James F. Gusella

The paper investigates how POGZ loss-of-function affects transcription factor binding and gene expression in neurons, revealing shared molecular changes with other NDD-related genes.

This study investigates the role of WWOX in DNA damage and somatic instability in Huntington's disease, finding that WWOX promotes DNA damage but not CAG repeat instability.

TRACE is an open-source software that quantifies somatic instability of tandem repeats using capillary electrophoresis data, providing accessible tools for analyzing repeat expansion.

This paper investigates the protective effect of the LIG1 K845N variant in Huntington's disease by showing it increases ligase fidelity and suppresses somatic CAG repeat expansion.

The paper investigates the functional role of recursive splicing in CADM2, showing that its deletion leads to altered gene expression and behavioral changes in neurodevelopmental disorders.

The paper identifies genetic modifiers of Huntington's disease somatic CAG repeat instability using CRISPR-Cas9 in HD knock-in mice, revealing new therapeutic targets.

This paper resolves ring chromosomes, Robertsonian translocations, and complex structural variants using long-read sequencing and telomere-to-telomere assembly, revealing breakpoint structures and methylation changes.

The paper identifies genetic modifiers of somatic CAG expansion and clinical phenotypes in Huntington's disease, revealing shared and tissue-specific effects on disease timing and pathogenic processes.

This study shows splice modulators like branaplam reduce HTT CAG repeat expansion by affecting PMS1 expression, suggesting PMS1 as a new therapeutic target for Huntington's disease.

The paper identifies transcriptional upregulation of glutamate receptors and downregulation of oxidative phosphorylation in an ovine HD model before neuronal loss and motor symptoms.

This study shows that CHD8 suppression reduces H3K36me3 levels and alters alternative splicing of ~2000 genes, linking CHD8 to RNA processing and ASD.

The paper investigates the effects of MEF2C mutations and chromatin structural variants on transcriptional and functional outcomes in neuronal models, revealing differential impacts based on mutation type and chromatin topology.

This study identifies molecular and functional changes in mouse and human models of 16p11.2 reciprocal genomic disorder, revealing context-specific disruptions in energy metabolism, RNA processing, and neuronal development.

The paper identifies a tandem hexamer repeat in TCERG1 that modifies age at motor onset in Huntington's disease, explaining the effect of a previously associated SNP.

This study identifies 114 genome-wide significant rare CNV-disease associations across 30 neurological disorders, revealing 38 novel triplosensitive genes and developing a model to predict dosage sensitivity.

The paper identifies MAPK3 as a driver gene in 16p11.2 deletion-associated neurodevelopmental disorders, showing haplotype-specific expression and cis-regulatory enhancer SNPs contribute to variable phenotypes.

The paper identifies cell type specific driver genes in autism-associated copy number loci using cerebral organoids and validates findings with CRISPR/Cas9-edited mosaic organoids.

The paper identifies FAN1 nuclease activity as a modifier of CAG expansion and age at onset in Huntington's disease through exome sequencing and functional validation.

The paper investigates how dystonia-specific mutations in THAP1 affect gene transcription related to neurodevelopment and myelin in iPSC-derived neural cells and mouse models.

This study examines the prevalence, timing, and functional impact of psychiatric, cognitive, and motor symptoms in Huntington's disease gene carriers using clinical data from a large cohort.

This paper develops a piggyBac transposon system for CRISPR library delivery to human iPSCs, enabling scalable mutational modeling of genes and variants.

The paper investigates genetic risk factors for psychiatric and cognitive symptoms in Huntington’s Disease using polygenic risk scores and finds associations between specific psychiatric risk scores and corresponding symptoms.

This study investigates the developmental effects of hypomorphic mutations in the mouse HD gene orthologue, revealing varying degrees of lethality and developmental abnormalities depending on mutation severity.

This study shows that the length of uninterrupted CAG repeats, not the encoded polyglutamine segment, determines Huntington's disease onset, and DNA maintenance genes modify this process.