Research Topics
Genomes and GenesSpecies | James GusellaSummaryAffiliation: Harvard University Country: USA Publications
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Publications
No post-genetics era in human disease researchJames Gusella
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Nat Rev Genet 3:72-9. 2002..In the post-genomics era, genetics is fundamental to understanding disease at all stages of the pathogenic process...- Rescue of a human mRNA splicing defect by the plant cytokinin kinetinSusan A Slaugenhaupt
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
Hum Mol Genet 13:429-36. 2004..Further, kinetin should be explored as a treatment for increasing the level of normal IKAP in FD, and for other splicing disorders that may share a similar mechanism... 
A novel approach to investigate tissue-specific trinucleotide repeat instabilityJong Min Lee
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA
BMC Syst Biol 4:29. 2010..However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors...- The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factorHiroki Takano
Molecular Neurogenetics Unit, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, MGH East Building 149, 13th Street, Charlestown, Massachusetts 02129, USA
BMC Neurosci 3:15. 2002.... - Reversal of a full-length mutant huntingtin neuronal cell phenotype by chemical inhibitors of polyglutamine-mediated aggregationJin Wang
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02129, USA
BMC Neurosci 6:1. 2005.... - Genetic analysis of the GRIK2 modifier effect in Huntington's diseaseWenqi Zeng
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
BMC Neurosci 7:62. 2006.... - Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS studyJian Liang Li
Department of Neurology, Boston University School of Medicine, Boston, MA, USA
BMC Med Genet 7:71. 2006.... - Genomewide association study for onset age in Parkinson diseaseJeanne C Latourelle
Boston University School of Medicine, Boston, MA, USA
BMC Med Genet 10:98. 2009..There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age... - The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD studyJeanne C Latourelle
Department of Neurology, Boston University School of Medicine, Boston University, Boston, MA, USA
BMC Med 6:32. 2008..Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD... - Genetic criteria for Huntington's disease pathogenesisJames F Gusella
Center for Human Genetic Research, Massachusetts General Hospital, CPZN 5830, Boston, MA 02114, USA
Brain Res Bull 72:78-82. 2007.... - Huntington's disease: the case for genetic modifiersJames F Gusella
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 02114, USA
Genome Med 1:80. 2009.... - Huntingtin: a single bait hooks many speciesJ F Gusella
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
Curr Opin Neurobiol 8:425-30. 1998..Recent protein trapping to identify huntingtin interactors now reveals that many different prey fall victim to huntingtin bait... - Genomic profiling distinguishes familial multiple and sporadic multiple meningiomasYiping Shen
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, 02114, USA
BMC Med Genomics 2:42. 2009.... - Huntington's disease: seeing the pathogenic process through a genetic lensJames F Gusella
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Richard B Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA
Trends Biochem Sci 31:533-40. 2006.... - Molecular genetics: unmasking polyglutamine triggers in neurodegenerative diseaseJ F Gusella
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
Nat Rev Neurosci 1:109-15. 2000.... - Merlin: the neurofibromatosis 2 tumor suppressorJ F Gusella
Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston 02114, USA
Biochim Biophys Acta 1423:M29-36. 1999..Consequently, the disruptions due to merlin inactivation in the progression of malignant mesothelioma may represent a tumor suppressor role operating by a different pathway than that in schwannoma or meningioma... - Expanding the notion of disease in Huntington's diseaseJames F Gusella
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
Biol Psychiatry 62:1340. 2007 - Inactivation patterns of NF2 and DAL-1/4.1B (EPB41L3) in sporadic meningiomaFabio Nunes
Department of Neurology, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
Cancer Genet Cytogenet 162:135-9. 2005..Furthermore, we found the majority of meningiomas developed monosomy rather than isodisomy at the NF2 and DAL-1/4.1B loci as the mechanism for LOH... - Prevalence of incompletely penetrant Huntington's disease alleles among individuals with major depressive disorderRoy H Perlis
Center for Human Genetic Research and the Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA
Am J Psychiatry 167:574-9. 2010..However, the prevalence of HTT CAG repeat expansions among individuals diagnosed with major depressive disorder has not been established... - Screening for familial APP mutations in sporadic cerebral amyloid angiopathyAlessandro Biffi
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
PLoS ONE 5:e13949. 2010..The majority of affected families harbor mutations in the Beta amyloid Peptide (Aβ) coding region of the gene for amyloid precursor protein (APP) or have duplications of chromosomal segments containing APP... - A genome-wide linkage and association scan reveals novel loci for autismLauren A Weiss
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
Nature 461:802-8. 2009..The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants... 
Association of a polymorphism near CREB1 with differential aversion processing in the insula of healthy participantsRoy H Perlis
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Arch Gen Psychiatry 65:882-92. 2008....- Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington's diseaseShotaro Kishikawa
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, and Department of Neurology, Boston University School of Medicine, MA 02114, USA
Neurobiol Dis 24:280-5. 2006..These results indicate that BDNF does not influence significantly the mechanisms in HD pathogenesis that lead to neurologic onset... - Therapeutic potential and mechanism of kinetin as a treatment for the human splicing disease familial dysautonomiaMatthew M Hims
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
J Mol Med (Berl) 85:149-61. 2007..Lastly, we highlight the potential of kinetin for the treatment of other human splicing disorders by showing correction of a splicing defect in neurofibromatosis... - X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairmentLeanne M Dibbens
Department of Genetic Medicine, Level 9 Rieger Building, Women s and Children s Hospital, 72 King William Road, North Adelaide, South Australia 5006, Australia
Nat Genet 40:776-81. 2008..PCDH19 is expressed in developing brains of human and mouse and is the first member of the cadherin superfamily to be directly implicated in epilepsy or mental retardation... - A humanized IKBKAP transgenic mouse models a tissue-specific human splicing defectMatthew M Hims
Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
Genomics 90:389-96. 2007..Last, these mice will permit direct studies of tissue-specific splicing and the identification of regulatory factors that play a role in complex gene expression... - Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolismJong Min Lee
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
PLoS Genet 3:e135. 2007..Elucidation of this HD CAG-dependent pathway would spur efforts to achieve energy-based therapeutics in HD... - Familial dysautonomiaSusan A Slaugenhaupt
Harvard Institute of Human Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
Curr Opin Genet Dev 12:307-11. 2002..IKAP, the IKBKAP-encoded protein, is a member of the recently identified human Elongator complex. The major FD mutation is a splice mutation that results in aberrant tissue-specific mRNA splicing... - HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolismIhn Sik Seong
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Richard B Simches Research Center, Boston, MA 02114, USA
Hum Mol Genet 14:2871-80. 2005..Moreover, the evidence that this polymorphism can determine energy status in the non-HD range suggests that it should be tested as a potential physiological modifier in both health and disease... - Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in miceElisa Fossale
Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
Hum Mol Genet 11:2233-41. 2002..These findings, therefore, support a chronic impact of mutant huntingtin on an essential ribosomal regulatory gene to be investigated for its role very early in HD pathogenesis... - Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomiaMath P Cuajungco
Harvard Institute of Human Genetics, Harvard Medical School, Boston, MA, USA
Am J Hum Genet 72:749-58. 2003..Therefore, exploration of methods to increase the WT:MU IKBKAP transcript ratio in the nervous system offers a promising approach for developing an effective therapy for patients with FD... - Candidate DNA replication initiation regions at human trinucleotide repeat disease lociTaurai Nenguke
Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089-1340, USA
Hum Mol Genet 12:1021-8. 2003..Comparison with experimental results from model systems suggests that a complex relationship may exist between instability and the proximity and/or orientation of the repeats with respect to an IR... - Huntington's diseaseMarcy E MacDonald
Molecular Neurogenetics Unit, Center for Human Genetics Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
Neuromolecular Med 4:7-20. 2003.... - The GPR54 gene as a regulator of pubertyStephanie B Seminara
Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA
N Engl J Med 349:1614-27. 2003..We conducted studies in humans and mice to identify the genetic factors that determine the onset of puberty... - Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in miceVanessa C Wheeler
Molecular Neurogenetics Unit and Molecular Neuropathology, Massachusetts General Hospital, Charlestown, MA 02129, USA
Hum Mol Genet 11:633-40. 2002..Thus, potential HD therapies in man might be directed at different levels: preventing the disease-initiating mechanism or slowing the subsequent progression of pathogenesis... - Modified single-stranded oligonucleotides inhibit aggregate formation and toxicity induced by expanded polyglutamineHetal Parekh-Olmedo
Department of Biological Sciences, University of Delaware, Delaware Biotechnology Institute, Newark, DE 19711, USA
J Mol Neurosci 24:257-67. 2004..Our data provide the first evidence that short synthetic oligonucleotides inhibit a fundamental pathological pathway of HD and may provide the basis for a novel therapeutic approach... - Linkage of eye movement dysfunction to chromosome 6p in schizophrenia: additional evidenceSteven Matthysse
Psychology Research Laboratory, Mailman Research Center, McLean Hospital Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
Am J Med Genet B Neuropsychiatr Genet 128:30-6. 2004..1996, 1999]. We regard our results as independent evidence supporting the findings of Arolt et al. [1996, 1999] and also as support for the L.T. model as a way of combining the traits ETD and schizophrenia... - Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD studyMei Sun
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA
Arch Neurol 63:826-32. 2006..The PARK2 gene at 6q26 encodes parkin, whose inactivation is implicated in an early-onset autosomal recessive form of Parkinson disease (PD)... - Identification of the first non-Jewish mutation in familial DysautonomiaMaire Leyne
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, USA
Am J Med Genet A 118:305-8. 2003..In light of this fact, the diagnostic criteria for FD must be expanded. Furthermore, in order to ensure carrier identification in all ethnicities, this mutation must now be considered when screening for FD... - Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in miceSilvia Gines
Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th St, Charlestown, MA 02129, USA
Hum Mol Genet 12:497-508. 2003.... - The NF2 tumor suppressor Merlin and the ERM proteins interact with N-WASP and regulate its actin polymerization functionNitasha Manchanda
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
J Biol Chem 280:12517-22. 2005..This novel function of merlin and the ERMs illustrates a mechanism by which these proteins directly exert their effects on actin reorganization and also provides new insight into N-WASP regulation... - Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3Wen Qi Zeng
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Charlestown, MA 02129 2000, USA
Am J Hum Genet 77:16-26. 2005.... - PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD studyAnita L Destefano
Department of Neurology, Boston University Schools of Medicine and of Public Health, Boston, MA 02118, USA
Am J Hum Genet 70:1089-95. 2002.... - Human chromosome 7: DNA sequence and biologyStephen W Scherer
Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8
Science 300:767-72. 2003..This approach enabled the discovery of candidate genes for developmental diseases including autism... - Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndromeHyung Goo Kim
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA
Am J Hum Genet 83:511-9. 2008..Our findings indicate that both normosmic IHH and KS are mild allelic variants of CHARGE syndrome and are caused by CHD7 mutations... - Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolateIrene Pichler
Institute of Genetic Medicine, European Academy, Bolzano, Italy
Am J Hum Genet 79:716-23. 2006..1). These findings reemphasize the genetic heterogeneity of the disorder and strongly support the identification of a novel locus for RLS on chromosome 2q... - A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS studyJian-Liang Li
Department of Neurology, Boston University School of Medicine, and Bioinformatics Program, School of Public Health, Boston University, Boston, MA, USA
Am J Hum Genet 73:682-7. 2003..Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD... - Association between microdeletion and microduplication at 16p11.2 and autismLauren A Weiss
Autism Consortium, Boston, USA
N Engl J Med 358:667-75. 2008..Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role... - The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onsetJ Michael Andresen
Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, USA
Ann Hum Genet 71:295-301. 2007..27, P= 2 x 10(-16)]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range... - Is the disruption of an N-myristoyltransferase (NMT2) associated with hypoplastic testes?Fabiola Quintero-Rivera
Massachusetts General Hospital, Center for Human Genetic Research, Boston, Massachusetts, USA
Am J Med Genet A 143:1796-8. 2007 - NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defectsWeining Lu
Genetics Division, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
PLoS Genet 3:e80. 2007.... - Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral refluxWeining Lu
Genetics Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Am J Hum Genet 80:616-32. 2007..Adult heterozygous and mosaic mutant mice with reduced Robo2 gene dosage also exhibit striking CAKUT-VUR phenotypes. Collectively, these results implicate the SLIT-ROBO signaling pathway in the pathogenesis of a subset of human VUR... - Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16Luc Djousse
Evans Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USA
Neurogenetics 5:109-14. 2004..Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker...
Research Grants
- HUNTINGTON'S DISEASE CENTER WITHOUT WALLSJames Gusella; Fiscal Year: 2007..which has made a major organizational and financial commitment to capitalize on basic science findings from academic studies such as those of this long-standing HD Center. ..
- MECHANISM OF FAMILIAL DYSAUTONOMIAJames Gusella; Fiscal Year: 2002....
- MECHANISM OF FAMILIAL DYSAUTONOMIAJames Gusella; Fiscal Year: 1999....
- Vitamin D Hormone: Function and Mechanism of ActionSYLVIA S CHRISTAKOS; Fiscal Year: 2010....