2,448 results match your criteria: "Institute for Human Genetics[Affiliation]"

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

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In spring 2022, the inaugural cohort of Genetic and Genomic Counseling MSc students graduated from the Medical University of Innsbruck, representing a significant milestone for the establishment of the genetic counselor (GC) profession in the German-speaking countries. A pivotal component of their education was a 15-week clinical training period. The placement experiences of both students and supervisors offered valuable insights into the attitudes of medical geneticists toward the profession.

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Corrigendum: Longitudinal associations between microRNAs and weight in the diabetes prevention program.

Front Endocrinol (Lausanne)

December 2024

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States.

[This corrects the article DOI: 10.3389/fendo.2024.

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CNVizard-a lightweight streamlit application for an interactive analysis of copy number variants.

BMC Bioinformatics

December 2024

Medical Faculty, Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, North-Rhine-Westphalia, Germany.

Background: Methods to call, analyze and visualize copy number variations (CNVs) from massive parallel sequencing data have been widely adopted in clinical practice and genetic research. To enable a streamlined analysis of CNV data, comprehensive annotations and good visualizations are indispensable. The ability to detect single exon CNVs is another important feature for genetic testing.

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Palovarotene (Sohonos), a synthetic retinoid for reducing new heterotopic ossification in fibrodysplasia ossificans progressiva: history, present, and future.

JBMR Plus

January 2025

Translational Research Program in Pediatric Orthopedics, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.

Retinoids are metabolic derivatives of vitamin A and play crucial roles in the regulation of various tissues and organs during prenatal and postnatal development. Active retinoids, like all-trans-retinoic acid, are synthesized in the cytoplasm and subsequently interact with nuclear retinoic acid receptors (RARα, RARβ, and RARγ) to enhance transcription of specific genes. In the absence of retinoids, RARs can still bind to response elements of target genes but repress their transcription.

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To assess the suitability of genome sequencing (GS) as the second step in the diagnostics of patients with the features of 11p15.5-associated imprinting disorders (ImpDis: Silver-Russell syndrome [SRS], Beckwith-Wiedemann syndrome [BWS]), we performed short-read GS in patients negatively tested for imprinting disturbances. Obtaining a genetic diagnosis for patients with the features of these syndromes is challenging due to the clinical and molecular heterogeneity and overlap, and many patients remain undiagnosed after the currently suggested stepwise diagnostic workup.

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The ability of cells to maintain distinct identities and respond to transient environmental signals requires tightly controlled regulation of gene networks. These dynamic regulatory circuits that respond to extracellular cues in primary human cells remain poorly defined. The need for context-dependent regulation is prominent in T cells, where distinct lineages must respond to diverse signals to mount effective immune responses and maintain homeostasis.

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Label-free single-cell RNA multiplexing leveraging genetic variability.

Nat Commun

December 2024

Department of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), Medical Faculty, RWTH Aachen University, Aachen, Germany.

Single cell RNA sequencing has provided unprecedented insights into the molecular cues and cellular heterogeneity underlying human disease. However, the high costs and complexity of single cell methods remain a major obstacle for generating large-scale human cohorts. Here, we compare current state-of-the-art single cell multiplexing technologies, and provide a widely applicable demultiplexing method, SoupLadle, that enables simple, yet robust high-throughput multiplexing leveraging genetic variability of patients.

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Characterizing the genetic architecture of drug response using gene-context interaction methods.

Cell Genom

December 2024

Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Identifying factors that affect treatment response is a central objective of clinical research, yet the role of common genetic variation remains largely unknown. Here, we develop a framework to study the genetic architecture of response to commonly prescribed drugs in large biobanks. We quantify treatment response heritability for statins, metformin, warfarin, and methotrexate in the UK Biobank.

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Background: The identification of a heterozygous exonic GGC repeat expansion in ZFHX3 underlying spinocerebellar ataxia type 4 (SCA4) has solved a 25-year diagnostic conundrum. We used adaptive long-read sequencing to decipher the pathogenic expansion in the index Utah family and an unrelated family from Iowa of Swedish ancestry. Contemporaneous to our discovery, other groups identified the same repeat expansion in affected individuals from Utah, Sweden, and Germany, highlighting the current pivotal time for detection of novel repeat expansion disorders.

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Over the past decade, single-cell genomics technologies have allowed scalable profiling of cell-type-specific features, which has substantially increased our ability to study cellular diversity and transcriptional programs in heterogeneous tissues. Yet our understanding of mechanisms of gene regulation or the rules that govern interactions between cell types is still limited. The advent of new computational pipelines and technologies, such as single-cell epigenomics and spatially resolved transcriptomics, has created opportunities to explore two new axes of biological variation: cell-intrinsic regulation of cell states and expression programs and interactions between cells.

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Mapping genes for human face shape: Exploration of univariate phenotyping strategies.

PLoS Comput Biol

December 2024

Department of Electrical Engineering, ESAT/PSI, KU Leuven, Leuven, Belgium.

Human facial shape, while strongly heritable, involves both genetic and structural complexity, necessitating precise phenotyping for accurate assessment. Common phenotyping strategies include simplifying 3D facial features into univariate traits such as anthropometric measurements (e.g.

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Inferring human phenotypes using ancient DNA: from molecules to populations.

Curr Opin Genet Dev

November 2024

Bakar Computational Health Science Institute, University of California San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA. Electronic address:

Article Synopsis
  • The study reviews how ancient DNA (aDNA) has improved our understanding of human migrations but has limitations in linking genetic information to observable traits (phenotypes).
  • It discusses recent advancements in predicting ancient phenotypes using machine learning techniques and emphasizes the challenges posed by the complex genetic traits found in various human populations.
  • The authors suggest a new method that combines predictions of molecular traits, which are more stable over time, with non-genetic factors to enhance the understanding of ancient individuals' characteristics.
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Congenital heart defects (CHD) arise in part due to inherited genetic variants that alter genes and noncoding regulatory elements in the human genome. These variants are thought to act during fetal development to influence the formation of different heart structures. However, identifying the genes, pathways, and cell types that mediate these effects has been challenging due to the immense diversity of cell types involved in heart development as well as the superimposed complexities of interpreting noncoding sequences.

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The domestication of wild canids led to dogs no longer living in the wild but instead residing alongside humans. Extreme changes in behavior and diet associated with domestication may have led to the relaxation of the selective pressure on traits that may be less important in the domesticated context. Thus, here we hypothesize that strongly deleterious mutations may have become less deleterious in domesticated populations.

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Context: Roux-en-Y gastric bypass (RYGB) has deleterious effects on bone mass, microarchitecture, and strength. The skeletal effects of sleeve gastrectomy (SG), now the most commonly performed bariatric surgical procedure, are incompletely understood.

Objective: We examined changes in bone turnover, areal and volumetric bone mineral density (aBMD, vBMD), and appendicular bone microarchitecture and estimated strength after SG.

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Article Synopsis
  • * It used family-based statistical analysis methods to find that there is a significant genetic component influencing both LBP_DS and the measured body composition aspects and adipokines.
  • * The results suggest that different genetic factors impact LBP_DS, showing a complex relationship where adipokine variations and body composition measurements may independently affect back pain disability without overlapping genetic influences.
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Addressing Cross-Specialty Clinical Genetics Education Needs.

J Contin Educ Health Prof

November 2024

Dr. Lindquist: Assistant Professor and Specialist, Departments of Epidemiology and Biostatistics, Obstetrics, Gynecology, and Reproductive Sciences, and the Institute for Human Genetics at the University of California, San Francisco, San Francisco, CA.

Introduction: Advances in genomics are transforming clinical practice, but there are too few genetics professionals to meet increasing demand. Moreover, many nongeneticist clinicians feel unprepared to incorporate genetics into practice. This study assessed clinicians' unmet genomics educational needs at a single academic institution.

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While context-type-specific regulation of genes is largely determined by cis-regulatory regions, attempts to identify cell type-specific eQTLs are complicated by the nested nature of cell types. We present hierarchical eQTL (H-eQTL), a network-based model for hierarchical annotation of bulk-derived eQTLs to levels of a cell type tree using single-cell chromatin accessibility data and no clustering of cells into discrete cell types. Using our model, we annotate bulk-derived eQTLs from the developing brain with high specificity to levels of a cell type hierarchy, which allows sensitive detection of genes with multiple distinct non-coding elements regulating their expression in different cell types.

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Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder characterized by neonatal hypotonia, followed by hyperphagia and obesity. Most PWS cases exhibit megabase-scale deletions of paternally imprinted 15q11-q13 locus. However, several PWS patients have been identified harboring much smaller deletions encompassing the SNORD116 gene cluster, suggesting these genes are direct drivers of PWS phenotypes.

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With advances in cancer screening and treatment, there is a growing population of cancer survivors who may develop subsequent primary cancers. While hereditary cancer syndromes account for only a portion of multiple cancer cases, we sought to explore the role of common genetic variation in susceptibility to multiple primary tumors. We conducted a cross-ancestry genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) of 10,983 individuals with multiple primary cancers, 84,475 individuals with single cancer, and 420,944 cancer-free controls from two large-scale studies.

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Three-dimensional genome organization plays a critical role in gene regulation, and disruptions can lead to developmental disorders by altering the contact between genes and their distal regulatory elements. Structural variants (SVs) can disturb local genome organization, such as the merging of topologically associating domains upon boundary deletion. Testing large numbers of SVs experimentally for their effects on chromatin structure and gene expression is time and cost prohibitive.

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Disordered electron transfer: New forms of defective steroidogenesis and mitochondriopathy.

J Clin Endocrinol Metab

November 2024

Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland.

Article Synopsis
  • * Most steroidogenic enzymes are cytochrome P450s, requiring electron donation from specific proteins (POR or FDXR/FDX), with deficiencies in these proteins linked to various health issues, including the rare CAH caused by POR deficiency.
  • * Recent research has found mutations in FDXR linked to serious neurological symptoms and adrenal insufficiency, indicating the need for interdisciplinary collaboration among specialists when evaluating these patients.
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Psoriasis is an immune-mediated skin disease known to be associated with a higher risk of cardiometabolic comorbidities such as hypertension, myocardial infarction, and stroke. GLP-1 receptor agonists (GLP-1RAs) are medications approved to treat type 2 diabetes mellitus and obesity and have been reported to improve psoriasis. As more psoriasis patients start GLP-1RAs for approved indications, it is of interest to understand the impact of GLP-1RAs on both psoriasis and associated cardiovascular risk.

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