BEGIN:VCALENDAR VERSION:2.0 PRODID:-//132.216.98.100//NONSGML kigkonsult.se iCalcreator 2.20.4// BEGIN:VEVENT UID:20250805T145128EDT-3056mBvR2U@132.216.98.100 DTSTAMP:20250805T185128Z DESCRIPTION:Paul Valdmanis will present\, “Identifying dynamics of tandem r epeat expansions in human evolution and neurodegenerative disease using lo ng-read sequencing”. \n\nRegistration available here.\n\nSpeaker: Paul Val dmanis\, PhD\n\nAssistant Professor\, Department of Medicine\, Division of Medical Genetics\, University of Washington\n\nAbstract: Over 40 tandem r epeats undergo expansion events that lead to neurological disease. This nu mber is likely an underestimate as many repeats are difficult to amplify u sing existing short read sequencing approaches. Through the use of long-re ad sequencing\, we identified a 69 bp intronic variable number tandem repe at (VNTR) in WD repeat domain 7 (WDR7). The VNTR is expanded in a family w ith Amyotrophic Lateral Sclerosis (ALS) and exhibits significantly higher repeat copy number in three independent cohorts of individuals with sporad ic ALS compared with matched controls\, suggesting that it plays a role in modifying susceptibility to ALS. Each 69 bp repeat motif forms a stem-loo p structure with the potential to produce microRNAs\, and the repeat RNA c an aggregate when expressed in cells – a common hallmark of neurodegenerat ive disease pathology. We performed multiplexed barcoded PacBio long-read sequencing to resolve the complete internal structure of the WDR7 repeat i n 288 geographically diverse individuals. We found striking variability in both repeat length and internal nucleotide composition. Some of the 69 bp repeat motifs are specifically present or absent in certain geographic po pulations\, and we identified common repeat motifs in both Denisovan and N eanderthal genomes. We found that the repeat expands in the 3′-5′ directio n\, in groups of two repeat units. Extending this analysis to characterize VNTRs genome-wide\, we identified several VNTRs that can differ in length (by up to 20 kb) amongst individuals and geographical super-populations a nd repeats that exhibit substantial diversity in internal sequence composi tion of the repeat. By characterizing the WDR7 VNTR in ALS\, we identify f eatures associated with repeat expansion dynamics\, the mechanistic conseq uences of repeat expansions to ALS susceptibility\, and the structure of r epeats in geographically diverse populations that can precipitate expansio n events.\n\nBio: Paul Valdmanis is an Assistant Professor in the Departme nt of Medicine\, Division of Medical Genetics and an Adjunct Assistant Pro fessor in the Department of Genome Sciences at the University of Washingto n in Seattle\, Washington. His research laboratory works to identify genet ic and molecular contributions to neurodegenerative disease including Amyo trophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD) with a partic ular emphasis on long-read sequencing of tandem repeat expansions. His gro up then uses gene therapy methods for therapeutic intervention in ALS and AD. Dr. Valdmanis has worked extensively to determine the genetic basis of neurodegenerative disease during his doctoral studies at ĢƵ Universit y in the Department of Human Genetics. He has made seminal discoveries inc luding the first identification of mutations in TDP-43 in patients with AL S\, mutations in KIAA0196 (Strumpellin) in patients with Hereditary Spasti c Paraplegia and an RNF170 mutation in a novel form of Autosomal Dominant Sensory Ataxia. Dr. Valdmanis completed his postdoctoral studies in the la boratory of Mark Kay at Stanford University. There he optimized methods to fine-tune gene regulation through use of microRNAs and determined the con sequences of aberrant microRNA activation in lung and liver cancer. Furthe rmore\, he has established gene therapy methods to safely and efficiently reduce target genes through use of adeno-associated viral delivery of smal l hairpin RNAs and identified a mechanism by which small hairpin RNAs comp ete with endogenous microRNAs. Dr. Valdmanis has published over 50 manuscr ipts\, including 21 for which he is the first or co-first author. His work has been cited over 7000 times with an H-index of 28. He is the recipient of a Banting postdoctoral fellowship\, a Bisby postdoctoral fellowship\, a Governor General’s Gold Medal at ĢƵ and a Robert F. Schoe ni Award for Research from Ann Arbor Active Against ALS.\n\n\nSupported by the generosity of the Killam Trusts \, The Neuro’s Killam Seminar series hosts outstanding guest speakers whose research is of interest to the scie ntific community at The Neuro and ĢƵ.\n DTSTART:20220104T210000Z DTEND:20220104T220000Z SUMMARY:Killam Seminar Series presents “Identifying dynamics of tandem repe at expansions in human evolution and neurodegenerative disease using long- read sequencing” URL:/neuro/channels/event/killam-seminar-series-presen ts-identifying-dynamics-tandem-repeat-expansions-human-evolution-and-33525 0 END:VEVENT END:VCALENDAR