Harrison Brand

Multi-omics in the All Of Us Research Program expands mapping genetic mechanisms in health and disease

The paper reports on the All of Us multi-omics cohort, identifying 182,246 QTLs and demonstrating rare variant effects across proteomic and transcriptomic data.

Tandem repeat variation shapes immune cell type-specific gene expression

The paper identifies immune cell type-specific gene expression regulated by tandem repeats using multi-omics data from large cohorts.

Characterization of de novo structural variants in trios with orofacial clefts

This study identifies de novo structural variants in individuals with orofacial clefts and finds they contribute to genetic risk, with some variants disrupting known risk genes and suggesting new candidate genes.

Genomic Research as a Critical Pathway to Diagnosis for Individuals with Rare Disease

The Rare Genomes Project provides remote genomic sequencing to rare disease families, achieving a 23.3% diagnostic solve rate and highlighting the role of research in overcoming clinical diagnostic barriers.

Rare variation illuminates the distinct and pleiotropic genetic architecture of autism across neuropsychiatric traits

The paper identifies 253 autism-associated genes using rare variation from 62,429 individuals and finds pleiotropy across physiological systems and developmental disorders.

Structural Variant Imputation in Samoans Using a Population-Specific Reference Panel

The paper imputes structural variants and SNVs in Samoans using a population-specific reference panel, showing improved imputation performance compared to multi-ancestry panels.

Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing

This study evaluates the diagnostic yield of short-read and long-read sequencing in rare diseases, finding limited added value from long-read sequencing despite increased variant discovery.

Comprehensive analysis of de novo variants across 2,497 orofacial cleft trios reveals novel genetic drivers of disease

This study identifies novel genetic drivers of orofacial clefts by analyzing de novo variants in 2,497 trios and integrating findings across subtypes and syndromic status.

NeuroDev: etiology and experience of neurodevelopmental disorders in Kenya and South Africa

The paper presents genetic and phenotypic data from 521 children with neurodevelopmental disorders in Kenya and South Africa, highlighting high genetic diagnosis rates linked to environmental risk factors.

Integrating 730,947 exome sequences with clinical literature improves gene discovery

gnomAD v4 (730,947 exomes) brings LOFTEE-2 loss-of-function annotation (0.90 precision, strict mode), missense-aware constraint, and LLM-mined literature evidence combined with constraint to rank disease genes.

Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy

The paper identifies rare variants in PRKCI as a novel cause of Van der Woude syndrome and other peridermopathy features through clinical and functional analyses.

Distinguishing syndromic and nonsyndromic cleft palate through analysis of protein-altering de novo variants in 816 trios

The paper identifies protein-altering de novo variants in CP probands, finding higher enrichment in syndromic cases and distinct biological enrichments in single-cell RNA sequencing datasets.

Rare germline structural variants increase risk for pediatric solid tumors

This study identifies rare germline structural variants as risk factors for pediatric solid tumors, particularly neuroblastoma, by analyzing genome sequencing data from affected children and controls.

Resolution of ring chromosomes, Robertsonian translocations, and complex structural variants from long-read sequencing and telomere-to-telomere assembly

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.

Defining a tandem repeat catalog and variation clusters for genome-wide analyses

The paper introduces a new TR catalog, TRExplorer v1.0, containing 4.86 million loci, designed for both short-read and long-read analyses and includes variation clusters identified using long-read HiFi data.

Genome-wide study of gene-by-sex interactions identifies risks for cleft palate

The paper identifies sex-specific genetic risks for cleft palate through genome-wide gene-by-sex interaction analysis in a trio-based cohort.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes

This study identifies shared and distinct ultra-rare genetic risk factors for epilepsy subtypes using whole-exome sequencing of 20,979 patients and 33,444 controls.

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders

The paper develops a cell type-aware framework to identify non-coding variants in Mendelian disorders by integrating single-cell multi-omic data and applying it to congenital cranial dysinnervation disorders.

A blended genome and exome sequencing method captures genetic variation in an unbiased, high-quality, and cost-effective manner

The paper introduces BGE, a sequencing method that combines low-pass whole genome and deep whole exome data, showing high accuracy and cost-effectiveness for genetic variant discovery.

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing

The paper develops criteria for identifying, sharing, and reporting novel candidate genes in clinical genomic testing to improve diagnostic yield for Mendelian conditions.

A harmonized public resource of deeply sequenced diverse human genomes

The paper harmonizes diverse human genomes from multiple datasets to create a new reference panel with improved variant coverage and population structure analysis.

Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease

The paper detects and classifies copy number variants in exome data from 6,633 families, identifying causal CNVs in 173 families and improving classification standards.

A genome-wide mutational constraint map quantified from variation in 76,156 human genomes

Rare-variant depletion in 1kb windows of 76,156 gnomAD genomes, versus feature-adjusted mutation expectations, marks regulatory elements and outperforms seven alternative scores at flagging functional non-coding variants.

Missense variants affecting the actin-binding domains of PLS3 cause X-linked congenital diaphragmatic hernia and body wall defects

The paper identifies missense variants in PLS3 causing X-linked congenital diaphragmatic hernia and body wall defects through genetic analysis and functional studies.

Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate

This study performs trio-based GWAS to identify genetic risk factors for cleft palate subtypes, finding a genome-wide significant locus and subtype-specific associations.

Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis

This study evaluates genome sequencing's diagnostic yield in a cohort of undiagnosed rare disease patients, finding it solves 29.3% of cases with specific variant types not detectable by exome sequencing.

Phenotype and genetic analysis of data collected within the first year of NeuroDev

The paper presents phenotype and genetic analysis of 206 children with neurodevelopmental disorders from Kenya and South Africa, identifying pathogenic variants in 17% of South African and 38% of Kenyan cases.

Rare variants found in clinical gene panels illuminate the genetic and allelic architecture of orofacial clefting

The paper estimates the diagnostic yield of sequencing 418 genes in OFC cases and controls, finding a higher prevalence of likely pathogenic variants in cases.

High coverage whole genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios

The paper presents a high coverage whole genome sequencing resource of 3,202 samples, including 602 trios, generated from the expanded 1000 Genomes Project.