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Genome Biology Papers Look at Neuronal Epigenetics in Parkinson's, Differential Expression Method, More

Researchers from the Van Andel Institute and Michigan State University document DNA methylation differences in neurons from each hemisphere in the prefrontal cortex of dozens of individuals with or without Parkinson's disease — hemispheric asymmetry that appears to contribute to symptom lateralization in individuals with Parkinson's disease. From a series of array-based DNA methylation profiling, bisulfite sequencing-based fine-mapping, regulatory element, and RNA sequence-based expression analyses, the team saw an overall decline in hemispheric asymmetry in the neuronal epigenomes of aging individuals. In contrast, hemispheric asymmetry appeared more pronounced in individuals with Parkinson's disease, particularly when it came to regulatory marks affecting neurodevelopment, immune, and synapse-related genes.

A Chinese Academy of Sciences-led team outlines a molecular barcoding-based RNA sequencing approach for taking a look at differential gene expression. The method — known as "differential expression analysis by barcoded sequencing," or Decode-seq — makes it possible to significantly bump up the biological replicates available for such analyses, the authors say, arguing that "[u]nless samples are precious, full-length sequencing is necessary, or underpower is not an issue, there are few reasons to use inadequate replicates." When the team applied Decode-seq to dozens of male or female medaka, Oryzias latipes, for example, it tracked down hundreds of genes with differential gene expression depending on sex in the freshwater fish, including genes contributing to germ cell development.

Researchers in Australia, the UK, and the US present findings from a study of osteoporosis, focusing on regulatory functions for genetic risk variants previously implicated in estimated bone mineral density with genome-wide association studies in humans. Starting with more than 1,100 variants at 518 loci from a published UK Biobank-based GWAS, the team looked for overlap between risk variants and expression quantitative trait loci (eQTLs) that are active in bone resorption-related human osteoclast cells. The search led to 21 loci containing both GWAS and cis-eQTL signals, the authors report, highlighting 53 related genes. Their subsequent mouse knockout experiments suggested at least one of these genes, RIPK3, may contribute to bone microarchitecture and osteoclast number.