Research Topics
Genomes and Genes
| Alan H BeggsSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
MTM1 mutation associated with X-linked myotubular myopathy in Labrador RetrieversAlan H Beggs
Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research at Children s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 107:14697-702. 2010..These data demonstrate that XLMTM in Labrador Retrievers is a faithful genetic model of the human condition...- Selenoprotein N deficiency in mice is associated with abnormal lung developmentBehzad Moghadaszadeh
3Division of Genetics, Boston Children s Hospital, 300 Longwood Ave, CLSB 15026, Boston, MA 02115, USA
FASEB J 27:1585-99. 2013..Moghadaszadeh, B., Rider B. E., Lawlor, M. W., Childers, M. K., Grange, R. W., Gupta, K., Boukedes, S. S., Owen, C. A., Beggs, A. H. Selenoprotein N deficiency in mice is associated with abnormal lung development... - Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathyMichael W Lawlor
Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, CLSB 15026, Boston, MA 02115, USA
Skelet Muscle 1:23. 2011..abstract:.. 
Gene expression profiling of Duchenne muscular dystrophy skeletal muscleJudith N Haslett
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
Neurogenetics 4:163-71. 2003..It also highlights a large number of unknown genes whose expression is altered and whose identity therefore becomes important in understanding the pathogenesis of muscular dystrophy...- Variations in gene expression among different types of human skeletal musclePeter B Kang
Genomics Program, Enders 561, Howard Hughes Medical Institute and Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Muscle Nerve 32:483-91. 2005..This approach may be extended to a broader survey, potentially elucidating a molecular classification of the skeletal muscles... - A splice site mutation in laminin-α2 results in a severe muscular dystrophy and growth abnormalities in zebrafishVandana A Gupta
Genomics Program and Division of Genetics, Boston Children s Hospital, Harvard Medical School, The Manton Center for Orphan Disease Research, Boston, Massachusetts, United States of America
PLoS ONE 7:e43794. 2012..This laminin-α2 deficient mutant fish represents a novel disease model to develop therapies for modulating splicing defects in congenital muscular dystrophies and to restore the muscle function in human patients with CMD... - Serotonin-related FEV gene variant in the sudden infant death syndrome is a common polymorphism in the African-American populationKevin G Broadbelt
Department of Pathology, Enders Building Room 1111, Children s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
Pediatr Res 66:631-5. 2009..128-(191_192)dupA). The polymorphism seems to be a common, likely nonpathogenic, variant in the African-American population... - Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemiaHanna T Gazda
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
Stem Cells 24:2034-44. 2006..Downregulation of c-myb expression, which causes complete failure of fetal liver erythropoiesis in knockout mice, suggests a link between RPS19 mutations and reduced erythropoiesis in DBA... - Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscleDespina Sanoudou
Division of Genetics, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 100:4666-71. 2003..This comprehensive study of downstream molecular consequences of NM gene mutations provides insights in the cellular events leading to the NM phenotype... - Reproducibility of gene expression across generations of Affymetrix microarraysAshish Nimgaonkar
Informatics Program, Children s Hospital, Harvard Medical School, Boston, MA, USA
BMC Bioinformatics 4:27. 2003..In this study the reproducibility of gene expression levels across two generations of Affymetrix GeneChips (HuGeneFL and HG-U95A) was measured... - Expression profiling and identification of novel genes involved in myogenic differentiationKinga K Tomczak
Genetics Division, Children's Hospital, Boston, Massachusetts 02115, USA
FASEB J 18:403-5. 2004.... - Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemiaHanna T Gazda
Division of Genetics, Children s Hospital Boston, Boston, MA 02115, USA
Am J Hum Genet 79:1110-8. 2006..This finding strongly suggests that DBA is a disorder of ribosome synthesis and that mutations in other RP or associated genes that lead to disrupted ribosomal biogenesis and/or function may also cause DBA... - α-Actinin-2 deficiency results in sarcomeric defects in zebrafish that cannot be rescued by α-actinin-3 revealing functional differences between sarcomeric isoformsVandana Gupta
Division of Genetics, Children s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
FASEB J 26:1892-908. 2012..These data provide functional evidence that the primary sequences of α-actinin-2 and α-actinin-3 evolved differences to optimize their functions... - Transcriptional profile of postmortem skeletal muscleDespina Sanoudou
Genetics Division and Genomics Program, Boston, Massachusetts 02115, USA
Physiol Genomics 16:222-8. 2004..Knowledge of these changes is important for proper interpretation of gene expression studies utilizing autopsy specimens... - Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathyMichael W Lawlor
Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Boston Children s Hospital, Harvard Medical School, Boston, MA, USA
Hum Mol Genet 22:1525-38. 2013..These promising findings suggest that even low levels of myotubularin protein replacement can improve the muscle weakness and reverse the pathology that characterizes XLMTM... - Myotubularin-deficient myoblasts display increased apoptosis, delayed proliferation, and poor cell engraftmentMichael W Lawlor
Division of Genetics and the Program in Genomics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
Am J Pathol 181:961-8. 2012.... - Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2Pankaj B Agrawal
Genomics Program, the Divisions of Genetics and Neonatology, Children s Hospital Boston, Boston, MA, 02115, USA
Am J Hum Genet 80:162-7. 2007.... - Skeletal muscle repair in a mouse model of nemaline myopathyDespina Sanoudou
Program in Genomics and Genetics Division, Children's Hospital Boston, Harvard Medical School, MA 02115, USA
Hum Mol Genet 15:2603-12. 2006..Evidence suggesting elevated focal repair was observed in nemaline muscle in electron micrographs. This analysis reveals that NM is characterized by a novel repair feature operating in multiple different muscles... - Fast-twitch sarcomeric and glycolytic enzyme protein loss in inclusion body myositisKenneth C Parker
Harvard Partners Center for Genetics and Genomics, Proteomics Core, Harvard Medical School, Boston, Massachusetts USA
Muscle Nerve 39:739-53. 2009..Although muscle atrophy has long been recognized in IBM, these studies are the first to report specific proteins which are reduced in quantity in IBM muscle... - Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutationsPankaj B Agrawal
Genomics Program and Division of Genetics, Children s Hospital Boston, MA 02115, USA
Ann Neurol 56:86-96. 2004..Overall, ACTA1 mutations are a common cause of NM, accounting for more than half of severe cases and 26% of all NM cases in this series... - Automated DNA mutation detection using universal conditions direct sequencing: application to ten muscular dystrophy genesRichard R Bennett
Program in Genomics and Division of Genetics, and The Manton Center for Orphan Disease Research, Children s Hospital Boston, Boston, Massachusetts, USA
BMC Genet 10:66. 2009..If true, this would allow automation and optimization of the mutation detection process resulting in reduced cost and increased throughput... - Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositisRonan J Walsh
Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Arthritis Rheum 56:3784-92. 2007.... - Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathyChristopher R Pierson
Department of Pathology, Division of Neuropathology, Children s Hospital Boston and Brigham, 300 Longwood Avenue, Boston, MA 02115, USA
Neuromuscul Disord 17:562-8. 2007..Failure to attain and/or maintain myofiber size, along with fiber type perturbations and the misplacement of myofiber nuclei and other organelles, are important components of XLMTM muscle pathology... - Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemiaHanna T Gazda
Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, 3 BlackfanCircle, Boston, MA 02115, USA
Hum Mutat 33:1037-44. 2012..We also found a deletion in RPL19 and missense mutations in RPL3 and RPL23A, which may be variants of unknown significance. Together with RPL5, RPL11, and RPS7, RPL26 is the fourth RP regulating p53 activity that is linked to DBA... - Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicoresSteven E Boyden
Division of Genetics, Program in Genomics, and The Manton Center for Orphan Disease Research, Children s Hospital Boston, Boston, MA 02115, USA
Neurogenetics 13:115-24. 2012..Our data establish the importance of MEGF10 in human skeletal muscle and suggest satellite cell dysfunction as a novel myopathic mechanism... - Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patientsHanna T Gazda
Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, Boston, MA 02115, USA
Am J Hum Genet 83:769-80. 2008.... - Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportionMichael W Lawlor
Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
Hum Mutat 31:176-83. 2010..Several mutation-negative cases exhibited other abnormalities, such as central nuclei and central cores. These results support the utility of the CFTD diagnosis in directing the course of genetic testing... - Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmiaIgor Splawski
Department of Cardiology, Children s Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA
Science 297:1333-6. 2002..However, Y1102 may be a useful molecular marker for the prediction of arrhythmia susceptibility in the context of additional acquired risk factors such as the use of certain medications... - Ddx18 is essential for cell-cycle progression in zebrafish hematopoietic cells and is mutated in human AMLElspeth M Payne
Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Blood 118:903-15. 2011.... - Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenancePankaj B Agrawal
Genomics Program and Division of Genetics, The Manton Center for Orphan Disease Research, Boston, MA 02115, USA
Hum Mol Genet 21:2341-56. 2012..Overall, cofilin-2, although not critical for muscle development, is essential for muscle maintenance... - Melanoma cell adhesion molecule is a novel marker for human fetal myogenic cells and affects myoblast fusionMassimiliano Cerletti
Division of Genetics and Program in Genomics, Children s Hospital Boston, 320 Longwood Avenue, Boston, MA 02115, USA
J Cell Sci 119:3117-27. 2006..These studies identify M-CAM as a novel marker for myogenic progenitors in human fetal muscle and confirm that downregulation of this protein promotes myoblast fusion... - Distinctive patterns of microRNA expression in primary muscular disordersIris Eisenberg
Howard Hughes Medical Institute, Program in Genomics, Division of Genetics, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 104:17016-21. 2007.... - X-linked myotubular and centronuclear myopathiesChristopher R Pierson
Department of Pathology, Children s Hospital Boston, Massachusetts 02115, USA
J Neuropathol Exp Neurol 64:555-64. 2005..Currently the responsible gene(s) remain unknown. This review will explore the historical evolution in understanding of these myopathies and give an update on their histopathologic features, genetics and pathogenesis... - Dynamic regulation of endothelial NOS mediated by competitive interaction with alpha-actinin-4 and calmodulinYukio Hiroi
Vascular Medicine Research, Brigham and Women s Hospital, 65 Landsdowne Street, Boston, MA 02139, USA
FASEB J 22:1450-7. 2008..These findings indicate that eNOS activity in vascular endothelial cells is tonically and dynamically regulated by competitive interaction with alpha-actinin-4 and calmodulin... - The zebrafish dag1 mutant: a novel genetic model for dystroglycanopathiesVandana Gupta
Genomics Program and Division of Genetics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, Boston, MA 02115, USA
Hum Mol Genet 20:1712-25. 2011.... - Severe arrhythmia disorder caused by cardiac L-type calcium channel mutationsIgor Splawski
Howard Hughes Medical Institute, Department of Cardiology, and Genomics Program and Division of Genetics, Children s Hospital, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 102:8089-96; discussion 8086-8. 2005..These data indicate that gain-of-function mutations of CaV1.2 exons 8 and 8A cause distinct forms of TS... - Selenoproteins and their impact on human health through diverse physiological pathwaysBehzad Moghadaszadeh
Children's Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
Physiology (Bethesda) 21:307-15. 2006.... - The influence of muscle type and dystrophin deficiency on murine expression profilesJudith N Haslett
Division of Genetics and Genomics Program, Children s Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA
Mamm Genome 16:739-48. 2005..Further exploration of the genes that most distinguish these muscles may help explain the origins of the biomechanical differences and the reasons why some muscles are more resistant than others to dystrophin deficiency... - Evidence by molecular profiling for a placental origin of infantile hemangiomaCarmen M Barnes
Vascular Biology Program and Department of Surgery, Children s Hospital and Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 102:19097-102. 2005..Furthermore, it suggests that the unique self-limited growth of infantile hemangioma may, in fact, mirror the lifetime of placental endothelium... - RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutationsHanna T Gazda
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Br J Haematol 127:105-13. 2004..Our data support the notion that, in addition to rare DBA patients with the deletion of one allele, the disease in certain other RPS19 mutant patients is because of RPS19 protein haplo-insufficiency... - Multiple serotonergic brainstem abnormalities in sudden infant death syndromeDavid S Paterson
Department of Pathology, Children s Hospital Boston and Harvard Medical School, Boston, MA, USA
JAMA 296:2124-32. 2006..Previously, abnormalities in 5-HT receptor binding in the medullae of infants dying from sudden infant death syndrome (SIDS) were identified, suggesting that medullary 5-HT dysfunction may be responsible for a subset of SIDS cases... - Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscleJudith N Haslett
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 99:15000-5. 2002.... - Inhibition of activin receptor type IIB increases strength and lifespan in myotubularin-deficient miceMichael W Lawlor
Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
Am J Pathol 178:784-93. 2011..These results support ActRIIB-mFC as an effective treatment for the weakness observed in myotubularin deficiency... - Genotype-phenotype correlations in nemaline myopathy caused by mutations in the genes for nebulin and skeletal muscle alpha-actinCarina Wallgren-Pettersson
Department of Medical Genetics, University of Helsinki, Helsinki, Finland
Neuromuscul Disord 14:461-70. 2004..Finding the causative mutation(s) determines the mode of inheritance and permits prenatal diagnosis if requested, but will not as such permit prognostication... - Molecular classification of nemaline myopathies: "nontyping" specimens exhibit unique patterns of gene expressionDespina Sanoudou
Genomics Program and Divisison of Genetics, Children's Hospital Boston, and Harvard Medical School, MA 20115, USA
Neurobiol Dis 15:590-600. 2004..Determination of the specific molecular differences in NM subgroups may eventually lead to improved prognostic determinations and treatment of these patients... - Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemiaJason E Farrar
Division of Pediatric Oncology, Department of Oncology, Kimmel Comprehensive Cancer Center
Blood 112:1582-92. 2008..The results also establish that haploinsufficiency of large ribosomal subunit proteins contributes to bone marrow failure and potentially cancer predisposition... - Mutations in dynamin 2 cause dominant centronuclear myopathyMarc Bitoun
INSERM U582, Institute of Myology, IFR14, Groupe Hospitalier Pitie Salpetriere, UPMC, 47 Boulevard de l Hopital, 75651 Paris Cedex 13, France
Nat Genet 37:1207-9. 2005..The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function... - Rod distribution and muscle fiber type modification in the progression of nemaline myopathyJuliana Gurgel-Giannetti
Centro de Estudos do Genoma Humano, Department of Biology, IB, School of Medicine, , SP-CEP, Brazil
J Child Neurol 18:235-40. 2003.... - Muscle disease caused by mutations in the skeletal muscle alpha-actin gene (ACTA1)John C Sparrow
Department of Biology, University of York, York, YO10 5DD, UK
Neuromuscul Disord 13:519-31. 2003..g. actin myopathy. This would suggest that interference with certain actin functions may be more associated with certain phenotypes, though the exact pathophysiology of the actin mutations remains unknown... - Deficiency of muscle alpha-actinin-3 is compatible with high muscle performanceEdmar Zanoteli
Department of Neurology, , , Brazil
J Mol Neurosci 20:39-42. 2003..The deficiency of ACTN3 in the muscle tissue of endurance athletes confirmed the redundancy of this protein for muscle function, even in muscles that are highly required... - Telethonin protein expression in neuromuscular disordersMariz Vainzof
Center for the Study of the Human Genome, Department Biology, IBUSP, University of Sao Paulo, R do Matão, 277, sala 220 Cidade Universitária, Sao Paulo, Brazil
Biochim Biophys Acta 1588:33-40. 2002..Therefore, the primary deficiency of calpain-3, dysferlin, sarcoglycans, and dystrophin do not seem to alter telethonin expression... - AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasisAnna Buj-Bello
Department of Neurobiology and Genetics, INSERM U596, CNRS UMR 7104, Universite Louis Pasteur de Strasbourg, College de France, 67404 Illkirch, France
Hum Mol Genet 17:2132-43. 2008..This study provides a proof-of-principle that local delivery of an AAV vector expressing myotubularin can improve the motor capacities of XLMTM muscle and represents a novel approach to study myotubularin function in skeletal muscle...
Research Grants
- Alpha-actinins in normal and diseased muscleAlan Beggs; Fiscal Year: 2007..Our results may also lead to insights into the role(s) that alpha-actinin genotypes may play in modulating and/or causing human neuromuscular disease. ..
- SARCOMERIC PROTEINS IN NORMAL AND DISEASED MUSCLEAlan Beggs; Fiscal Year: 2005..Success in this project will enable accurate diagnostic and prognostic testing for all NM patients as well as shed new light on the structure and functions of normal and abnormal Z lines and thin filaments in skeletal muscle. ..
- ALPHA ACTININS IN NORMAL AND DISEASED MUSCLEAlan Beggs; Fiscal Year: 2000..These experiments will also increase our understanding of alpha-actinin function and identify new interactions with existing and novel muscle proteins at the Z-line and elsewhere. ..
- Alpha-actinins in normal and diseased muscleAlan H Beggs; Fiscal Year: 2010..Our results may also lead to insights into the role(s) that alpha-actinin genotypes may play in modulating and/or causing human neuromuscular disease. ..