The week’s most astounding developments from the neobiological frontier.

May 11, 2023

The pangenome: A human genome for everyone

A massive collaboration involving hundreds of laboratories led by researchers at the University of Tennessee Health Science Center in Memphis, Heinrich Heine University in Düsseldorf, Germany, Yale University School of Medicine in New Haven, Connecticut, the Dana-Farber Cancer Institute in Boston, and the University of California, Santa Cruz announced a major breakthrough this week. The so-called Human Pangenome Reference Consortium has sequenced, annotated, and compared DNA from a diverse group of people, in an effort to construct the most accurate reference human genome ever produced. The traditional human genome, a first version of which was solved more than 20 years ago, offers researchers a single linear sequence of DNA. The new pangenome captures variation hotspots within human genes to better reflect our diversity at the biomolecular level. Diversity is reflected at a macroscopic level too, with the pangenome constructed from the sequenced DNA of 47 people, both men and women, from around the world. The result is a richer, meatier understanding of the genetic diversity of the whole human species. The collaboration plans to eventually expand the number of genomes used to 350 people, and they suggest this approach could also be used to capture the genetic diversity of other species and generate a pangenome reference for them. Nature

The anatomy of a diverse human gene is shown in this “sequence tube map” representation of the human HLA-A gene. The graph shows how this important immune system gene is one of the most highly variable in the human body. Each colored line connects pieces of DNA and spells out a particular version of the gene. Thick lines represent more common versions. Diverging lines represent different gene sequences between people, and converging lines are where people’s versions of the genes match. Courtesy Adam M. Novak

Physiological effects of gender inequality on women’s brains

Researchers at the Pontifical Catholic University of Chile in Santiago examined brain structures based on 7,876 MRI scans of healthy men and women from 29 countries. Comparing their neuroanatomy to countywide measures of gender inequality, they conclude that women living in nations with relatively high gender inequality have thinner cortical structures in the right hemispheres of their brains compared to men. Reduced cortical thickness has been observed in aging and in various neuro-degenerative disorders, and it has been tied to depression. Women in countries with relatively high gender equality, on the other hand, showed no significant differences in cortical thickness with their fellow countrymen. The results highlight the role of the environment in determining brain differences between women and men, the researchers write, and suggest a potential link between gender inequality, mental health problems, and reduced academic performance. PNAS

Crosstalk between gut microbiome and cellular senescence in aging

Two well-known physiological changes associated with aging are the accumulation of senescent cells in tissues and alterations to the composition of the gut microbiome—though nobody has known how the two phenomena may be related. Now researchers at Osaka University in Suita, Japan, have shown in aging mice that commensal bacteria in the gut gradually induce cellular senescence in antibody-producing B cells residing there. This alters the diversity of immunoglobulin A antibodies produced in the gut that target bacteria and lowers their overall levels. That slowly changes the composition of gut microbiota with age, the researchers write, “opening up possibilities for their control.” Nature Cell Biology

Certain types of genetic screening would be cost effective for U.S. adults

One of the big promises of the genomic revolution was always that DNA testing could identify people at high risk of genetic diseases so that they could receive interventions early on and better treat or entirely prevent those conditions. In a sign that this promise is finally coming to fruition, doctors at Vanderbilt University Medical Center in Nashville have modeled the cost and benefit of screening U.S. adults for three life-threatening illnesses: Lynch syndrome, hereditary breast and ovarian cancer, and familial hypercholesterolemia. They found enough evidence to suggest that routine testing of adults under the age of 40 for these three diseases would be cost effective because the testing costs are relatively low and people who test positive would have access to interventions that could prevent the diseases, improve their outcomes, and save their lives. Annals of Internal Medicine

Most experts believe in genetic screening for newborns

Doctors at Massachusetts Hospital for Children in Boston surveyed 238 rare disease experts, including each director of all 144 accredited genetics programs in the United States. Asking them about genomic sequencing for newborns, the doctors found overwhelming support among these experts, especially when it comes to screening for metabolic and endocrine diseases for which there are no good biomarkers. Some 87.9 percent of those polled agreed that genomic sequencing for treatable genetic conditions should be available to all newborns, and the survey identified a number of high priority genes that newborns should be screened for. It seems like such a no-brainer that we wonder: Who are the 12.1 percent naysayers, and what is motivating them to say no? JAMA Network Open

Retinal tissue like you’ve never seen

A stunning microscope image of a retina-like “organoid” tissue grown in the laboratory from human pluripotent stem cells promises to unlock many of the secrets of the human retina. The image is part of a toolkit being produced by researchers at ETH Zürich, the University of Basel, and the University of Zürich in Switzerland to visualize the spatial arrangements and patterning of neurons, gene expression, and the fate of cells in the retina, a tissue which contains the photoreceptors that enable our vision and is involved in a number of different forms of blindness. Nature Biotechnology

A retinal organoid with different colors illuminating various tissue structures. Courtesy Wahle et al. Nature Biotechnology 2023