Jacob Otto Kitzman

The paper maps and redesigns the MYBPC3 promoter to enhance expression and treat haploinsufficient hypertrophic cardiomyopathy.

This paper introduces a framework to model haploinsufficiency-mediated human disorders by modulating gene dosage through splicing, demonstrating its application in creating accurate animal models for cardiomyopathies.

The paper uses saturation genome editing to assess the functional impact of RAD51D and XRCC2 variants, showing high accuracy in distinguishing pathogenic from benign variants.

The paper uses MPRAs to assess context-dependent regulatory activity in type 2 diabetes-linked noncoding regions across different promoters and cell types.

This paper maps 6,888 RAD51D variants to identify biochemical functions critical for homologous recombination and olaparib response, revealing key regions and mechanisms of variant impact.

The paper uses MPRA to assess context-dependent activity of transcription start sites, finding that promoter, position, and strand effects influence regulatory element function.

The paper maps the functional effects of MUTYH variants using deep mutational scanning and DNA repair reporters, resolving variants of uncertain significance and identifying risk-associated mutations.

The paper identifies a lipid metabolism defect as a contributor to variable anemia in Diamond Blackfan anemia syndrome using a murine model and transcriptomic analysis.

This study identifies context-specific regulatory effects of metabolic trait-associated variants in human skeletal muscle cells under different conditions.

The paper measures germline mutation rates in a family with MUTYH pathogenic variants, finding elevated C>A mutations in children of affected mothers but not fathers, suggesting maternal-specific mutator effects.

The paper shows HeLa strains differ in Alu retrotransposition efficiency, with distinct mechanisms for SINE RNA mobilization involving ORF2p.

The paper performs population-scale single-nucleus multi-omic profiling of skeletal muscle to identify genetic regulation across cell types and traits.

The paper identifies known and novel splicing-disruptive variants in WT1 exon 9 using high-throughput assays, finding 16 new variants and 19 variants increasing the KTS+/KTS- ratio.

This study benchmarks eight splice variant prediction algorithms using experimental data from massively parallel splicing assays, finding that deep learning models like SpliceAI and Pangolin perform best but challenges remain for exonic variants.

This study uses high-throughput functional assays to reclassify variants of uncertain significance in Lynch Syndrome, improving variant interpretation and clinical outcomes.

The paper develops a cost-effective sequencing assay to detect clonal hematopoiesis and shows that most clonal mutations expand over time in longitudinal samples.

The paper identifies splice-disruptive POU1F1 variants, including synonymous ones, associated with hypopituitarism using high-throughput splicing assays.

The paper maps transcription start sites in human pancreatic islets and identifies functional regulatory elements linked to type 2 diabetes GWAS signals.

The paper uses information theory to analyze chromatin architecture and identifies TF motifs with high chromatin information enrichment, linking them to functional biological variation.

The paper functionally tests MSH2 missense variants to determine their impact on Lynch Syndrome risk, finding most are neutral and providing a comprehensive functional map.

This study identifies 111 genetic loci and 163 risk variants associated with atrial fibrillation using a GWAS of over 1 million individuals.