ISSET Seminar Series - Prof. Carlos Lange - University of Alberta

AbstractCornelia de Lange syndrome (CdLS) is a rare congenital disorder characterised by craniofacial features, growth retardation, limb anomalies, and intellectual disability. The condition arises from pathogenic variants in genes encoding cohesin complex components or regulators, most frequently NIPBL. Despite advances in genomic testing, approximately 30% of clinically diagnosed cases remain unresolved, suggesting the presence of non-coding variants. We investigated 10 classical CdLS patients negative for pathogenic variants in NIPBL, SMC1A, SMC3, RAD21, and HDAC8. Genome-wide methylation profiling was performed to identify CdLS-specific epigenetic signatures. Episignature-positive cases underwent trio-based deep sequencing of the entire NIPBL locus while targeted NIPBL RNA sequencing was used to assess splicing. Whole-genome sequencing (WGS) was performed in episignature-negative individuals. Five of ten patients exhibited a positive CdLS episignature in blood, saliva, or skin. Deep sequencing identified de novo deep intronic NIPBL variants in all cases, and two additional variants in episignature-negative patients.

Prof Blumstein in the field, photographed by Emily RenkeyThe story of Prof Dan Blumstein’s decision to share videos of the marmots in the Rocky Mountain Biological Laboratory’s field study on an OnlyFans account called OnlyMarms has captured the world over the last few weeks. 64 years of research into marmots can provide incredible insights into their evolution and socioecology, but the study is as expensive to run as it is valuable — and funding challenges have forced Blumstein, professor of ecology and evolutionary biology at UCLA and Field Chief Editor of Frontiers in Conservation Science, to innovate in new and surprising ways. In this instalment of Frontier Scientists, Blumstein explains to us why this long-running study of yellow-bellied marmots is so important for science, how funding losses are putting it at risk, and how he’s fighting back. What inspired you to become a researcher? I’ve always been interested in nature and spent a lot of time outside — exploring, watching animals, as well as hiking, climbing, and skiing while growing up.