Information for Researchers

LIke ThisLIke ThisLIke ThisLIke ThisLIke This

Research Overview

The fundamental goals of the Beggs Laboratory are to understand the molecular biology of skeletal muscle and to use this information to study inherited disorders of muscle function. To achieve this, our laboratory is taking four complementary approaches.

The first approach is to identify and characterize new muscle-specific genes and proteins and learn as much as possible about their basic biology. The underlying assumption is that these new genes are likely to include ones that are defective in patients with various congenital myopathies. Much previous work has concentrated on the α-actinins which are essential Z-line proteins. Current studies include several new sarcomeric proteins identified through interactions with α-actinin.

show_more_start

After learning about the cell biology and biochemistry of normal genes and proteins, we are then in a position to look for abnormalities of these genes in patients with muscle weakness. Thus, the second approach is to ascertain and enroll patients and families with various congenital myopathies and then study their DNA and muscle to find and understand the causes of their disorders. In the past few years, we have made much progress in understanding the basis of nemaline myopathy, including the identification of three thin filament proteins involved in this disorder. Current studies are also focusing on myotubular/centronucluclear myopathy, multi/minicore myopathies and other forms of congenital myopathy, including undefined cases without firm diagnoses. Knowing the genetic basis for each disorder will be critical to designing specific and effective treatments for some of these diseases.

The third approach is to learn as much as possible about the physiologic state of diseased muscle from patients with congenital myopathy. One frustrating aspect of medical genetics today is that knowing the exact genetic defect has often not allowed us to fully understand how the disease is caused and, more importantly, how we can treat it. Utilizing microarray technology, we are studying global gene expression patterns to determine the "downstream" or secondary consequences of particular genetic mutations and to identify novel muscle genes for further study. These genomic and proteomic approaches are yielding important new insights into basic muscle biology as well as the pathophysiology of inherited muscle diseases.

The fourth approach is to employ cellular and animal models of the congenital myopathies in order to better understand the disease process. In order to find a cure for a genetic disease, it is crucial to study the function of the normal gene to understand how its deficiency can cause the disease. Cellular and animal models have been proven to be indispensable tools for this purpose. In the case of muscular disease, C2C12 cells which are derived from a muscle cell line are an excellent choice since they can form myotubes (muscle cells) in vitro. These myotubes can twitch (contract) and to some extent mimic the muscle function. Furthermore, we now have the technology to easily inactivate ("turn off") a specific gene of interest in these cells in order to study the consequences of its deficiency. Using a mouse model of x-linked myotubular myopathy, we are learning more about various treatment options.

show_more_end


Publications

Below is a partial listing of laboratory publications (with links to .pdf files) categorized by subject area. Please select from the following categories:

Cloning and characterization of genes for sarcomeric Z line proteins

show_more_start

  1. Beggs AH, Byers TJ, Knoll JHM, Boyce FM, Bruns GAP, Kunkel LM. Cloning and characterization of two human skeletal muscle α-actinin genes located on chromosomes one and eleven. J Biol Chem 1992; 267:9281-9288.
  2. Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M. Competitive binding of α-actinin and calmodulin to the NMDA receptor. Nature, 1997; 385:439-442.
  3. Wyszynski M, Kharazia V, Shanghvi R, Rao A, Beggs AH, Craig AM, Weinberg R, Sheng M. Differential regional expression and ultrastructural localization of α-actinin-2, a putative NMDA receptor anchoring protein, in rat brain. J Neurosci, 1998;18:1383-1392.
  4. Chan Y-m, Tong H-Q, Beggs AH, Kunkel LM. Human skeletal muscle-specific α-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo. Biochem Biophys Res Comm, 1998; 248:134-139.
  5. Hance JE, Fu SY, Watkins SC, Beggs AH, Michalak M. α2-actinin is a new component of the dystrophin glycoprotein complex. Arch Biochem Biophys, 1999; 365:216-222.
  6. Takada F, Vander Woude DL, Tong H-Q, Thompson TG, Watkins SC, Kunkel LM, Beggs AH. Myozenin: An α-actinin and γ-filamin-binding protein of skeletal muscle Z lines. Proc Natl Acad Sci USA 2001; 98:1595-1600.
  7. Mills M, Yang N, Weinberger R, Vander Woude DL, Beggs AH, Easteal S, North K. Differential expression of the actin binding proteins, α-actinin-2 and -3 in different species: implications for the evolution of functional redundancy. Hum Molec Genet, 2001; 10:1335-1346.
  8. Takada F, Beggs AH. α-Actinins. In: Encyclopedia of Molecular Medicine. Creighton TE ed. J Wiley & Sons, Inc., New York 2002; 122-127.

show_more_end

Basic biology of skeletal muscle show_more_start

  1. Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM. Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. Proc Natl Acad Sci U S A, 2002; 99:15000-5.
  2. Sanoudou D, Kang PB, Haslett JN, Han M, Kunkel LM, Beggs AH. Transcriptional profile of postmortem skeletal muscle. Physiol Genomics. 2004; 16(2): 222-8.
  3. Tomczak KK, Marinescu VD, Ramoni MF, Sanoudou D, Montanaro F, Han M, Kunkel LM, Kohane IS, Beggs AH. Expression profiling and identification of novel genes involved in myogenic differentiation. FASEB J. 2004; 18:403-5.
  4. Liadaki K, Kho AT, Sanoudou D, Schienda J, Flint A, Beggs AH, Kohane IS, Kunkel LM. Side population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers. Exp Cell Res, 2005; 303(2): 360-74.
  5. Kang PB, Kho AT, Sanoudou D, Haslett JN, Dow CP, Han M, Blasko JM, Lidov HG, Beggs AH, Kunkel LM. Variations in gene expression among different types of human skeletal muscle. Muscle Nerve, 2005; 32:483-91.
  6. Cerletti M, Molloy MJ, Tomczak KK, Yoon S, Ramoni MF, Kho AT, Beggs AH, Gussoni E. Melanoma cell adhesion molecule is a novel marker for human fetal myogenic cells and affects myoblast fusion. J Cell Sci, 2006;119: 3117-27.
  7. Moghadaszadeh B, Beggs AH. Selenoproteins and their impact on human health through diverse physiological pathways. Physiology (Bethesda), 2006; 21:307-15. Review.

show_more_end

Alpha-actinins in human normal and disease states show_more_start

  1. North KN, Beggs AH. Deficiency of a skeletal muscle isoform of α-actinin (α-actinin-3) in merosin-positive congenital muscular dystrophy. Neuromuscular Disorders, 1996; 6:229-235.
  2. Vainzof M, Costa CS, Marie SK, Moreira ES, Reed U, Passos-Bueno MR, Beggs AH, Zatz M. Deficiency of α-actinin-3 (ACTN3) occurs in different forms of muscular dystrophy. Neuropediatrics, 1997; 28:223-228.
  3. North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Beggs AH. A common nonsense mutation results in α-actinin-3 deficiency in the general population: evidence for genetic redundancy in humans. Nature Genetics, 1999; 21:353-354.
  4. Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong H-Q, Mathis BJ, Rodriguez-Perez J-C, Allen PG, Beggs AH, Pollak MR. Mutations in ACTN4, encoding α-actinin-4, cause familial focal segmental glomerulosclerosis. Nature Genetics, 2000; 24:251-256.
  5. Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, North K. ACTN3 genotype is associated with human elite athletic performance. American Journal of Human Genetics, 2003; 73: 627-31.

show_more_end

Genetics of congenital myopathies show_more_start

  1. Laing NG, Majda BT, Akkari PA, Layton MG, Mulley JC, Phillips H, Haan EA, White SJ, Beggs AH, Kunkel LM, Groth DM, Boundy KL, Kneebone CS, Blumbergs PC, Wilton SD, Speer MC, Kakulas BA. Assignment of a gene (NEM1) for autosomal dominant nemaline myopathy (MIM # 161800) to chromosome 1. Am J Hum Genet 1992; 50:576-583.
  2. Tahvanaien E, Beggs AH, Wallgren-Pettersson C. Exclusion of two candidate loci as the gene locus for autosomal recessive nemaline myopathy. J Med Genet 1994; 31:79-80.
  3. Wallgren-Pettersson C, Beggs AH, Laing NG. Workshop report: 51st ENMC International Workshop: Nemaline myopathy. 13-15 June 1997, Naarden, The Netherlands. Neuromuscular Disorders, 1998; 8:53-56.
  4. Pelin K, Hilpel P, Donner K, Sewry C, Akkari PA, Wilton SD, Wattanasirichaigoon D, Centner T, Hanefeld H, Odent S, Fardeau M, Urtizberea JA, Muntoni F, Dubowitz V, Beggs AH, Laing NG, Labeit S, de la Chapelle A, Wallgren-Pettersson C. Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Proc Natl Acad Sci, USA 1999; 96:2305-2310.
  5. Nowak KJ, Wattanasirichaigoon D, Goebel HH, Wilce M, Pelin K, Donner K, Jacob RL, Hubner C, Oexle K, Anderson JR, Verity CM, North KN, Iannaccone ST, Muller CR, Nurnberg P, Muntoni F, Sewry C, Hughes I, Stuphen R, Lacson AG, Swoboda KJ, Vigneron J, Wallgren-Pettersson C, Beggs AH, Laing NG. Mutations in the skeletal muscle α-actin gene in patients with actin myopathy and nemaline myopathy. Nature Genetics 1999; 23:208-212.
  6. Wallgren-Pettersson C, Pelin K, Hilpela P, Donner K, Porfirio B, Graziano C, Swoboda KJ, Fardeau M, Urtizberea JA, Muntoni F, Sewry C, Dubowitz V, Iannaccone S, Minetti C, Pedemonte M, Seri M, Cusano R, Lammens M, Castagna-Sloane A, Beggs AH, Laing NG, de la Chapelle A. Clinical and genetic heterogeneity in autosomal recessive nemaline myopathy. Neuromuscular Disorders 1999; 9:564-572.
  7. Ryan MM, Schnell C, Strickland CD, Shield LK, Morgan G, Iannaccone ST, Laing NG, Beggs AH, North KN. Nemaline myopathy: a clinical study of 143 cases. Annal Neurol, 2001; 50:312-320.
  8. Sanoudou D, Beggs, AH. Clinical and genetic heterogenaity in nemaline myopathy, a disease of sarcomeric thin filaments. Trends in Molecular Medicine 2001; 7:362-368.
  9. Wattanasirichaigoon D, Swoboda KJ, Takada F, Tong H-Q, Lip V, Iannaccone ST, Wallgren-Pettersson C, Laing NG, Beggs AH. Mutations of the slow muscle a-tropomyosin gene, TPM3, are a rare cause of nemaline myopathy. Neurology, 2002; 59: 613-617.
  10. Sparrow JC, Nowak KJ, Durling HJ, Beggs AH, Wallgren-Pettersson C, Romero N, Nonaka I, Laing NG. Muscle disease caused by mutations in the skeletal muscle alpha-actin gene (ACTA1). Neuromuscular Disorders, 2003; 13: 519-31. Review.
  11. Agrawal PB, Strickland CD, Midgett C, Morales A, Newburger DE, Poulos MA, Tomczak KK, Ryan MM, Iannaccone ST, Crawford TO, Laing NG, Beggs AH. Heterogeneity of nemaline myopathy cases with skeletal muscle alpha-actin gene mutations. Annals of Neurology, 2004; 56: 86-96.
  12. Wallgren-Pettersson C, Pelin K, Nowak KJ, Muntoni F, Romero NB, Goebel HH, North KN, Beggs AH, Laing NG; ENMC International Consortium On Nemaline Myopathy. Genotype-phenotype correlations in nemaline myopathy caused by mutations in the genes for nebulin and skeletal muscle alpha-actin. Neuromuscular Disorders, 2004: 14: 461-70.
  13. Bitoun M, Maugenre S, Jeannet PY, Lacene E, Ferrer X, Laforet P, Martin JJ, Laporte J, Lochmuller H, Beggs AH, Fardeau M, Eymard B, Romero NB, Guicheney P. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nature Genetics, 2005: 37: 1207-9.
  14. Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari VL, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR, Beggs AH. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. The American Journal Human Genetics, 2007; 80: 162-7.

show_more_end

Gene expression studies of normal and diseased muscles show_more_start

  1. Greenberg SA, Sanoudou D, Haslett JN, Kohane IS, Kunkel LM, Beggs AH, Amato AA. Molecular profiles of inflammatory myopathies. Neurology, 2002; 59:1170-82.
  2. Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM. Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. Proc Natl Acad Sci U S A. 2002; 99:15000-5.
  3. Sanoudou D, Haslett JN, Kho AT, Guo S, Gazda HT, Greenberg SA, Lidov HG, Kohane IS, Kunkel LM, Beggs AH. Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle. Proc Natl Acad Sci U S A, 2003 Apr 15;100(8):4666-71.
  4. Tomczak KK, Marinescu VD, Ramoni MF, Sanoudou D, Montanaro F, Han M, Kunkel LM, Kohane IS, Beggs AH. Expression profiling and identification of novel genes involved in myogenic differentiation. FASEB J, 2004;18:403-5.
  5. Sanoudou D, Frieden LA, Haslett JN, Kho AT, Greenberg SA, Kohane IS, Kunkel LM, Beggs AH. Molecular classification of nemaline myopathies: "nontyping" specimens exhibit unique patterns of gene expression. Neurobiology of Disease. 2004;15:590-600.
  6. Kang PB, Kho AT, Sanoudou D, Haslett JN, Dow CP, Han M, Blasko JM, Lidov HG, Beggs AH, Kunkel LM. Variations in gene expression among different types of human skeletal muscle. Muscle Nerve, 2005; 32: 483-91.
  7. Haslett JN, Kang PB, Han M, Kho AT, Sanoudou D, Volinski JM, Beggs AH, Kohane IS, Kunkel LM. The influence of muscle type and dystrophin deficiency on murine expression profiles. Mamm Genome. 2005;16:739-48.
  8. Sanoudou D, Corbett MA, Han M, Ghoddusi M, Nguyen MA, Vlahovich N, Hardeman EC, Beggs AH. Skeletal muscle repair in a mouse model of nemaline myopathy. Hum Mol Genet, 2006; 15: 2603-12.

show_more_end

Pathophysiology of congenital myopathies show_more_start

  1. Bonnemann CG, Thompson TG, van der Ven PF, Goebel HH, Warlo I, Vollmers B, Reimann J, Herms J, Gautel M, Takada F, Beggs AH, Furst DO, Kunkel LM, Hanefeld F, Schroder R. Filamin C accumulation is a strong but nonspecific immunohistochemical marker of core formation in muscle. J Neurol Sci, 2003; 206:71-8.
  2. Ryan MM, Ilkovski B, Strickland CD, Schnell C, Sanoudou D, Midgett C, Houston R, Muirhead D, Dennett X, Shield LK, De Girolami U, Iannaccone ST, Laing NG, North KN, Beggs AH. Clinical course correlates poorly with muscle pathology in nemaline myopathy. Neurology. 2003; 60:665-73.
  3. Sanoudou D, Haslett JN, Kho AT, Guo S, Gazda HT, Greenberg SA, Lidov HG, Kohane IS, Kunkel LM, Beggs AH. Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle. Proc Natl Acad Sci U S A, 2003; 100:4666-71.
  4. Gurgel-Giannetti J, Reed UC, Marie SK, Zanoteli E, Fireman MA, Oliveira AS, Werneck LC, Beggs AH, Zatz M, Vainzof M. Rod distribution and muscle fiber type modification in the progression of nemaline myopathy. J Child Neurol, 2003; 18:235-40.
  5. Sanoudou D, Frieden LA, Haslett JN, Kho AT, Greenberg SA, Kohane IS, Kunkel LM, Beggs AH. Molecular classification of nemaline myopathies: "nontyping" specimens exhibit unique patterns of gene expression. Neurobiol Dis. 2004; 15:590-600.
  6. Pierson CR, Tomczak K, Agrawal P, Moghadaszadeh B, Beggs AH. X-linked myotubular entronuclear myopathies. J Neuropathol Exp Neurol, 2005; 64: 555-64. Review.
  7. Keller CE, Hays AP, Rowland LP, Moghadaszadeh B, Beggs AH, Bhagat G. Adult-onset nemaline myopathy and monoclonal gammopathy. Arch Neurol, 2006; 63:132-4.
  8. Sanoudou D, Corbett MA, Han M, Ghoddusi M, Nguyen MA, Vlahovich N, Hardeman EC, Beggs AH. Skeletal muscle repair in a mouse model of nemaline myopathy. Hum Mol Genet, 2006; 15: 2603-12.
  9. Pierson CR, Agrawal PB, Blasko J, Beggs AH. Myofiber size correlates with MTM1 mutation type and outcome in X-linked myotubular myopathy. Neuromuscular Disorders, 2007; 17: 562-568

show_more_end

Genetics of Duchenne/Becker and other muscular dystrophies show_more_start

  1. Koenig M, Beggs AH, Moyer M, et al. The molecular basis of Duchenne versus Becker muscular dystrophy: Correlation of severity with type of deletion. The American Journal of Human Genetics, 1989; 45:498-506.
  2. Hoffman EP, Beggs AH, Koenig M, Kunkel LM, Angelini C. Cross-reactive protein in Duchenne muscle. Lancet, 1989; ii:1211-1212.
  3. Beggs AH, Kunkel LM. Improved diagnosis of Duchenne/Becker muscular dystrophy. J Clin Invest, 1990; 85:613-619.
  4. Angelini C, Beggs AH, Hoffman EP, Fanin M, Kunkel LM. Enormous dystrophin in a patient with Becker muscular dystrophy. Neurology, 1990; 40:808-812.
  5. Beggs AH, Kunkel LM. A polymorphic CACA repeat in the 3' untranslated region of dystrophin. Nucleic Acids Research, 1990; 18:1931.
  6. Sklar RM, Beggs AH, Lev AA, Specht L, Shapiro F, Brown RH. Defective dystrophin in Duchenne and Becker dystrophy myotubes in cell culture. Neurology, 1990; 40:1854-1858.
  7. Beggs AH, Koenig M, Boyce FM, Kunkel LM. Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Human Genetics 1990; 86:45-48.
  8. Boyce FM, Beggs AH, Feener C, Kunkel LM. Dystrophin is transcribed in brain from a distant upstream promoter. Proc Natl Acad Sci USA, 1991; 88:1276-1280.
  9. Arahata K, Beggs AH, Honda H, Ito S, Ishiura S, Tsukahara T, Ishiguro T, Eguchi C, Orimo S, Arikawa E, Kaido M, Nonaka I, Sugita H, Kunkel LM. Preservation of the C-terminus of dystrophin molecule in the skeletal muscle from Becker muscular dystrophy. J Neurol Sci, 1991; 101:148-156.
  10. Beggs AH, Hoffman EP, Snyder JR, Arahata K, Specht L, Shapiro F, Angelini C, Sugita H, Kunkel LM. Exploring the molecular basis for variability among patients with Becker muscular dystrophy: Dystrophin gene and protein studies. Am J Hum Genet, 1991; 49:54-67.
  11. Beggs AH, Neumann PE, Arahata K, Arikawa E, Nonaka I, Anderson MD, Kunkel LM. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy. Proc Natl Acad Sci USA, 1992; 89:623-627.
  12. Byers TJ, Neumann PE, Beggs AH, Kunkel LM. ELISA quantitation of dystrophin for the diagnosis of Duchenne and Becker muscular dystrophies. Neurology, 1992; 42:570-576.
  13. Miller G, Beggs AH, Towfighi J. Early onset autosomal dominant progressive muscular dystrophy presenting in childhood as a Becker phenotype - the importance of dystrophin and molecular genetic analysis. Neuromuscular Disorders, 1992; 2:121-124.
  14. Beggs AH, Hoffman EP, Kunkel LM. Additional dystrophin fragment in Becker muscular dystrophy may result from proteolytic cleavage at deletion junctions. Am J Med Genet, 1992; 44:378-381.
  15. Specht LA, Beggs AH, Korf B, Kunkel LM, Shapiro F. Prediction of dystrophin phenotype by DNA analysis in Duchenne/Becker muscular dystrophy. Pediatr Neurol, 1992; 8:432-436.
  16. Michels VV, Pastores GM, Schaid DJ, Moll PP, Driscoll DJ, Miller FA, Burnett JC, Rodeheffer RJ, Tajik JA, Beggs AH, Kunkel LM, Thibodeau SN. Dystrophin analysis in idiopathic dilated cardiomyopathy. Journal of Medical Genetics, 1993; 30:955-957.
  17. Beggs AH. Multiplex PCR for identification of dystrophin gene deletions in patients with Duchenne and Becker muscular dystrophy. In: Current Protocols in Human Genetics. Dracopoli N, Haines J, Korf B, Moir D, Smith D, Morton C, Seidman C, Seidman J, eds. Wiley Interscience. 1994.
  18. Arikawa-Hirasawa E, Koga R, Tsukahara T, Nonaka I, Mitsudome A, Goto K, Beggs AH, Arahata K. A severe muscular dystrophy patient with an internally deleted very short (110kD) dystrophin: Presence of the binding site for dystrophin-associated glycoprotein (DAG) may not be enough for physiological function of dystrophin. Neuromuscular Disorders, 1995; 5:429-438.
  19. North KN, Miller G, Iannaccone ST, Clemens PR, Chad DA, Bella I, Smith TW, Beggs AH, Specht LA. Cognitive dysfunction as the major presenting feature of Becker's Muscular Dystrophy. Neurology, 1996; 46:461-465.
  20. North KN, Specht LA, Sethi RK, Shapiro F, Beggs AH. Congenital muscular dystrophy associated with merosin deficiency. J Child Neurol, 1996; 11:291-295.
  21. Khurana TS, Specht LA, Beggs AH, Tome FMS, Letureq F, Chevallay M, Chafey P, Kunkel LM. The concomitant use of dystrophin and utrophin/dystrophin related protein antibodies to reduce misdiagnosis of Duchenne/Becker muscular dystrophy. Biochem Biophys Res Comm, 1997; 241:232-235.
  22. Beggs, AH. Dystrophinopathy, the expanding phenotype: Dystrophin abnormalities in X-linked dilated cardiomyopathy. Editorial in Circulation, 1997; 95:2344-2347.
  23. Vainzof M, Moreira ES, Suzuki OT, Faulkner MRG, Valle G, Beggs AH, Carpen O, Ribeiro AF, Zanoteli E, Gurgel-Gianneti J, Tsanaclis AM, Silva HC, Passos-Bueno MR, Zatz M. Telethonin protein expression in neuromuscular disorders. Biochem Biophys Acta, 2002, 1588: 33-40.

show_more_end

Genetic mapping studies of hereditary disorders of muscle show_more_start

  1. Engle EC. Kunkel LM, Specht LA, Beggs AH. Mapping a gene for Congenital Fibrosis of the Extraocular Muscles to the centromeric region of chromosome 12.Nature Genetics, 1994; 7:69-73.
  2. Engle EC, Marondel I, Houtman WA, de Vries B, Lowenstein A, Lazar M, Ward DC, Kucherlapati R, Beggs AH. Congenital fibrosis of the extraocular muscles (autosomal dominant congenital external ophthalmoplegia): genetic homogeneity, linkage refinement and physical mapping on chromosome 12. The American Journal of Human Genetics, 1995; 57:1086-1094.
  3. Engle EC, Gumnerov BC, McKeown CA, Schatz M, Johns DR, Porter JD, Beggs AH. Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles. Annals of Neurology, 1997; 41:314-325.
  4. Engle EC, Castro A, Macy M, Knoll, JHM, Beggs AH. A gene for isolated congenital ptosis maps to a 3 cM region within 1p32-p34.1. The American Journal of Human Genetics, 1997; 60:1150-1157.
  5. Wang SM, Zwaan J, Mullaney PB, Jabak MH, Al-Awad A, Beggs AH, Engle EC. Congenital fibrosis of the extraocular muscles type 2, an inherited exotropic strabismus fixus, maps to distal 11q13. The American Journal of Human Genetics, 1998; 63:517-525.
  6. Zervos A, Hunt KE, Tong H-Q, Avallone J, Morales J, Friedman N, Cohen BH, Clark B, Guo S, Gazda H, Beggs AH, Traboulsi EI. Clinical, genetic and histopathologic findings in two siblings with muscle-eye-brain disease. Euro J Ophthal, 2002; 12: 253-261.

show_more_end

Genetics of Diamond Blackfan Anemia show_more_start

  1. Gazda HT, Lipton JM, Willig T, Ball S, Niemeyer CM, Tchernia G, Mohandas N, Daly MJ, Ploszynska D, Webber A, Viskochil DH, Nathan DG, Beggs AH, and Sieff CA. Evidence for Linkage of familial Diamond-Blackfan anemia to Chromosome 8p23.3-p22 and for non-19q non-8p disease. Blood, 2001; 97:2145-2150.
  2. Gazda HT, Zhong R, Long L, Niewiadomska E, Lipton JM, Ploszynska A, Zaucha JM, Vlachos A, Atsidaftos E, Viskochil DH, Niemeyer CM, Meerpohl JJ, Rokicka-Milewska R, Pospisilova D, Wiktor-Jedrzejczak W, Nathan DG, Beggs AH, Sieff CA. RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations. British Journal of Haematology, 2004; 27(1):105-13.
  3. Gazda HT, Kho AT, Sanoudou D, Zaucha JM, Kohane IS, Sieff CA, Beggs AH. Defective ribosomal protein gene expression alters transcription, translation, apoptosis, and oncogenic pathways in Diamond-Blackfan anemia. Stem Cells, 2006; 24:2034-44.
  4. Gazda HT, Grabowska A, Merida-Long LB, Latawiec E, Schneider HE, Lipton JM, Vlachos A, Atsidaftos E, Ball SE, Orfali KA, Niewiadomska E, Da Costa L, Tchernia G, Niemeyer C, Meerpohl JJ, Stahl J, Schratt G, Glader B, Backer K, Wong C, Nathan DG, Beggs AH, Sieff CA. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. The American Journal of Human Genetics, 2006; 79:1110-8.

show_more_end

Genetics of an inherited cardiac arrhythmia, long QT syndrome show_more_start

  1. Duggal P, Vesely MR, Wattanasirichaigoon D, Villafane J, Kaushik V, Beggs AH. Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano Ward forms of long QT syndrome. Circulation, 1998; 97:142-146.
  2. Satler CA, Vesely MR, Duggal P, Ginsburg GS, Beggs AH. Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome.Human Genetics, 1998;102:265-272.
  3. Wattanasirichaigoon D, Beggs AH. Molecular genetics of long-QT syndrome. Current Opinion in Pediatrics, 1998; 10:628-634.
  4. Wattanasirichaigoon D, Vesely MR, Duggal P, Levine JC, Blume ED, Wolff GS, Edwards SB, Beggs AH. Sodium Channel abnormalities are infrequent in patients with long QT syndrome: Identification of two novel SCN5A mutations. Am J Med Genet, 1999; 86:470-476.
  5. Schwartz PJ, Priori SG, Spazzolini C, Moss AJ, Vincent GM, Napolitano C, Denjoy I, Guicheney P, Breithardt G, Keating MT, Towbin JA, Beggs AH, Brink P, Wilde AAM, Toivonen L, Zareba W, Robinson JL, Timothy KW, Corfield V, Wattanasirichaigoon D, Corbett C, Haverkamp W, Schulze-Bahr E, Lehmann MH, Schwartz K, Coumel P, Bloise B. Genotype-Phenotype Correlation in the Long-QT Syndrome : Gene-Specific Triggers for Life-Threatening Arrhythmias. Circulation, 2001; 103: 89-95.
  6. Splawski I, Timothy KW, Tateyama M, Clancy CE, Malhotra A, Beggs AH, Cappuccio FP, Sagnella GA, Kass RS, Keating MT. Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science, 2002; 297:1333-6.
  7. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A, 2005;102:8089-96; discussion 8086-8.

show_more_end

Collaborations on other genes, proteins and diseases show_more_start

  1. Passos-Bueno MR, Byth B, Basset JHD, Rosenberg S, Takata RI, Bakker E, Beggs AH, Pavanello RC, Vainzof M, Davies KE, Zatz M. Severe nonspecific X-linked mental retardation caused by a proximally Xp located gene: intragenic heterogeneity or a new form of X-linked mental retardation? Am Journal of Medical Genetics, 1993; 46:172-175.
  2. Zhu J, Leon SP, Beggs AH, Busque L, Gilliland DG, Black PM. Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus. J Clin Endocrin Metab, 1994; 78:922-927.
  3. Azim AC, Knoll JHM, Beggs AH, Chishti AH. Isoform cloning, actin binding, and chromosomal localization of human erythroid dematin, a member of the villin superfamily. J Biol Chem, 1995; 270:17407-17413.
  4. Zhu J, Frosch MP, Busque L, Beggs AH, Dashner K, Gilliland DG, Black PM. Analysis of meningiomas by methylation- and transcription-based clonality assays. Cancer Research, 1995; 55:3865-3872.
  5. Byers TJ, Beggs AH, McNally EM, Kunkel LM. Novel actin crosslinker superfamily member identified by a two step degenerate PCR procedure. FEBS letters, 1995; 368:500-504.
  6. Zhu J, Guo S-Z, Beggs AH, Maruyama T, Santarius T, Dashner K, Olson N, Wu JK, Black PM. Microsatellite instability analysis of primary human brain tumors.Oncogene, 1996; 12:1417-1423.
  7. Scharf JM, Damron D, Frisella A, Bruno S, Beggs AH, Kunkel LM, Dietrich WF. The mouse region syntenic for human spinal muscular atrophy lies within the Lgn1 critical interval and contains multiple copies of Naip exon 5. Genomics, 1996; 38:405-417.
  8. Gazda H, Lipton JM, Willig T-N, Ball S, Niemeyer CM, Tchernia G, Mohandas N, Daly MJ, Ploszynska A, Orfali KA, Vlachos A, Glader BE, Rokicka-Milewska R, Ohara A, Baker D, Pospisilova D, Weber A, Viskochil DH, Nathan DG, Beggs AH, Sieff CA. Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease. Blood, 2001; 97:2145-2150.
  9. Mizuno Y, Puca AA, O'Brien KF, Beggs AH, Kunkel LM. Genomic organization and single-nucleotide polymorphism map of desmuslin, a novel intermediate filament protein on chromosome 15q26.3. BMC Genetics, 2001; 2:8.

show_more_end

For a current, complete un-annotated listing of Beggs Lab papers, please search Pub Med for Beggs, AH.

The future of pediatrics will be forged by thinking differently, breaking paradigms and joining together in a shared vision of tackling the toughest challenges before us.”
- Sandra L. Fenwick, President and CEO
Close