics , Proteome , Aging , Alternative Splicing , Blood Proteins/metabolism , COVID-19/genetics , Connective Tissue Diseases/genetics , Disease/etiology , Drug Development , Female , Gallstones/genetics , Genetic Association Studies , Genetic Variation , Genome-Wide Association Study , Humans , Internet , Male , Phenotype , Proteins/metabolism , Quantitative Trait Loci , Sex Characteristics
Cells ; 10(9)2021 09 13.
Article in English | MEDLINE | ID: covidwho-1468387


Neutrophils are key cells of the innate immune system. It is now understood that this leukocyte population is diverse in both the basal composition and functional plasticity. Underlying this plasticity is a post-translational framework for rapidly achieving early activation states, but also a transcriptional capacity that is becoming increasingly recognized by immunologists. Growing interest in the contribution of neutrophils to health and disease has resulted in more efforts to describe their transcriptional activity. Whilst initial efforts focused predominantly on understanding the existing biology, investigations with advanced methods such as single cell RNA sequencing to understand interactions of the entire immune system are revealing higher flexibility in neutrophil transcription than previously thought possible and multiple transition states. It is now apparent that neutrophils utilise many forms of RNA in the regulation of their function. This review collates current knowledge on the nuclei structure and gene expression activity of human neutrophils across homeostasis and disease, before highlighting knowledge gaps that are research priority areas.

Disease/etiology , Gene Expression Regulation , Immunity, Innate/immunology , Neutrophils/immunology , Neutrophils/pathology , Transcriptome , Animals , Homeostasis , Humans , Neutrophils/metabolism , Signal Transduction
Adv Genet ; 106: 1-4, 2020.
Article in English | MEDLINE | ID: covidwho-634816


This current volume is, in many ways, a 2020 update to the important 1999-2000 compendium by Sir Fred Hoyle and Professor N. Chandra Wickramasinghe's "Astronomical Origins of life: Steps towards Panspermia." The emerging new paradigm of biology that connects life on Earth with the wider cosmos is covered in considerable depth showing that terrestrial biological evolution is best understood as a cosmically derived habitat and an interconnected genetic system. The various chapters here discuss all aspects of this interconnectedness, particularly relevant now in this time of the coronavirus pandemic (COVID-19) as the human race reacts to the many microbes and viral pathogens that arrive regularly from space.

Biological Evolution , Environment , Exobiology , Host-Pathogen Interactions/physiology , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Disease/etiology , Ecosystem , Extraterrestrial Environment , Humans , Models, Biological , Origin of Life , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2