Research on diabetes, multiple myeloma, metastatic colorectal cancer, biomarkers for immunotherapy responses, heart health after pediatric cancer and a potential new treatment for chronic myeloid leukemia are highlighted in this spotlight

A large-scale genomic analysis reveals Brazil as one of the most genetically diverse countries on Earth – shaped by centuries of colonization, forced migration, and Indigenous heritage, researchers report. The study, which leveraged newly generated whole-genome sequences of over 2,700 individuals, uncovered more than 8.7 million previously undocumented genetic variants, including those potentially affecting population health. The colonization of Brazil by Europeans from the 15th to 20th centuries resulted in one of the most profound population displacements in history; around five million European settlers and at least five million enslaved Africans were forcibly brought to a region that was home to more than 10 million Indigenous people. As a result, Brazil today is home to exceptional genetic and cultural diversity – it is the most admixed nation globally, hosting over 200 million people descended from these diverse populations.

However, despite this rich and complex genetic heritage, fine-scale studies of Brazil's genetic population structure – which hold implications for health – remain limited. Whole-genome analyses focused on the Brazilian population are largely undone. To fill these critical gaps, Kelly Nunes and colleagues generated whole-genome sequence data from 2,723 individuals across Brazil, capturing a wide range of ethnic, geographic, and cultural backgrounds. Analysis of this data revealed that Brazilian genomes are among the most genetically diverse globally, containing novel haplotypes rooted in Indigenous American, African, and European ancestries. Notably, Nunes et al. uncovered over 8.7 million previously undocumented genetic variants – more than 11% of all variants in the dataset – many of which were absent from major global databases. Some of these variants lie in regulatory and protein-coding regions that may influence traits like fertility, metabolism, and immunity. The authors also identified 36,637 rare and potentially harmful variants that were more common in individuals with African or Indigenous American ancestry.

A research team supported by the National Institutes of Health (NIH) has developed and safely delivered a personalized gene editing therapy to treat an infant with a life-threatening, incurable genetic disease. The infant, who was diagnosed with the rare condition carbamoyl phosphate synthetase 1 (CPS1) deficiency shortly after birth, has responded positively to the treatment. The process, from diagnosis to treatment, took only six months and marks the first time the technology has been successfully deployed to treat a human patient. The technology used in this study was developed using a platform that could be tweaked to treat a wide range of genetic disorders and opens the possibility of creating personalized treatments in other parts of the body.