Connection Between Epigenome, Selective Mutability, Evolution, and Human Disease
Li, Harris et al., PLoS Genetics
Researchers at the Baylor College of Medicine and elsewhere propose a "connection between the epigenome, selective mutability, evolution, and human disease" based on the findings of their study on associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination mediated by low-copy repeats. "Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability," the Baylor-led team writes.
This Week in Science
A team led by investigators at the Max-Delbrück-Center for Molecular Medicine shows in a Science paper published online in advance this week that the transcription factor c-Maf/c-MAF "is crucial for mechanosensory function in mice and humans." The team also reports that humans with a dominant mutation in the c-MAF gene are sensitive to high-frequency vibrations. "Our work identifies a key transcription factor specifying development and function of mechanoreceptors and their end organs," the authors write.
Investigators at the National Institute of Allergy and Infectious Diseases show that "Lin28b reprograms adult bone marrow hematopoietic progenitors to mediate fetal-like lymphopoiesis" in a Science paper published online in advance. More specifically, the team demonstrates that ectopic expression of Lin28 endows hematopoietic stem-progenitor cells with "the ability to mediate multilineage reconstitution that resembles fetal lymphopoiesis, including increased development of B-1a, marginal zone B, gamma/delta T cells, and natural killer T cells."
Over in this week's issue, a team led by the Wellcome Trust Sanger Institute's Daniel MacArthur estimate that human genomes contain around 100 "genuine LoF [loss-of-function] variants, with [approximately] 20 genes completely inactivated." Further, the Sanger-led team identifies "rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes." Our sister publication GenomeWeb Daily News has more on this study.
Finally in Science Translational Medicine, a public-private team led by investigators at Regulus Therapeutics in San Diego shows in two mouse models that "miR-21 contributes to fibrogenesis and epithelial injury in the kidney ... and is a candidate target for antifibrotic therapies."