In this article we examine the history of the production of microarray technologies and their role in constructing and operationalizing views of human genetic difference in contemporary genomics. Rather than the "turn to difference" emerging as a post-Human Genome Project (HGP) phenomenon, interest in individual and group differences was a central, motivating concept in human genetics throughout the twentieth century. This interest was entwined with efforts to develop polymorphic "genetic markers" for studying human traits and diseases. We trace the technological, methodological and conceptual strategies in the late twentieth century that established single nucleotide polymorphisms (SNPs) as key focal points for locating difference in the genome. By embedding SNPs in microarrays, researchers created a technology that they used to catalog and assess human genetic variation. In the process of making genetic markers and array-based technologies to track variation, scientists also made commitments to ways of describing, cataloging and "knowing" human genetic differences that refracted difference through a continental geographic lens. We show how difference came to matter in both senses of the term: difference was made salient to, and inscribed on, genetic matter(s), as a result of the decisions, assessments and choices of collaborative and hybrid research collectives in medical genomics research.
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http://dx.doi.org/10.1007/s10739-018-9543-x | DOI Listing |
J Am Chem Soc
January 2025
Department of Chemistry, University of California, Riverside, California 92521-0403, United States.
Pseudouridine (Ψ) is the most abundant RNA modification in nature; however, not much is known about the biological functions of this modified nucleoside. Employing an unbiased quantitative proteomics method, we identified multiple candidate reader proteins of Ψ in RNA, including a cytoskeletal protein profilin-1 (PFN1). We demonstrated that PFN1 binds directly and selectively to Ψ-containing RNA.
View Article and Find Full Text PDFJ Med Virol
January 2025
Radiology department, Tianjin Fifth Central Hospital, Tianjin, China.
To evaluate the performance of three rapid influenza diagnostic tests (RIDTs) for detecting influenza A and B viruses compared to RT-PCR. A total of 291 subjects with acute respiratory infections were enrolled. Respiratory specimens were collected and tested for influenza A and B viruses using three RIDTs.
View Article and Find Full Text PDFMol Inform
January 2025
Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Corrensstr. 48, 48149, Muenster, Germany.
Primary carnitine deficiency (PCD) is a rare autosomal recessive genetic disorder caused by missense mutations in the SLC22A5 gene encoding the organic carnitine transporter novel type 2 (OCTN2). This study investigates the structural consequences of PCD-causing mutations, focusing on the N32S variant. Using an alpha-fold model, molecular dynamics simulations reveal altered interactions and dynamics suggesting potential mechanistic changes in carnitine transport.
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March 2025
Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.
T cell-based immunotherapies targeting antigens on tumor cells have shown efficacy as anti-cancer treatments. While neoantigens are created by somatic mutations acquired during tumorigenesis, allogeneic stem cell transplantation as treatment for hematological malignancies exploits minor histocompatibility antigens encoded by genetic differences between patients and donors. Screening methods to predict neoantigens and minor histocompatibility antigens typically consider only conventional antigens created by nonsynonymous mutations or polymorphisms coding for amino acid changes in canonical open reading frames (ORFs).
View Article and Find Full Text PDFiScience
January 2025
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.
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