A bone repair gene The protein Sonic Hedgehog, and its encoding gene, SHH , have an essential role in embryonic skeletal formation and brain development. SHH , and the hedgehog pathway, were named for functional studies in fruit flies in the early 1980s. Fruit fly embryos with nonfunctional SHH have bristles that clump into a single patch. The patch of bristles gives the embryo a spiny appearance that resembles a hedgehog. In humans, SHH is responsible for patterning in the central nervous system, such as vertebrae development. Changes in SHH can result in severe brain, skull, and facial defects. New research connects SHH to a critical early function in the repair of major bone injuries. In mice, researchers found increased SHH expression for a brief period following a major bone injury. SHH levels returned to normal after forming a callus, the initial network that connects across a bone break. Engineered mice, unable to GENETICS & GENOMICS IN SOCIETY
produce the Sonic Hedgehog protein, could not form this scaffold and were unable to heal the broken bones. Re- searchers hope this work will lead to new treatments for traf- fic accidents, combat wounds, and cancer-related bone loss. n REFERENCE: Serowoky, M.A., et al. A murine model of large-scale bone regeneration reveals a selective requirement for Sonic Hedgehog. npj Regen Med (2022) 7, 30. DOI: 10.1038/s41536-022-00225-8
Molecular pathway for sneezing Sneezing is a basic respiratory reflex that rids the airway of irritants and pathogens. Many sneezes are caused by allergens like dust or dander entering the nose or throat. Chronic allergy sufferers find some relief from allergy medica- tion, but there is a
Filling in the human genome gaps The Human Genome Project, completed in 2003, produced the first human reference genome. This spawned dramatic advances in sequencing technology and enhanced the understanding of genetic variation. Using the best technologies available then, the reference genome was only about 92% complete. March of 2022 marked the publication of a new and more complete human reference genome that includes complex and highly repetitive regions of DNA that had been notoriously challenging to interpret.
need for other interventions to curtail sneezing. However, until recently, little was known about the molecular process of sneezing to help create new therapeutics. Scientists discovered a neural pathway that seems to lead to sneezing in mice using a new experimental model of sneezing. In the lab, researchers exposed mice to aerosolized histamine (an allergen) and capsaicin (a chemical that gives spicy peppers their burn), both known to cause humans to sneeze. They monitored the mice for audible signs of sneez- ing and also measured muscle movements in the mice. Both histamine and capsaicin caused sneezing in the mice. To determine the neural pathway that induces sneezing, the team turned their attention to a type of sensory neuron in the mouse nose that expresses a receptor called Trpv1. The neurons release a signaling molecule that binds other neurons in the brainstem. These neurons send electrical signals to more neurons that eventually drive the initiation and propaga- tion of a sneeze. Understanding the mechanism of sneezing opens the door to finding therapies that can help control sneezing. More effective treatments for sneezing could help reduce the spread of infectious diseases. n
The Telomere to Telomere (T2T) consortium comprises researchers from multiple universities, the National Human Genome Research Institute (NHGRI), and the National Institutes of Health (NIH). The group used advances in long-read sequencing technology to produce the first ‘gapless’ genome. Long-read sequencing provides the advantage of producing 10,000 base pair reads instead of the much shorter 150 base pair reads generated by earlier short-read technology. The T2T genome has already revealed 151 megabase pairs of new DNA sequences and more than 2 million new human DNA vari- ants, 622 of those in medically relevant genes. The newly discovered sequences are primarily in telomeres located at the ends of chromo- somes or within centromeres, where replicated chromosomes are attached before cell division. Using long-read sequencing technology enabled a better understanding of chromosome architecture and the identification of previously invisible DNA variants. n More details can be found in the Shareable Science blog post: Filling in the gaps of the human genome.
More details can be found in the Shareable Science blog post: Achoo! Sneezing mice reveal molecular pathway that initiates sneezes
REFERENCE: Li., F., et al. Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem. Cell (2021) 184:14, 3762-3773. DOI: 10.1016/j.cell.2021.05.017
REFERENCE: Nurk, S., et al. The complete sequence of a human genome. Science (2022) 376:6588 44-53. DOI: 10.1126/science.abj6987
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