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Genome Research Reports on Breast Cancer Insights from Dog Tumors, Mosquito Small RNAs, More

A Princeton University- and University of Pennsylvania-led team shares insights gleaned from transcriptome sequencing and analyses of canine mammary tumor (CMT) models of human breast carcinoma and tumor development. With the help of RNA sequencing and an analytical pipeline called the "Framework for expression analysis across species" (FREYA), the researchers profiled gene expression patterns and searched for somatic mutations in 22 malignant mammary samples, 41 benign tumor samples, and more than two dozen matched normal samples from dogs spanning 16 different breeds. "Altogether, our study demonstrates the relatedness of human breast cancer and canine mammary tumors at the molecular levels as well as the utility of the CMT model for discerning signals that are obscured in other model systems," they report, adding that canine modeling approach "provides a powerful complement to both human clinical and in vitro studies as well as model organism studies."

Investigators in the US and UK report on a small RNA resource that brings together transposon and virus-related small RNA data for mosquitoes from four medically important species, known for contributing to the spread of pathogenic arboviruses and other human infection contributors. The "Mosquito Small RNA Genomics," or MSRG, collection "captures both somatic and gonadal small RNA expression profiles within mosquito cell cultures," the team writes. The authors used MSRG to follow piwi-interacting RNA (piRNA) biogenesis, for example, while taking a look at piRNA interactions with small-interfering RNA and identifying a conserved piRNA cluster in mosquitoes. "[O]ur data suggests that somatic piRNAs and siRNAs may be an insect vector response to persistent arbovirus infection," they report, noting that additional small RNA data on wild-caught mosquitoes will likely be incorporated into MSRG in the future.

Finally, a team from the University of Illinois Urbana-Champaign, Carnegie Mellon University, and the University of California, Berkeley, presents findings from a tyramide signal amplification (TSA)-seq-based analysis of three-dimensional genome organization, focusing on so-called nuclear speckles or clusters of pre-messenger RNA splicing factor-enriched interchromatin granules. Based on a series of TSA-seq analyses on several human cell lines, the researchers saw apparent ties between nuclear speckle distance and cell type-specific gene expression, along with physical proximity between nuclear speckles and heat shock-related loci. "Our results demonstrate a largely 'hardwired' genome organization with specific genes moving small mean distances relative to speckles during cell differentiation or physiological transition," they write, "suggesting an important role of nuclear speckles in gene expression regulation."

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.