We present a multifactorial, multistep approach called genomic convergence that combines gene expression with genomic linkage analysis to identify and prioritize candidate susceptibility genes for Parkinson's disease (PD). To initiate this process, we used serial analysis of gene expression (SAGE) to identify genes expressed in two normal substantia nigras (SN) and adjacent midbrain tissue. This identified over 3700 transcripts, including the three most abundant SAGE tags, which did not correspond to any known genes or ESTs. We developed high-throughput bioinformatics methods to map the genes corresponding to these tags and identified 402 SN genes that lay within five large genomic linkage regions, previously identified in 174 multiplex PD families. These genes represent excellent candidates for PD susceptibility alleles and further genomic convergence and analyses.
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Cell Death Differ
December 2024
Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, D.C., USA.
Germline inactivating mutations of the SLC25A1 gene contribute to various human disorders, including Velocardiofacial (VCFS), DiGeorge (DGS) syndromes and combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic disease characterized by the accumulation of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 loss leads to these syndromes remain largely unclear. Here, we describe a mouse model of SLC25A1 deficiency that mimics human VCFS/DGS and D/L-2HGA.
View Article and Find Full Text PDFSci Data
December 2024
Department of Bio-Health Convergence, Kangwon National University, Chuncheon, 24341, Republic of Korea.
As molecular research on hemp (Cannabis sativa L.) continues to advance, there is a growing need for the accumulation of more diverse genome data and more accurate genome assemblies. In this study, we report the three-way assembly data of a cannabidiol (CBD)-rich cannabis variety, 'Pink Pepper' cultivar using sequencing technology: PacBio Single Molecule Real-Time (SMRT) technology, Illumina sequencing technology, and Oxford Nanopore Technology (ONT).
View Article and Find Full Text PDFMol Psychiatry
December 2024
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Psychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions.
View Article and Find Full Text PDFMetabolites
December 2024
Department of Radiation Convergence Engineering, College of Software and Digital Healthcare Convergence, Yonsei University, 1, Yeonsedae-gil, Heungeop-myeon, Wonju 26493, Republic of Korea.
Background/objectives: The acute stress response affects brain metabolites closely linked to the tricarboxylic acid (TCA) cycle. This response involves time-dependent changes in hormones and neurotransmitters, which contribute to resilience and the ability to adapt to acute stress while maintaining homeostasis. This physiological mechanism of metabolic dynamics, combined with time-series analysis, has prompted the development of new methods to observe the relationship between TCA cycle-related brain metabolites.
View Article and Find Full Text PDFCancer Res Treat
December 2024
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Purpose: This study aimed to conduct a comprehensive genetic analysis of patients with Langerhans cell histiocytosis (LCH), focusing on the frequency of MAPK pathway mutations, detailed mutation profiles of MAPK pathway genes, and their correlation with clinical features and prognosis in Korean LCH patients.
Materials And Methods: We performed targeted next-generation sequencing, capable of capturing exons from 382 cancer-related genes, on genomic DNA extracted from formaldehyde-fixed and paraffin-embedded samples of 45 pathologically confirmed LCH patients.
Results: The majority of patients (91.
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