Elizabeth Blue

A high-resolution human pangenome structural variant resource for improved disease association

The paper constructs a high-resolution human pangenome structural variant resource, identifies disease-associated SVs, and demonstrates its utility in filtering variants from probands and associating SVs with traits in a large cohort.

Long-read transcriptome analysis using IsoRanker for identifying pathogenic variants in Mendelian conditions

IsoRanker uses long-read transcriptomics to prioritize non-coding variants in Mendelian conditions by detecting expression outliers, allelic imbalance, and NMD, leading to the identification of pathogenic variants in one individual.

Uncovering Phenotypic Expansion in AXIN2-Related Disorders Using Precision Animal Modeling

The paper identifies novel AXIN2 variants causing expanded phenotypes in humans and validates their pathogenicity using human, mouse, and fly models.

Polygenic risk scores for incident dementia in the Multi-Ethnic Study of Atherosclerosis

The paper evaluates polygenic risk scores for dementia prediction in diverse populations, finding that a model with fewer SNPs outperforms one with more SNPs in multiple ethnic groups.

Phenotype-Specific Recalibration of MAVE Data Enables Repurposing of BAP1 Functional Assays for Kury-Isidor Syndrome

The paper recalibrates BAP1 MAVE data for different disease phenotypes to enable accurate variant classification across related disorders.

Genome-wide detection and clinical prioritization of tandem repeat outliers using long-read sequencing

The paper develops TRoLR, a pipeline using long-read sequencing to detect and prioritize pathogenic tandem repeat expansions in diverse populations, identifying known and novel expansions with clinical relevance.

Multiple-testing corrections in case-control studies using identity-by-descent segments

This paper proposes a method to correct for multiple testing in IBD mapping for case-control studies, identifies six genome-wide significant AD risk loci, and shows positive selection can confound results.

An optimized variant prioritization process for rare disease diagnostics: recommendations for Exomiser and Genomiser

This paper optimizes variant prioritization parameters for Exomiser and Genomiser to improve diagnostic yield in rare disease cases using WES and WGS data.

Heterozygous variants in PLCG1 affect hearing, vision, cardiac, and immune function

The paper reports seven individuals with PLCG1 variants causing hearing, vision, cardiac, and immune issues, and shows these variants have gain-of-function effects in Drosophila models.

Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations

The paper presents a joint genomic analysis of UDN patients using whole genome sequencing and new statistical methods to prioritize disease genes, revealing new disease associations and releasing a software tool for cohort analysis.

Genetic risk implicating endolysosomal network genes correlates with endolysosomal dysfunction across neural cell types in Alzheimer's disease

This study shows that genetic risk variants in endolysosomal network genes correlate with endolysosomal dysfunction in neural cells in Alzheimer's disease.

Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition

Pooling Fiber-seq gDNA with concatenated MAS-Seq cDNA in one PacBio run gives phased genome, methylome, chromatin, and transcriptome, exposing four gene disruptions from one X;13 translocation.

Association of Common and Rare Variants with Alzheimer's Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer's Disease Sequencing Project

The paper investigates the association of common and rare variants with Alzheimer's Disease in 13,371 diverse individuals using whole-genome sequencing, identifying significant genetic loci and population-specific associations.

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.

Key variants via Alzheimer's Disease Sequencing Project whole genome sequence data

This study uses whole genome sequence data from the ADSP to identify 17 significant variants in five genomic regions associated with Alzheimer's disease.

Full-length isoform sequencing for resolving the molecular basis of Charcot-Marie-Tooth 2A

The paper uses full-length isoform sequencing to identify a splicing defect in MFN2 causing CMT2A in a patient with undiagnosed neuropathy.

Transcriptomically unique endolysosomal and homeostatic microglia populations in Alzheimer's disease and aged human brain

The paper identifies transcriptomically distinct microglia populations in Alzheimer's disease and aged human brains using single-nucleus RNA-seq and trajectory inference.

PRDM1 DNA-binding zinc finger domain is required for normal limb development and is disrupted in Split Hand/Foot Malformation

The paper identifies PRDM1 variants causing Split Hand/Foot Malformation and shows their functional impact on limb development through zebrafish experiments and gene expression analysis.

Precision medicine for developmental and epileptic encephalopathies in Africa: strategies for a resource-limited setting.

The paper identifies genetic variants in South African children with developmental and epileptic encephalopathies and proposes a 'Think-Genetics' strategy for early genetic diagnosis in resource-limited settings.

FAVOR: Functional Annotation of Variants Online Resource and Annotator for Variation across the Human Genome

FAVOR provides an online resource and tool for functional annotation of variants from whole genome sequencing studies to aid in disease gene prioritization.

Genetic Examination of Hematological Parameters in SARS-CoV-2 Infection and COVID-19

This study examines the genetic links between baseline hematological parameters and risk of SARS-CoV-2 infection and severe COVID-19 using Mendelian randomization and GWAS data.

Centers for Mendelian Genomics: A decade of facilitating gene discovery

The paper describes the role of the Centers for Mendelian Genomics in advancing gene discovery through data sharing, collaboration, and resource development over the past decade.

Leveraging TOPMed Imputation Server and Constructing a Cohort-Specific Imputation Reference Panel to Enhance Genotype Imputation among Cystic Fibrosis Patients

The paper improves genotype imputation for CF patients using the TOPMed reference panel and a CF-specific imputation panel, enhancing marker coverage and PRS accuracy.

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain

The paper identifies de novo PRKAR1B variants in six individuals with neurodevelopmental disorder, autism, apraxia, and reduced pain sensitivity.

De novo EIF2AK1 and EIF2AK2 variants are associated with developmental delay, leukoencephalopathy, and neurologic decompensation

The paper identifies de novo variants in EIF2AK1 and EIF2AK2 associated with neurodevelopmental disorders and leukoencephalopathy, showing similar pathogenic mechanisms to CACH/VWM.