News from Carvalho Lab
PNRI’s Carvalho Lab continues to advance global understanding of rare disease through cutting-edge research on inversions and complex genomic rearrangements.
In June, Dr. Cláudia Carvalho presented her lab’s latest work—Investigating the Origin and Phenotypic Consequences of Inversions and Complex Genomic Rearrangements in Rare Diseases—at RBCC 2025: the 8th Brazilian Meeting of Cytogenetics and Cytogenomics in Brasília. Her talk highlighted how large-scale DNA changes such as inversions may underlie rare conditions that often remain undiagnosed using conventional approaches.
“Every rare disease we help solve teaches us something new about how the genome works—and how we might better diagnose and treat other conditions.”
Cláudia Carvalho, PhD
PNRI Associate Investigator
In April, the Carvalho Lab published a study in Human Genetics and Genomics Advances, the journal of the American Society of Human Genetics. Titled Genome-wide maps of highly-similar intrachromosomal repeats that can mediate ectopic recombination in three human genome assemblies, the research offers a foundational resource for identifying sites in the genome that are prone to structural rearrangements. By mapping these highly similar repeats across multiple genome assemblies, the study sheds light on where recombination errors may occur—offering valuable insights into how complex genomic variants arise and contribute to disease.
Just a few months later, the European Journal of Human Genetics (EJHG) published another Carvalho Lab study: Investigation of a pathogenic inversion in UNC13D and comprehensive analysis of chromosomal inversions across diverse datasets (July 2025). The research explores how structural variants like inversions can disrupt gene function and lead to disease—and how methodological biases in public datasets may obscure the true frequency of these types of DNA changes across populations. Drawing on population-scale resources and international datasets, the team uncovered patterns that may help identify similar pathogenic variants in other undiagnosed patients.
An accompanying editorial in EJHG reflected on the significance of investigating inversions present in the population such as the one affecting UNC13D. These large-scale DNA changes that are notoriously difficult to detect and interpret, and as a result, are often overlooked in clinical settings. Insights from this work not only help to improve rare disease diagnosis but also highlight the need to look for structural variants in families with unresolved genetic conditions.
The Carvalho Lab continues to expand this work through collaborations with clinical partners and efforts to integrate advanced sequencing technologies—pushing the boundaries of what’s possible in structural variant detection and interpretation.
These recent studies were led by first authors Tuğçe Özgümüş, a graduate student at Acibadem University and current member of the Carvalho Lab at PNRI, and Luis Fernandez-Luna, a former PNRI intern now at the University of Oregon. The research was conducted in collaboration with senior scientists Claudia Gonzaga-Jauregui, PhD, at Universidad Nacional Autónoma de México and Zeynep Coban Akdemir, PhD, at UTHealth Houston.
We’re proud to see the Carvalho Lab’s work making an impact on both the global stage and in the scientific literature—driving discovery, diagnosis, and hope for individuals living with rare conditions.
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