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Single-cell landscape of alternative polyadenylation in human lymphoid hematopoiesis

Journal of molecular Cell Biology 2024年第7期16卷 30-45页

作者： Jiaqi Qiang Shan Yu Jun Li Yu Rong Xiaoshuang Wang Yong Zhu Fang Wang State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeĳing 100005China The Key Laboratory of RNA and Hematopoietic Regulation Chinese Academy of Medical SciencesBeĳing 100005China Eight-Year Medical Doctor Program Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeĳing 100730China Department of Endocrinology Key Laboratory of Endocrinology of National Health CommissionPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeĳing 100730China Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province Hangzhou 310030China Department of Cardiovascular Medicine Chongqing Emergency Medical CenterChongqing University Central HospitalChongqing 400014China College of Basic Medicine Chongqing Medical UniversityChongqing 400016China

Alternative polyadenylation(APA)is an essential post-transcriptional process that produces mature mRNA isoforms by regulating the usage of polyadenylation sites(PASs).APA is involved in lymphocyte activation;however,its role throughout the entire differentiation trajectory remains ***,we analyzed single-cell 3'-end transcriptome data from healthy subjects to construct a dynamic-APA landscape from hematopoietic stem and progenitor cells(HSPCs)to terminally differentiated *** analysis covered 19973 cells of 12 clusters from five lineages(B cells,CD4^(+)T cells,CD8^(+)T cells,natural killer cells,and plasmacytoid dendritic cells).A total of 2364 genes exhibited differential 3'-untranslated region(3'UTR)PAS usage,and 3021 genes displayed differential intronic cleavage during lymphoid *** observed a global trend of 3'UTR shortening during lymphoid ***,specific events of both 3'UTR shortening and lengthening were also identified within each *** APA patterns delineated three differentiation stages:HSPCs,precursor cells,and mature ***,we demonstrated that the conversion of naïve T cells to memory T cells was accompanied by dynamic APA in transcription factor-encoding genes(TCF7 and NFATC2IP),immune function-related genes(BCL2,CD5,CD28,GOLT1B,and TMEM59),and protein ubiquitination-related genes(UBE2G1,YPEL5,and SUMO3).These findings expand our understanding of the underlying molecular mechanisms of APA and facilitate studies on the regulatory role of APA in lymphoid hematopoiesis.

关键词： alternative polyadenylation hematopoiesis lymphoid differentiation post-transcription single-cell

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Safety,dosimetry,and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors:From preclinical testing to first-in-human study

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Acta Pharmaceutica Sinica B 2025年第2期15卷 707-721页

作者： Wei Guo Xuejun Wen Yuhang Chen Tianzhi Zhao Jia Liu Yucen Tao Hao Fu Hongjian Wang Weizhi Xu Yizhen Pang Liang Zhao Jingxiong Huang Pengfei Xu Zhide Guo Weibing Miao Jingjing Zhang Xiaoyuan Chen Haojun Chen Department of Nuclear Medicine and Minnan PET Center Xiamen Key Laboratory of Radiopharmaceuticalsthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China School of Clinical Medicine Fujian Medical UniversityFuzhou 350005China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics&Center for Molecular Imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen 361102China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 138667Singapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 138667Singapore Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 138667Singapore Department of Nuclear Medicine the First Affiliated HospitalFujian Medical UniversityFuzhou 350005China Department of Nuclear Medicine National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhou 350212China Fujian Key Laboratory of Precision Medicine for Cancer the First Affiliated HospitalFujian Medical UniversityFuzhou 350005China

Peptide receptor radionuclide therapy(PRRT)with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors(NETs).Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue(denoted as^(177)Lu-EB-TATE)is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic *** study aimed to enhance the in vivo stability,pharmacokinetics,and pharmacodynamics of^(177)Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain,resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical,^(177)Lu-LNC1010,for *** preclinical studies,^(177)Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor ***,we presented the first-in-human dose escalation study of^(177)Lu-LNC1010 in patients with advanced/metastatic NETs.^(177)Lu-LNC1010 was well-tolerated by all patients,with minor adverse effects,and exhibited significant uptake and prolonged retention in tumor lesions,with higher tumor radiation doses than those of^(177)*** PRRT efficacy results showed an 83%disease control rate and a 42%overall response rate after two^(177)Lu-LNC1010 treatment *** encouraging findings warrant further investigations through multicenter,prospective,and randomized controlled trials.

关键词： Radiolabeled somatostatin analog Neuroendocrine tumor Evans blue ^(177)Lu-LNC1010 Peptide receptor radionuclide therapy First-in-human dose escalation study

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Integrated proteomic profiling identifies amino acids selectively cytotoxic to pancreatic cancer cells

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The Innovation 2024年第3期5卷 138-145页

作者： Alfred Akinlalu Zachariah Flaten Komila Rasuleva Md Saimon Mia Aaron Bauer Santhalingam Elamurugan Nega Ejjigu Sudipa Maity Amara Arshad Min Wu Wenjie Xia Jia Fan Ang Guo Sijo Mathew Dali Sun Department of Electrical and Computer Engineering University of Denver2155 E Wesley AvenueDenverCO 80210USA Biomedical Engineering Program North Dakota State University1401 Centennial BoulevardEngineering AdministrationRoom 203FargoND 58102USA Department of Pharmaceutical Sciences School of PharmacyNorth Dakota State University1001 S.1401 Albrecht Boulevard Sudro HallFargoND 58102USA Materials and Nanotechnology Program North Dakota State University1410 North 14th AvenueCIE 201FargoND 58102USA Wenzhou Institute University of Chinese Academy of SciencesWenzhouZhejiang 325000China Department of Aerospace Engineering Iowa State UniversityAmesIA 50011USA Center for Cellular and Molecular Diagnostics Tulane University School of Medicine1430 Tulane AvenueNew OrleansLA 70112USA Department of Biochemistry and Molecular Biology Tulane University School of Medicine1430 Tulane AvenueNew OrleansLA 70112USA Knoebel Institute for Healthy Aging University of Denver2155 E Wesley AvenueDenverCO 80210USA

Pancreatic adenocarcinoma(PDAC)is one of the most deadly cancers,characterized by extremely limited therapeutic options and a poor prognosis,as it is often diagnosed during late disease *** and selective treatments are urgently needed,since current therapies have limited efficacy and significant side *** proteomics analysis of extracellular vesicles,we discovered an imbalanced distribution of amino acids secreted by PDAC tumor *** findings revealed that PDAC cells preferentially excrete proteins with certain preferential amino acids,including isoleucine and histidine,via extracellular *** amino acids are associated with disease progression and can be targeted to elicit selective toxicity to PDAC tumor *** in vitro and in vivo experiments demonstrated that supplementation with these specific amino acids effectively eradicated PDAC ***,we also identified XRN1 as a potential target for these amino *** high selectivity of this treatment method allows for specific targeting of tumor metabolism with very low toxicity to normal ***,we found this treatment approach is easy-to-administer and with sustained tumor-killing ***,our findings reveal that exocytosed amino acids may serve as therapeutic targets for designing treatments of intractable PDAC and potentially offer alternative treatments for other types of cancers.

关键词： finding identif selectivity

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Specificity of serological screening tests and reference laboratory tests to diagnose gambiense human African trypanosomiasis: a prospective clinical performance study

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Infectious Diseases of Poverty 2024年第4期13卷 48-63页

作者： Martial Kassi N'Djetchil Oumou Camara Mathurin Koffi Mamadou Camara Dramane Kaba Jacques Kabore Alkali Tall Brice Rotureau Lucy Glover Melika Barkissa Traorel Minayegninrin Kone Bamoro Coulibaly Guy Pacome Adingra Aissata Soumah Mohamed Gassama Abdoulaye Dansy Camara Charlie Franck Alfred Compaore Aissata Camara Salimatou Boiro Elena Perez Anton Paul Bessell Nick Van Reet Bruno Bucheton Vincent Jamonneau Jean-Mathieu Bart Philippe Solano Sylvain Bieler Veerle Lejon Laboratory of Biodiversity and Ecosystem Management Jean Lorougnon Guede UniversityDaloaCote d'ivoire National Program for Neglected Tropical Disease Control Patient ManagementMinistry of HealthConakryGuinea Trypanosomosis Research Unit Pierre Richet InstituteBouakeCote d'ivoire International Research and Development Centre on Livestock in Subhumid Zones Bobo-DioulassoBurkina Faso National Program for Malaria Control ConakryGuinea Parasitology Unit Institut Pasteur de GuineeConakryGuinea Trypanosome Molecular Biology Unit Department of Parasites and Insect VectorsPasteur InstituteParis Cite UniversityParisFrance Intertryp IRD-CIRAD-University of MontpellierMontpellierFrance Independent Consultant EdinburghUk Department of Biomedical Sciences Institute of Tropical MedicineAntwerpBelgium Foundation for Innovative New Diagnostics GenevaSwitzerland

Background Serological screening tests play a crucial role to diagnose gambiense human African trypanosomiasis (gHAT). Presently, they preselect individuals for microscopic confirmation, but in future "screen and treat" strategies they will identify individuals for treatment. Variability in reported specificities, the development of new rapid diagnostic tests (RDT) and the hypothesis that malaria infection may decrease RDT specificity led us to evaluate the specificity of 5 gHAT screening *** During active screening, venous blood samples from 1095 individuals from Cote d’Ivoire and Guinea were tested consecutively with commercial (CATT, HAT Sero-K-SeT, Abbott Bioline HAT 2.0) and prototype (DCN HAT RDT, HAT Sero-K-SeT 2.0) gHAT screening tests and with a malaria RDT. Individuals with ≥ 1 positive gHAT screening test underwent microscopy and further immunological (trypanolysis withT.b. gambiense LiTat 1.3, 1.5 and 1.6;indirect ELISA/T.b. gambiense;T.b. gambiense inhibition ELISA withT.b. gambiense LiTat 1.3 and 1.5 VSG) and molecular reference laboratory tests (PCR TBRN3, 18S and TgsGP;SHERLOCK 18S Tids, 7SLZoon, and TgsGP;Trypanozoon S2-RT-qPCR 18S2, 177T, GPI-PLC and TgsGP in multiplex;RT-qPCR DT8, DT9 and TgsGP in multiplex). Microscopic trypanosome detection confirmed gHAT, while other individuals were considered gHAT free. Differences in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by *** One gHAT case was diagnosed. Overall test specificities (n = 1094) were: CATT 98.9% (95%CI: 98.1–99.4%);HAT Sero-K-SeT 86.7% (95%CI: 84.5–88.5%);Bioline HAT 2.0 82.1% (95%CI: 79.7–84.2%);DCN HAT RDT 78.2% (95%CI: 75.7–80.6%);and HAT Sero-K-SeT 2.0 78.4% (95%CI: 75.9–80.8%). In malaria positives, gHAT screening tests appeared less specific, but the difference was significant only in Guinea for Abbott Bioline HAT 2.0 (P = 0.03) and HAT Sero-K-Set 2.0 (P = 0.0006). The specificitie

关键词： Human African trypanosomiasis Trypanosoma brucei gambiense Diagnosis Specificity Rapid diagnostic test Immunological test molecular test

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Dynamic Stromal Changes in Myelofibrosis Patients Pre/Post JAK Inhibition Is Revealed in Clinically Archived Bone Marrow Biopsies By Smooth Muscle Actin (SMA)-CD34 Dual Immunohistochemistry

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BLOOD 2021年 138卷 3286-3286页

作者： Wang, Katelyn Rashedi, Iran England, James T. Goswami, Rashmi S. Liontos, Larissa Peerani, Raheem Tierens, Anne Rauh, Michael J. Gupta, Vikas Tsui, Hubert Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Health Sciences Centre Toronto Canada Princess Margaret Cancer Centre University Health Network Toronto Canada Laboratory Medicine Program University Health Network Toronto Canada Department of Pathology and Molecular Medicine Queen's University Kingston Canada MPN Program The Princess Margaret Cancer Centre Toronto Canada Department of Laboratory Medicine and Molecular Diagnostics Sunnybrook Health Sciences Centre Markham Canada

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Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes

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eBioMedicine 2023年 90卷 104516-104516页

作者： Varun, Kumar Zoltan, Kender Alba, Sulaj Manuel, Blume Elisabeth, Kliemank Dimitrios, Tsilingiris Jan B, Groener Maik, Brune Khurrum, Shahzad Berend, Isermann Stephen, Herzig Thomas, Fleming Julia, Szendroedi Peter, Nawroth Stefan, Kopf Department of Endocrinology Diabetology and Clinical Chemistry (Internal Medicine I) University Hospital of Heidelberg Heidelberg Germany German Center for Diabetes Research (DZD) München-Neuherberg Germany European Molecular Biology Laboratory Advanced Light Microscopy Facility Heidelberg Germany Medicover Neuroendokrinologie Munich Germany Institute for Laboratory Medicine Clinical Chemistry and Molecular Diagnostics University Hospital of Leipzig Germany Helmholtz Diabetes Center Institute for Diabetes and Cancer Helmholtz Center Munich Germany Joint Heidelberg-IDC Translational Diabetes Program Internal Medicine I Heidelberg University Hospital Heidelberg Germany

Background: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes. Methods: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and ɤH2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-β1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years. Findings: db/db mice showed an increased nuclear ɤH2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression. Interpretation: In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis. Funding: This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Rese

关键词： Diabetic complications Diabetic kidney disease DNA-damage Fibrosis Restrictive lung disease Senescence Senescence-associated secretory phenotype Type 2 diabetes mellitus

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Novel POC Bionanosensor for Direct Detection of RNA-Virus Infections in Minutes

Novel POC Bionanosensor for Direct Detection of RNA-Virus In...

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作者： Maung, May Cui, Chengde Sinha, Saion Biomedical Engineering Program University of New Haven West HavenCT United States 12-15 Molecular Diagnostics BranfordCT United States

Viral infections (like different types of influenza virus) are becoming alarmingly common often leading to epidemics. Since Viruses can multiply from genomic materials it can spread the infection quickly as well as cause other complications like birth defects, autoimmune disease and even cancer. diagnostics of viral infection traditionally is performed using antigen-antibody reaction, which is time consuming and labor intensive. Also, viral infections can be latent or show false negative results when antibody reaction is tested. In-situ direct hybridization detection is possible by expensive, long and difficult radiation-based methods. Our group has developed a Carbon Nanotube (CNT) & Graphene based Bionanosensor (BNS) for rapid and direct detection of specific DNA sequences. In this technique, single-stranded (ss) DNA probe (known as priming) is immobilized on a substrate. This recognizes a specific complementary target DNA in a sample solution and gets hybridized leading to a detectable electrical signal. In this study we have expanded the scope of this BNS by using it to detect quick in-situ RNA hybridization. A sample of RNA was tested simultaneously in an array of 4 biosensors (each primed by the complementary sequence). The resistance across each of the biosensors was measured with a self-designed, feed-back controlled, balanced Wheatstone bridge circuit with an Arduino interface. A specific pattern related to hybridization was observed and a weighted average performed over 30 experiments. The sensors primed with the forward RNA was able to detect the complementary sequence in a mixed sample in 10 minutes from the starting time. © 2019 World Scientific Publishing Company.

关键词： Biosensors

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Assessment of Plasmodium antigens and CRP in dried blood spots with multiplex malaria array

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Journal of Parasitic Diseases 2021年第2期45卷 479-489页

作者： Jang, Ihn Kyung Aranda, Sara Barney, Rebecca Rashid, Andrew Helwany, Muhammad Rek, John C. Arinaitwe, Emmanuel Adrama, Harriet Murphy, Maxwell Imwong, Mallika Proux, Stephane Haohankhunnatham, Warat Ding, Xavier C. Nosten, François Greenhouse, Bryan Gamboa, Dionicia Domingo, Gonzalo J. Diagnostics Program PATH Seattle WA United States Infectious Diseases Research Collaboration Kampala Uganda Department of Medicine University of California at San Francisco San Francisco CA United States Faculty of Tropical Medicine Department of Molecular Tropical Medicine and Genetics Mahidol University Bangkok Thailand Faculty of Tropical Medicine Mahidol-Oxford Tropical Medicine Research Unit Shoklo Malaria Research Unit Mahidol University Mae Sot Thailand The Foundation for Innovative New Diagnostics Geneva Switzerland Nuffield Department of Medicine Centre for Tropical Medicine and Global Health University of Oxford Oxford United Kingdom Departamento de Ciencias Celulares y Moleculares Facultad de Ciencias y Filosofía Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia Lima Peru

Dried blood spots (DBS) typically prepared on filter papers are an ideal sample type for malaria surveillance by offering easy and cost-effective methods in terms of sample collection, storage, and transport. The objective of this study was to evaluate the applicability of DBS with a commercial multiplex malaria assay, developed to concurrently measure Plasmodium antigens, histidine-rich protein 2 (HRP2), Plasmodium lactate dehydrogenase (pLDH), and a host inflammatory biomarker, C-reactive protein (CRP), in whole blood. The assay conditions were optimized for DBS, and thermal stability for measurement of Plasmodium antigens and CRP in dried blood were determined. Performance of the multiplex assay on matched DBS and whole blood pellet samples was also evaluated using the clinical samples. The results indicate the acceptable performance in multiplex antigen detection using DBS samples. At cutoff levels for DBS, with a diagnostic specificity with a lower 95% confidence bound > 92%, diagnostic sensitivities against polymerase chain reaction (PCR)–confirmed malaria for HRP2, Pf LDH, Pv LDH, and Pan LDH were 93.5%, 80.4%, 21.3%, and 55.6%, respectively. The half-life of pLDH was significantly less than that of HRP2 in thermal stability studies. Results with DBS samples collected from Peru indicate that the uncontrolled storage conditions of DBS can result in inaccurate reporting for infection with P. falciparum parasites with hrp2/3 deletions. With careful consideration that minimizing the unfavorable DBS storage environment is essential for ensuring integrity of heat-labile Plasmodium antigens, DBS samples can be used as an alternative to liquid whole blood to detect P. falciparum with hrp2/3 deletions in malaria surveillance. © 2021, The Author(s).

关键词： Dried blood spot HRP2 Immunoassay LDH Malaria Multiplex

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Postoperative intravenous iron to treat iron-deficiency anaemia in patients undergoing cardiac surgery: a protocol for a pilot, multicentre, placebo-controlled randomized trial (the POAM trial)

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BJA Open 2024年 11卷 100303页

作者： Bartoszko, Justyna Miles, Sarah Ansari, Saba Grewal, Deep Li, Michelle Callum, Jeannie McCluskey, Stuart A. Lin, Yulia Karkouti, Keyvan Institute of Medical Science University of Toronto Department of Anesthesia and Pain Management Sinai Health System Women's College Hospital University Health Network Department of Anesthesiology and Pain Medicine University of Toronto Peter Munk Cardiac Centre University Health Network University of Toronto Quality in Utilization Education and Safety in Transfusion Research Program Department of Pathology and Molecular Medicine Kingston Health Sciences Centre and Queen's University Precision Diagnostics and Therapeutics Program Sunnybrook Health Sciences Centre Department of Laboratory Medicine and Pathobiology University of Toronto Institute for Health Policy Management and Evaluation University of Toronto Interdepartmental Division of Critical Care Department of Medicine University of Toronto Co-first author.

Background: Iron-deficiency anaemia, occurring in 30–40% of patients undergoing cardiac surgery, is an independent risk factor for adverse outcomes. Our long-term goal is to assess if postoperative i.v. iron therapy improves clinical outcomes in patients with preoperative iron-deficiency anaemia undergoing cardiac surgery. Before conducting a definitive RCT, we first propose a multicentre pilot trial to establish the feasibility of the definitive trial. Methods: This internal pilot, double-blinded, RCT will include three centres. Sixty adults with preoperative iron-deficiency anaemia undergoing non-emergency cardiac surgery will be randomised on postoperative day 2 or 3 to receive either blinded i.v. iron (1000 mg ferric derisomaltose) or placebo. Six weeks after surgery, patients who remain iron deficient will receive a second blinded dose of i.v. iron according to their assigned treatment arm. Patients will be followed for 12 months. Clinical practice will not be otherwise modified. For the pilot study, feasibility will be assessed through rates of enrolment, protocol deviations, and loss to follow up. For the definitive study, the primary outcome will be the number of days alive and out of hospital at 90 days after surgery. Ethics and dissemination: The trial has been approved by the University Health Network Research Ethics Board (REB # 22-5685;approved by Clinical Trials Ontario funding on 22 December 2023) and will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practices guidelines, and regulatory requirements. Clinical trial registration: NCT06287619. © 2024 The Authors

关键词： anaemia infusions intravenous iron compounds iron deficiency perioperative care

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Continuing education and professional development: Unifying opportunities for genetic counselors globally

Genetics in Medicine Open

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Genetics in Medicine Open 2024年第Suppl 2期2卷 101854-101854页

作者： Valverde, Kathleen D. Hartman, Tiffiney R. Reichert, Sara L. Bennett, Robin L. Dudek, Martha Duquette, Debra Riconda, Daniel Cox, Nancy J. Jarvik, Gail P. Elsea, Sarah H. McNally, Elizabeth M. Worley, Kim C. Rader, Daniel J. Master of Science in Genetic Counseling Program Department of Genetics Perelman School of Medicine University of Pennsylvania Philadelphia PA United States Department of Pathology Division of Genomic Diagnostics The Children's Hospital of Philadelphia Philadelphia PA United States Division of Medical Genetics Department of Medicine University of Washington Seattle WA United States Master of Genetic Counseling Program Vanderbilt University School of Medicine Department of Obstetrics and Gynecology Division of Maternal-Fetal Medicine Vanderbilt University Medical Center Nashville TN United States Feinberg School of Medicine Chicago IL United States Department of Molecular and Human Genetics and the School of Health Professions Baylor College of Medicine Houston TX United States Division of Genetic Medicine Vanderbilt University Nashville TN United States Department of Molecular and Human Genetics Baylor College of Medicine Houston TX United States Center for Genetic Medicine Northwestern University Chicago IL United States Departments of Genetics Medicine and Pediatrics Perelman School of Medicine at the University of Pennsylvania Philadelphia PA United States

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