62 Works

Sporadic pseudohypoparathyroidism type 1B in monozygotic twins: insights into the pathogenesis of methylation defects

Yamato Keidai, Yorihiro Iwasaki, Kanako Iwasaki, Sachiko Honjo, Murat Bastepe & Akihiro Hamasaki
Context: Sporadic pseudohypoparathyroidism type 1B (sporPHP1B) is an imprinting disease without a defined genetic cause, characterized by broad methylation changes in differentially methylated regions (DMRs) of the GNAS gene. Objective: This work aims to provide insights into the causative event leading to the GNAS methylation defects through comprehensive molecular genetic analyses of a pair of female monozygotic twins concordant for sporPHP1B who were conceived naturally i.e., without assisted reproductive techniques. Methods: Using the leukocyte genome...

Agreement rate data set for GENETEX manuscript

David Miller & Sophia Shalhout
Objectives: Clinico-Genomic Data (CGD) acquired through routine clinical practice has the potential to improve our understanding of clinical oncology. However, these data often reside in heterogeneous and semi-structured data, resulting in prolonged time-to-analyses. Materials and Methods: We created GENETEX: an R package and Shiny application for text mining genomic reports from EHR and direct import into REDCap®. Results: GENETEX facilitates the abstraction of CGD from EHR and streamlines capture of structured data into REDCap®. Its...

SnRNA sequencing defines signaling by RBC-derived extracellular vesicles in the murine heart

Nedyalka Valkov, Avash Das, Guoping Li & Saumya Das
Extracellular vesicles (EVs) mediate intercellular signaling by transferring their cargo to recipient cells, but the functional consequences of signaling are not fully appreciated. Red blood cell (RBC)-derived EVs are abundant in circulation and have been implicated in regulating immune responses. Here, we use a transgenic mouse model for fluorescence-based mapping of RBC-EV recipient cells to assess the role of this intercellular signaling mechanism in heart disease. Using fluorescent-based mapping, we detected an increase in RBC-EV-targeted...

RNAseq data from: A novel TNFR2 agonist antibody expands highly potent regulatory T cells

Willem Kuhtreiber
Patients suffering from inflammatory diseases may benefit by enhancing the function of immunosuppressive regulatory T cells (Tregs). Tumor necrosis factor receptor 2 (TNFR2) has emerged as a central control switch on Tregs for maintaining and restoring the immune balance. Here, we characterized a new human TNFR2-directed antibody agonist. We found that the antibody agonist expands Tregs with a cellular phenotype and mechanistic properties of maximally suppressive Tregs. RNA-sequencing and metabolite data showed that the antibody...

Neural signatures of alpha2 adrenergic agonist-induced unconsciousness and awakening by antagonist

Jesus J. Ballesteros, Jessica Briscoe & Yumiko Ishizawa
The dataset provides all necessary raw data to replicate the main analisys and figures in the manuscript.

Data from: Nonlinearities between inhibition and T-type calcium channel activity bidirectionally regulate thalamic oscillations

Adam Lu, Christine Lee, Max Kleiman-Weiner, Brian Truong, Megan Wang, John Huguenard & Mark Beenhakker
Absence seizures result from 3-5 Hz generalized thalamocortical oscillations that depend on highly regulated inhibitory neurotransmission in the thalamus. Efficient reuptake of the inhibitory neurotransmitter GABA is essential, and reuptake failure worsens seizures. Here, we show that blocking GABA transporters (GATs) in acute brain slices containing key parts of the thalamocortical seizure network modulates epileptiform activity. As expected, we found that blocking either GAT1 or GAT3 prolonged oscillations. However, blocking both GATs unexpectedly suppressed oscillations....

Identification of the first Japanese family with PDX1-MODY (MODY4): a novel PDX1 frameshift mutation, clinical characteristics, and implications

Satoshi Yoshiji, Yukio Horikawa, Sodai Kubota, Mayumi Enya, Yorihiro Iwasaki, Yamato Keidai, Megumi Aizawa-Abe, Kanako Iwasaki, Sachiko Honjo, Kazuyoshi Hosomichi, Daisuke Yabe & Akihiro Hamasaki
Context The PDX1 encodes pancreatic and duodenal homeobox, a critical transcription factor for pancreatic β-cell differentiation and maintenance of mature β-cells. Heterozygous loss-of-function mutations cause PDX1-MODY (MODY4). Case description The patient is an 18-year-old lean man who developed diabetes at 16 years of age. Given his early-onset age and leanness, we performed genetic testing. Targeted-next generation sequencing and subsequent Sanger sequencing detected a novel heterozygous frameshift mutation (NM_00209.4:c.218delT. NP_000200.1: p.Leu73Profs*50) in the PDX1 transactivation domain...

Figure e-1.- Effect of APOE alleles on cognitive domain-specific composite measures.

Alberto Serrano-Pozo, Jing Qian, Rebecca Betensky & Bradley Hyman
Supplemental Figure of our original article "Association of APOE Genotype with Heterogeneity of Cognitive Decline Rate in Alzheimer's Disease" published in Neurology showing model 1-based trajectories of cognitive domain-specific composite measures by APOE genotype, as well as the difference of the APOEe2 and APOEe4 groups with respect to the APOEe3/e3 reference group.

Genetic modifiers of Huntington’s disease differentially influence motor and cognitive domains

Jong-Min Lee
Genome-wide association studies (GWAS) of Huntington’s disease (HD) have identified six DNA maintenance gene loci (among others) as modifiers and implicated a two step-mechanism of pathogenesis: somatic instability of the causative HTT CAG repeat with subsequent triggering of neuronal damage. The largest studies have been limited to HD individuals with a rater-estimated age at motor onset. To capitalize on the wealth of phenotypic data in several large HD natural history studies, we have performed algorithmic...

Current status and future strategies for mentoring women in neurology

Christa San Luis Nobleza, Amtul Farheen, Ilena George, Divya Singhal, Regina Troxell, Jyoti Pillai, Logan Schneider, Catherine Lomen-Hoerth, Jennifer Graves & Stefano Sandrone
The American Academy of Neurology's (AAN) 2017 Gender Disparity Report identified improving mentorship as a key intervention to fill the leadership and pay gaps for women in neurology. Here we summarize the literature on mentoring women, provide an outline of ideal components of programs geared toward closing gender gaps, and present a mentoring program for AAN members. The strategies discussed share similarities with those for closing gaps related to race, ethnicity and religion. Developing effective...

Data from: Convergent evolution of phenotypic integration and its alignment with morphological diversification in Carribean Anolis ecomorphs

Jason J. Kolbe, Liam J. Revell, Brian Szekely, & Jonathan B Losos
The adaptive landscape and the G-matrix are keys concepts for understanding how quantitative characters evolve during adaptive radiation. In particular, whether the adaptive landscape can drive convergence of phenotypic integration (i.e., the pattern of phenotypic variation and covariation summarized in the P-matrix) is not well studied. We estimated and compared P for 19 morphological traits in eight species of Caribbean Anolis lizards, finding that similarity in P among species was not correlated with phylogenetic distance....

Data from: Phased whole-genome genetic risk in a family quartet using a major allele reference sequence

Frederick E. Dewey, Rong Chen, Sergio P. Cordero, Kelly E. Ormond, Colleen Caleshu, Konrad J. Karczewski, Michelle Whirl-Carrillo, Matthew T. Wheeler, Joel T. Dudley, Jake T. Byrnes, Omar E. Cornejo, Joshua W. Knowles, Mark Woon, Katrin Sangkuhl, Li Gong, Caroline F. Thorn, Joan M. Hebert, Emidio Capriotti, Sean P. David, Aleksandra Pavlovic, Anne West, Joseph V. Thakuria, Madeline P. Ball, Alexander W. Zaranek, Heidi L. Rehm … & Jake K. Byrnes
Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date...

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