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PNAS Papers on Asthma Methylation, Pleistocene Polar Bear, Rhabdomyosarcoma Gene Fusion

A team from the University of Chicago, the University of Washington, and other centers shares findings from a DNA methylation-based analysis of asthma, done to explore epigenetic explanations for the asthma risk in children born to mothers with the chronic condition. When they compared primary bronchial epithelial cell (BEC) methylation in samples from 32 asthma cases with affected mothers, 56 asthma cases without maternal asthma, and 42 unaffected controls, the researchers highlighted more than 550 differentially methylated sites in the maternal asthma individuals — findings they explored further with machine learning, related gene expression analyses, and other approaches. "These maternal asthma-associated methylation signatures were correlated with distinct gene regulatory pathways and clinical features," they note, suggesting "the prenatal environment in pregnancies of mothers with asthma alters epigenetically mediated developmental programs."

Investigators from the US, Singapore, Mexico, and other international centers present findings from a genome sequencing analysis of a 115,000- to 130,000-year-old polar bear (Ursus maritimus) sample found in Norway's Svalbard Archipelago, which offer clues to Ursus evolution. After using a combination of sequencing strategies to generate an ancient polar bear genome with 10-fold average coverage, the team analyzed the bear's nuclear genome and mitochondrial sequence alongside new genome sequences for 10 present-day polar or brown bears (U. arctos), uncovering ancient introgression from brown bears into polar bears. "Interspecific hybridization is a widespread phenomenon, but measuring its extent, directionality, and adaptive importance remains challenging," the team writes. "We find that the principal direction of ancient allele sharing was from brown bear into polar bear, although gene flow between them has likely been bidirectional."

A University of Virginia-led team digs into a rhabdomyosarcoma gene fusion that appears to activate the actin regulatory gene AVIL in the pediatric soft-tissue cancer. Past research suggests that the rhabdomyosarcoma-related MARS-AVIL fusion stems from a chromosomal inversion, the investigators explain. From their new gene expression, cell line, and mouse experiments, they found that dialing down activity of AVIL or the MARS-AVIL fusion decreases the growth of rhabdomyosarcoma cell cultures or xenografts in mice, the authors report, while boosting AVIL activity seemed to encourage the growth and movement of the rhabdomyosarcoma cells. "Tumors with AVIL dysregulation exhibit evidence of oncogene addiction," they suggest, noting that "AVIL is overexpressed in other sarcoma cells as well, and its expression correlates with clinical outcomes, with higher levels of AVIL expression being associated with worse prognosis."