Top 4 Biorxiv Papers Today in Genetics


1.997 Mikeys
#1. Shared regulatory pathways reveal novel genetic correlations between grip strength and neuromuscular disorders
Sreemol Gokuladhas, William Schierding, David Cameron-Smith, Melissa Wake, Emma Scotter, Justin M. O'Sullivan
Background: Muscle weakness and muscle wasting can be a consequence of aging (sarcopenia) and neuromuscular disorders (NMD). Genome-wide association (GWA) studies have identified genetic variants associated with grip strength (GS, an inverse measure of muscle weakness) and NMD (multiple sclerosis (MS), myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS)). However, how these variants contribute to the muscle weakness caused by aging or NMD remains obscure. Methods: We have integrated GS and NMD associated SNPs in a multimorbid analysis that leverages high-throughput chromatin interaction (Hi-C) data and expression quantitative trait loci (eQTL) data to identify allele-specific gene regulation (i.e. eGenes). Pathways and shared drug targets that are enriched by colocalised eGenes were then identified using pathway and drug enrichment analysis. Results: We identified gene regulatory mechanisms (eQTL-eGene effects) associated with GS, MG, MS, and ALS. The eQTLs associated with GS regulate a subset of eGenes that are also...
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biorxivpreprint: Shared regulatory pathways reveal novel genetic correlations between grip strength and neuromuscular disorders https://t.co/oeqFt4UMQp #bioRxiv
biorxiv_genetic: Shared regulatory pathways reveal novel genetic correlations between grip strength and neuromuscular disorders https://t.co/OYHLK8Sm56 #biorxiv_genetic
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1.997 Mikeys
#2. The tempo and mode of angiosperm mitochondrial genome divergence inferred from intraspecific variation in Arabidopsis thaliana
Zhiqiang Wu, Gus Waneka, Daniel B Sloan
The mechanisms of sequence divergence in angiosperm mitochondrial genomes have long been enigmatic. In particular, it is difficult to reconcile the rapid divergence of intergenic regions that can make non-coding sequences almost unrecognizable even among close relatives with the unusually high levels of sequence conservation found in genic regions. It has been hypothesized that different mutation/repair mechanisms act on genic and intergenic sequences or alternatively that mutational input is relatively constant but that selection has strikingly different effects on these respective regions. To test these alternative possibilities, we analyzed mtDNA divergence within Arabidopsis thaliana , including variants from the 1001 Genomes Project and changes accrued in published mutation accumulation (MA) lines. We found that base-substitution frequencies are relatively similar for intergenic regions and synonymous sites in coding regions, whereas indel and nonsynonymous substitutions rates are greatly depressed in coding regions,...
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biorxivpreprint: The tempo and mode of angiosperm mitochondrial genome divergence inferred from intraspecific variation in Arabidopsis thaliana https://t.co/18OyyVNHcV #bioRxiv
biorxiv_genetic: The tempo and mode of angiosperm mitochondrial genome divergence inferred from intraspecific variation in Arabidopsis thaliana https://t.co/zwWYLf1lJD #biorxiv_genetic
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1.997 Mikeys
#3. PQM-1 controls hypoxic survival via regulation of lipid metabolism
Thomas Heimbucher, Julian Hog, Coleen T. Murphy
Animals have evolved responses to low oxygen conditions to ensure their survival. Here we have identified the C. elegans zinc finger transcription factor PQM-1 as a regulator of the hypoxic stress response. PQM-1 is required for the longevity of insulin signaling mutants, but surprisingly, loss of PQM-1 increases survival under hypoxic conditions. PQM-1 functions as a metabolic regulator by controlling oxygen consumption rates, suppressing hypoxic glycogen levels, and inhibiting the expression of the sorbitol dehydrogenase-1 SODH-1, a crucial enzyme for sugar metabolism. PQM-1 promotes intestinal fat metabolism by activating the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity enhances fat accumulation in embryos under hypoxic conditions, thereby increasing survival rates of arrested progeny during hypoxia. Thus, while pqm-1 mutants increase survival of mothers, ultimately this loss is detrimental to progeny survival. Our data support a model in...
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biorxivpreprint: PQM-1 controls hypoxic survival via regulation of lipid metabolism https://t.co/SCYP9X0qbK #bioRxiv
biorxiv_genetic: PQM-1 controls hypoxic survival via regulation of lipid metabolism https://t.co/j1HGt7G3dH #biorxiv_genetic
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Total Words: 8413
Unqiue Words: 2608

1.997 Mikeys
#4. Evolutionary dynamics of the SKN-1 → MED → END-1,3 regulatory gene cascade in Caenorhabditis endoderm specification
Morris F Maduro
Gene regulatory networks (GRNs) with GATA factors are important in animal development, and evolution of such networks is an important problem in the field. In the nematode, Caenorhabditis elegans , the endoderm (gut) is generated from a single embryonic precursor, E. The gut is specified by an essential cascade of transcription factors in a GRN, with the maternal factor SKN-1 at the top, activating expression of the redundant med-1,2 divergent GATA factor genes, with the combination of all three contributing to activation of the paralogous end-3 and end-1 canonical GATA factor genes. In turn, these factors activate the GATA factors genes elt-2 and elt-7 to regulate intestinal fate. In this work, genome sequences from over two dozen species within the Caenorhabditis genus are used to identify putative orthologous genes encoding the MED and END-1,3 factors. The predictions are validated by comparison of gene structure, protein conservation, and putative cis -regulatory sites. The results show that all three factors occur together,...
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biorxivpreprint: Evolutionary dynamics of the SKN-1 -> MED -> END-1,3 regulatory gene cascade in Caenorhabditis endoderm specification https://t.co/x9IczHISAK #bioRxiv
biorxiv_genetic: Evolutionary dynamics of the SKN-1 -> MED -> END-1,3 regulatory gene cascade in Caenorhabditis endoderm specification https://t.co/BDuchkwUMm #biorxiv_genetic
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Authors: 1
Total Words: 0
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