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Article
Open AccessMap** medically relevant RNA isoform diversity in the aged human frontal cortex with deep long-read RNA-seq
Determining whether the RNA isoforms from medically relevant genes have distinct functions could facilitate direct targeting of RNA isoforms for disease treatment. Here, as a step toward this goal for neurolog...
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Article
Open AccessThe Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores
The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized...
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Article
Curated variation benchmarks for challenging medically relevant autosomal genes
The repetitive nature and complexity of some medically relevant genes poses a challenge for their accurate analysis in a clinical setting. The Genome in a Bottle Consortium has provided variant benchmark sets,...
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Article
Open AccessSystematic analysis of dark and camouflaged genes reveals disease-relevant genes hiding in plain sight
The human genome contains “dark” gene regions that cannot be adequately assembled or aligned using standard short-read sequencing technologies, preventing researchers from identifying mutations within these ge...
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Article
Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype
Corticobasal degeneration (CBD) is a clinically heterogeneous tauopathy, which has overlap** clinicopathologic and genetic characteristics with progressive supranuclear palsy (PSP). This study aimed to eluci...
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Article
Open AccessLong-read sequencing across the C9orf72 ‘GGGGCC’ repeat expansion: implications for clinical use and genetic discovery efforts in human disease
Many neurodegenerative diseases are caused by nucleotide repeat expansions, but most expansions, like the C9orf72 ‘GGGGCC’ (G4C2) repeat that causes approximately 5–7% of all amyotrophic lateral sclerosis (ALS) a...
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Article
Poly(GR) impairs protein translation and stress granule dynamics in C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis
The major genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is a C9orf72 G4C2 repeat expansion1,2. Proposed mechanisms by which the expansion causes c9FTD/ALS include toxicity...
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Article
Open AccessCorrection to: Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer’s disease resilience
The original version of this article [1] unfortunately contained a typographical error. The ‘Alzheimer’s Disease Neuroimaging Initiative’ was erroneously included as ‘Alzheimer’s Disease Neuroimaging Initative...
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An Epigenetic Spin to ALS and FTD
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating and lethal neurodegenerative diseases seen comorbidly in up to 15% of patients. Despite several decades of research, no...
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Article
Open AccessLinkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer’s disease resilience
While age and the APOE ε4 allele are major risk factors for Alzheimer’s disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without ...
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Article
Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease
We previously found C9orf72-associated (c9ALS) and sporadic amyotrophic lateral sclerosis (sALS) brain transcriptomes comprise thousands of defects, among which, some are likely key contributors to ALS pathogenes...
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Article
Open AccessA novel approach for multi-SNP GWAS and its application in Alzheimer’s disease
Genome-wide association studies (GWAS) have effectively identified genetic factors for many diseases. Many diseases, including Alzheimer’s disease (AD), have epistatic causes, requiring more sophisticated anal...
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Article
Open AccessEvaluating the necessity of PCR duplicate removal from next-generation sequencing data and a comparison of approaches
Analyzing next-generation sequencing data is difficult because datasets are large, second generation sequencing platforms have high error rates, and because each position in the target genome (exome, transcrip...
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Article
Open AccessVariants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels
Prostatic Acid Phosphatase (PAP) is an enzyme that is produced primarily in the prostate and functions as a cell growth regulator and potential tumor suppressor. Understanding the genetic regulation of this en...
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Article
Open AccessGenome-wide association study of prolactin levels in blood plasma and cerebrospinal fluid
Prolactin is a polypeptide hormone secreted by the anterior pituitary gland that plays an essential role in lactation, tissue growth, and suppressing apoptosis to increase cell survival. Prolactin serves as a ...
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Article
Open AccessVariants in CCL16 are associated with blood plasma and cerebrospinal fluid CCL16 protein levels
CCL16 is a chemokine predominantly expressed in the liver, but is also found in the blood and brain, and is known to play important roles in immune response and angiogenesis. Little is...
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Article
Open AccessPresenilin E318G variant and Alzheimer’s disease risk: the Cache County study
Alzheimer's disease is the leading cause of dementia in the elderly and the third most common cause of death in the United States. A vast number of genes regulate Alzheimer’s disease, including Presenilin 1 (PSEN...
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Article
Genetic Discoveries in AD Using CSF Amyloid and Tau
The use of cerebrospinal fluid (CSF) levels of Aβ42 and Tau phosphorylated at threonine 181 (pTau181) as endophenotypes for genetic studies of Alzheimer’s disease (AD) has led to successful identification of b...
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Article
Open AccessPAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer
To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The p...
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Article
Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes
By implementing the conditions for orthotopic implantation of different types of human breast tumors, the authors have created a publicly available bank of new mouse models that more faithfully recreate indivi...
