Christian Gilissen

The paper shows inherited protein-truncating variants contribute to developmental disorders through partial gene expression loss, affecting ~20% of children with such variants.

MetaDome now supports GRCh38 alongside GRCh37, adds coordinate lookup, and identifies 52,463 GRCh38 ClinVar missense variants of uncertain significance with uncontradicted pathogenic evidence at homologous Pfam-domain positions.

The paper identifies distinct mechanisms of CNV formation at the human 15q13.3 locus, showing that non-allelic homologous recombination is the primary mechanism, influenced by inversion polymorphisms and population-specific susceptibility.

This paper reanalyzes short-read WGS data and applies long-read WGS to improve genetic diagnosis of inherited retinal disease cases that were previously unresolved.

This study identifies excessive RAS/MAPK pathway activation as a cause of adult-onset motor axonal degeneration in Drosophila, showing that inhibiting the pathway can rescue neurodegenerative phenotypes.

The paper identifies two novel deep-intronic PCDH15 variants in Usher syndrome patients and demonstrates the efficacy of antisense oligonucleotides in correcting their splicing defects.

This study evaluates long-read genome sequencing in rare disease diagnostics, finding high concordance with standard-of-care tests and incremental diagnostic benefits.

The paper uses long-read sequencing to characterize structural variants in 1,019 samples from the 1000 Genomes Project, identifying 167,291 sequence-resolved SVs and highlighting their genomic and functional implications.

The paper examines reproductive and cognitive effects in carriers of recessive pathogenic variants using UK Biobank data, finding fitness effects and reduced cognition in carriers of intellectual disability-associated genes.

The paper develops Paraphase, a HiFi-based method to resolve highly similar paralogous genes, revealing genetic diversity and de novo events in segmental duplications.

The paper demonstrates that HiFi long-read sequencing can detect 93% of clinically relevant variants challenging to identify with short-read sequencing, using 30x coverage and showing potential for cost-effective diagnostic implementation.

The paper identifies de novo and inherited variants in U4 and U6 snRNAs causing retinitis pigmentosa and shows their impact on snRNP biogenesis.

The paper reanalyzes exome sequencing data from rare disease cases to identify previously undetected copy number variants, resulting in diagnoses for 51 families and partial explanations for 34 individuals.

TRGT-denovo accurately detects de novo tandem repeat mutations in family trios, reducing false positives and improving precision compared to genotype-based methods.

This study reanalyzes exome sequencing data from 1,300 IEI patients, finding that systematic reanalysis increases the molecular diagnostic yield from 11.8% to 15.2%.

The paper uses HiFi long-read sequencing to identify genetic variants in undiagnosed rare disease families, finding novel diagnoses in 13% of cases and candidate variants in 4.3%.

The paper identifies variant-specific effects of AFF3 on transcriptome profiles through analysis of patient cohorts and zebrafish models, showing distinct pathophysiological mechanisms for different types of AFF3 variants.

This study evaluates genome sequencing as a primary diagnostic tool for rare diseases, finding it can detect 95% of clinically relevant variants with a 0.3% false negative rate.

The paper introduces a cost-effective smMIPs panel for genetic analysis of RP and LCA, achieving a 56% diagnostic yield comparable to WES.

The paper develops Paraphase, a method using long-read sequencing to accurately determine SMN1 and SMN2 haplotypes and copy numbers, improving silent carrier detection in spinal muscular atrophy.

The paper identifies function-altering de novo mutations in neurodevelopmental disorders by analyzing mutational hotspots across homologous protein domains.

The paper uses smMIPs to sequence MD-associated genes and loci in patients, achieving high coverage and a 38% diagnostic yield.

This study identifies ANKRD11 missense variants as a cause of KBG syndrome by impairing protein stability or transcriptional activity, supporting haploinsufficiency as the underlying mechanism.

DeNovoCNN is a deep learning tool for de novo variant calling in sequencing data, achieving high recall and precision compared to existing methods.

The paper shows inherited CHD3 variants cause Snijders Blok-Campeau syndrome with variable expressivity, overlapping with de novo variants' phenotypes, and suggests reduced penetrance is not due to expression compensation.

The paper identifies de novo mutations as a significant genetic cause of male infertility, finding several candidate genes and an enrichment of loss-of-function and missense mutations in intolerant genes.

The paper analyzes de novo mutations in autism and developmental disorder trios to identify candidate genes and functional networks associated with neurodevelopmental disorders.

The paper investigates family-specific contributions to de novo mutations and finds that stochasticity explains most of the variation.

The paper characterizes the clinical and molecular features of 36 individuals with SETD1B variants, identifying a core phenotype of developmental delay and variable epilepsy, with male predominance and potential sex-linked effects.

This study identifies associations between rare and common genetic variants in the IL-1 pathway and cytokine responses to various stimuli in healthy individuals.