Petr Danecek

Incompletely penetrant protein-truncating variants confer developmental disorder risk through partial reductions in gene expression

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

Imputation of fluid intelligence scores reduces ascertainment bias and increases power for analyses of common and rare variants

The paper imputes fluid intelligence scores in a large cohort, reducing ascertainment bias and increasing power to detect genetic associations with common and rare variants.

The differential effects of common and rare genetic variants on cognitive performance across development

The paper examines how common and rare genetic variants affect cognitive performance across childhood and adolescence, finding age-related changes in their effects and differences in their impact across the phenotype distribution.

Substantial role of rare inherited variation in individuals with developmental disorders

The paper investigates the role of rare inherited coding variants in developmental disorders by analyzing family and case/control data, finding significant burdens of damaging variants and estimating their population attributable risk.

De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders

Mostly de novo variants in an 18 bp constrained region of U4 snRNA gene RNU4-2 cause a syndromic neurodevelopmental disorder, estimated to explain 0.41% of cases.

Deciphering the role of germline complex de novo structural variations in rare disorders

This study identifies de novo structural variants in a large cohort of rare disease patients, highlighting their prevalence and potential pathogenicity.

Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions

This study investigates how common genetic variants contribute to risk for rare neurodevelopmental conditions and examines indirect genetic effects through parental non-transmitted alleles.

Detection and characterisation of copy number variants from exome sequencing in the DDD study

The paper evaluates CNV detection from exome sequencing in the DDD study, finding it has higher sensitivity than low-resolution CMA and comparable sensitivity to exon-resolution CMA.

Federated analysis of the contribution of recessive coding variants to 29,745 developmental disorder patients from diverse populations

The paper quantifies the contribution of recessive coding variants to developmental disorders in diverse populations, identifying novel genes and highlighting challenges in interpreting missense variants.

Effects of somatic mutations on cellular differentiation in iPSC models of neurodevelopment

This study investigates how somatic mutations affect dopaminergic neuron differentiation in iPSCs, finding that deleterious mutations in key genes like BCOR are linked to differentiation failure and altered proliferation.

Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells

The paper analyzes genomic variation in hiPSCs derived from skin and blood, finding high mutation rates in fibroblast-derived lines and frequent BCOR mutations in blood-derived lines.

Optimising diagnostic yield in highly penetrant genomic disease

The paper reports diagnostic outcomes from a large-scale genomic study of developmental disorders, identifying factors that influence diagnostic success.

Genetic and chemotherapeutic causes of germline hypermutation

The paper identifies genetic and chemotherapeutic causes of germline hypermutation by analyzing genome-wide sequences of families with rare genetic diseases.

Detecting cryptic clinically-relevant structural variation in exome sequencing data increases diagnostic yield for developmental disorders

InDelible detects cryptic structural variants in exome sequencing data, improving diagnostic yield for developmental disorders by identifying variants missed by standard methods.

Non-coding variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms

The paper identifies non-coding variants upstream of MEF2C causing severe developmental disorder through three distinct loss-of-function mechanisms, showing their diagnostic importance in existing exome datasets.

HTSlib - C library for reading/writing high-throughput sequencing data

HTSlib provides a C library for efficient programmatic access to high-throughput sequencing data formats, with performance improvements and new features.

Population-scale proteome variation in human induced pluripotent stem cells

The paper characterizes proteome variation across 202 human iPSC lines, identifies 700 pQTLs, and links pQTLs to disease-associated GWAS variants.

Integrating healthcare and research genetic data empowers the discovery of 28 novel developmental disorders

The paper integrates healthcare and research exome sequences to identify 28 novel developmental disorder-associated genes using a simulation-based statistical test.

Insights into human genetic variation and population history from 929 diverse genomes

This study presents 929 high-coverage human genome sequences from 54 populations, revealing new insights into genetic variation and population history.

Single-cell RNA-seq of differentiating iPS cells reveals dynamic genetic effects on gene expression

The paper uses single-cell RNA-seq of differentiating iPS cells from 125 donors to identify expression quantitative trait loci influencing gene expression during endoderm differentiation.

Exome-wide assessment of the functional impact and pathogenicity of multi-nucleotide mutations

The paper identifies 299 new genes associated with developmental disorders using exome data from 31,058 trios and finds many more likely remain undiscovered.

Contribution of Retrotransposition to Developmental Disorders

The paper identifies retrotransposition events in developmental disorders using exome sequencing data from the DDD study and shows their evolutionary constraints.

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

The paper identifies 9 novel genetic loci, including low-frequency variants in TP53, associated with head circumference and intracranial volume in up to 46,000 individuals.

Very low depth whole genome sequencing in complex trait association studies

This study evaluates very low depth whole genome sequencing for complex trait association studies, showing it can efficiently discover association signals comparable to imputed GWAS chip designs.

Cardelino: Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants

Cardelino integrates whole exomes and single-cell transcriptomes to identify clone-of-origin and reveal phenotypic impacts of somatic variants in human fibroblasts.

Narrow-sense heritability estimation of complex traits using identity-by-descent information.

This paper estimates narrow-sense heritability using identity-by-descent information in unrelated individuals and finds that IBD-based methods can capture rare variant contributions but are affected by stratification.

Multiple laboratory mouse reference genomes define strain specific haplotypes and novel functional loci

The paper presents full-length de novo genome assemblies for 16 inbred mouse strains, identifying strain-specific haplotypes and novel functional loci, including a large unannotated gene with potential developmental roles.

Population Genotype Calling from Low-coverage Sequencing Data

Ref-Reveel improves genotype calling accuracy and efficiency from low-coverage sequencing data by jointly analyzing large cohorts and using generated genotypes as references for new datasets.

Continuity and admixture in the last five millennia of Levantine history from ancient Canaanite and present-day Lebanese genome sequences

This study analyzes ancient and modern genomes from the Levant to trace genetic continuity and admixture over five millennia, finding Canaanite-related ancestry and later Eurasian influences.

BCFtools/csq: Haplotype-aware variant consequences

BCFtools/csq improves variant consequence prediction by considering haplotype context, correcting 501 compound variants in 1000 Genomes data with faster performance.