mRNA expression levels of certain genes have shown predictive value for the outcome of cytarabine-treated AML-patients. We hypothesized that genetic variants play a role in the regulation of the transcription of these genes. We studied leukoblasts from 82 patients with acute myeloid leukemia and observed various extent and frequency of differential allelic expression in the CDA, DCK, NT5C2, NT5C3, and TP53 genes. Our attempts to identify the causative regulatory single nucleotide polymorphisms by a bioinformatics approach did not succeed. However, our results indicate that genetic variations are at least in part responsible for the differences in overall expression levels of these genes.
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http://dx.doi.org/10.1124/dmd.108.023184 | DOI Listing |
HGG Adv
January 2025
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA; University Program in Genetics and Genomics, Duke University, Durham, NC, USA; Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. Electronic address:
Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.
View Article and Find Full Text PDFPLoS Biol
January 2025
Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Definitive hematopoietic stem and progenitor cells (HSPCs) arise from a small number of hemogenic endothelial cells (HECs) within the developing embryo. Understanding the origin and ontogeny of HSPCs is of considerable interest and potential therapeutic value. It has been proposed that the murine placenta contains HECs that differentiate into HSPCs.
View Article and Find Full Text PDFClin Pharmacol Ther
January 2025
Department of Pharmacology, Center for Pharmacogenomics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Clopidogrel, an anti-platelet drug, is used to prevent thrombosis after percutaneous coronary intervention. Clopidogrel resistance results in recurring ischemic events, with African Americans (AA) suffering disproportionately. The aim of this study was to discover novel biomarkers of clopidogrel resistance in African Americans using genome and transcriptome data.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Introduction: Traditional multivariate methods for neuroimaging studies overlook the interdependent relationship between brain features. This study addresses this gap by analyzing relative brain volumetric patterns to capture how Alzheimer's disease (AD) and genetics influence brain structure along the disease continuum.
Methods: This study analyzed data from participants across the AD continuum from the Alzheimer's and Families (ALFA) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies.
Primary cilia play a pivotal role in cellular signaling and development and disruptions in ciliary form and/or function leads to human ciliopathies. Here, we examine the role of , a key component of the intraflagellar transport-A complex, in mouse forebrain development using a null allele. Our findings reveal significant microcephaly in homozygous mutants is caused by disrupted neural progenitor proliferation and differentiation.
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