Complete genomic screen in Parkinson disease: evidence for multiple genes.
William K. Scott,Martha Nance,Ray L. Watts,Jean P. Hubble,William C. Koller,Kelly E. Lyons,Rajesh Pahwa,Matthew B. Stern,Amy Colcher,Bradley C. Hiner,Joseph Jankovic,William G. Ondo,Fred H. Allen,Christopher G. Goetz,Gary W. Small,Donna Masterman,Frank L. Mastaglia,Nigel G. Laing,Jeffrey M. Stajich,Brandon D. Slotterbeck,Michael W. Booze,Robert C. Ribble,Evadnie Rampersaud,Sandra G. West,Rachel A. Gibson,Lefkos T. Middleton,Allen D. Roses,Jonathan L. Haines,Burton L. Scott,Jeffery M. Vance,Margaret A. Pericak-Vance +30 more
Reads0
Chats0
TLDR
The data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-ONSet PD.Abstract:
ContextThe relative contribution of
genes
vs environment in idiopathic Parkinson
disease (PD) is controversial. Although genetic studies have identified 2
genes in which
mutations cause rare single-gene variants of PD and observational
studies have suggested a genetic component, twin studies have suggested that
little genetic contribution exists in the common forms of PD.ObjectiveTo identify genetic risk factors for idiopathic PD.Design, Setting, and ParticipantsGenetic
linkage study conducted 1995-2000 in which a complete
genomic screen (n = 344 markers) was performed in 174 families with multiple individuals
diagnosed as having idiopathic PD, identified through probands in 13 clinic
populations in the continental United States and Australia. A total of 870
family members were studied: 378 diagnosed as having PD, 379 unaffected by
PD, and 113 with unclear status.Main Outcome MeasuresLogarithm of odds (lod) scores generated from
parametric and nonparametric genetic linkage analysis.ResultsTwo-point parametric maximum parametric lod score (MLOD) and multipoint
nonparametric lod score (LOD) linkage analysis detected significant evidence
for linkage to 5 distinct chromosomal regions:
chromosome 6 in the parkin
gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with
PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62),
8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and
in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59)
in families with both levodopa-responsive and levodopa-nonresponsive patients.ConclusionsOur data suggest that the parkin gene is important in early-onset PD
and that multiple genetic factors may be important in the development of idiopathic
late-onset PD.read more
Citations
More filters
Journal ArticleDOI
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
Jean-Charles Lambert,Jean-Charles Lambert,Jean-Charles Lambert,Carla A. Ibrahim-Verbaas,Denise Harold,Adam C. Naj,Rebecca Sims,Céline Bellenguez,Céline Bellenguez,Céline Bellenguez,Gyungah Jun,Anita L. DeStefano,Joshua C. Bis,Gary W. Beecham,Benjamin Grenier-Boley,Benjamin Grenier-Boley,Benjamin Grenier-Boley,Giancarlo Russo,Tricia A. Thornton-Wells,Nicola Jones,Albert V. Smith,Vincent Chouraki,Vincent Chouraki,Vincent Chouraki,Charlene Thomas,M. Arfan Ikram,Diana Zelenika,Badri N. Vardarajan,Yoichiro Kamatani,Chiao-Feng Lin,Amy Gerrish,Helena Schmidt,Brian W. Kunkle,Melanie L. Dunstan,Agustín Ruiz,Marie-Thérèse Bihoreau,Seung Hoan Choi,Christiane Reitz,Florence Pasquier,Paul Hollingworth,Alfredo Ramirez,Olivier Hanon,Annette L. Fitzpatrick,Joseph D. Buxbaum,Dominique Campion,Paul K. Crane,Clinton T. Baldwin,Tim Becker,Tim Becker,Vilmundur Gudnason,Carlos Cruchaga,David Craig,Najaf Amin,Claudine Berr,Oscar L. Lopez,Philip L. De Jager,Philip L. De Jager,Vincent Deramecourt,Janet A. Johnston,Denis A. Evans,Simon Lovestone,Luc Letenneur,Francisco J. Morón,David C. Rubinsztein,Gudny Eiriksdottir,Kristel Sleegers,Kristel Sleegers,Alison Goate,Nathalie Fievet,Nathalie Fievet,Matthew J. Huentelman,Michael Gill,Kristelle Brown,M. Ilyas Kamboh,Lina Keller,Pascale Barberger-Gateau,Bernadette McGuinness,Eric B. Larson,Eric B. Larson,Robert C. Green,Amanda J. Myers,Carole Dufouil,Stephen Todd,David Wallon,Seth Love,Ekaterina Rogaeva,John Gallacher,Peter St George-Hyslop,Peter St George-Hyslop,Jordi Clarimón,Alberto Lleó,Anthony Bayer,Debby W. Tsuang,Lei Yu,Magda Tsolaki,Paola Bossù,Gianfranco Spalletta,Petroula Proitsi,John Collinge,Sandro Sorbi,Florentino Sanchez-Garcia,Nick C. Fox,John Hardy,Maria Candida Deniz Naranjo,Paolo Bosco,Robert Clarke,Carol Brayne,Daniela Galimberti,Michelangelo Mancuso,Fiona E. Matthews,Genetic,Environmental Risk in Alzheimer's Disease,Environmental Risk in Alzheimer's Disease,Cohorts for Heart,Cohorts for Heart,Susanne Moebus,Patrizia Mecocci,Maria Del Zompo,Wolfgang Maier,Wolfgang Maier,Harald Hampel,Harald Hampel,Alberto Pilotto,María J. Bullido,María J. Bullido,Francesco Panza,Paolo Caffarra,Paolo Caffarra,Benedetta Nacmias,John R. Gilbert,Manuel Mayhaus,Lars Lannfelt,Hakon Hakonarson,Sabrina Pichler,Minerva M. Carrasquillo,Martin Ingelsson,Duane Beekly,Victoria Alvarez,Fanggeng Zou,Otto Valladares,Steven G. Younkin,Eliecer Coto,Kara L. Hamilton-Nelson,Wei Gu,Cristina Razquin,Pau Pastor,Ignacio Mateo,Michael John Owen,Kelley Faber,Palmi V. Jonsson,Onofre Combarros,Michael Conlon O'Donovan,Laura B. Cantwell,Hilkka Soininen,Deborah Blacker,Simon Mead,Thomas H. Mosley,David A. Bennett,Tamara B. Harris,Laura Fratiglioni,Laura Fratiglioni,Clive Holmes,Renée F.A.G. de Bruijn,Peter Passmore,Thomas J. Montine,Karolien Bettens,Karolien Bettens,Jerome I. Rotter,Alexis Brice,Alexis Brice,Kevin Morgan,Tatiana Foroud,Walter A. Kukull,Didier Hannequin,John Powell,Mike A. Nalls,Karen Ritchie,Kathryn L. Lunetta,John S. K. Kauwe,Eric Boerwinkle,Eric Boerwinkle,Matthias Riemenschneider,Mercè Boada,Mikko Hiltunen,Eden R. Martin,Reinhold Schmidt,Dan Rujescu,Li-San Wang,Jean-François Dartigues,Jean-François Dartigues,Richard Mayeux,Christophe Tzourio,Albert Hofman,Markus M. Nöthen,Caroline Graff,Caroline Graff,Bruce M. Psaty,Bruce M. Psaty,Lesley Jones,Jonathan L. Haines,Peter Holmans,Mark Lathrop,Mark Lathrop,Margaret A. Pericak-Vance,Lenore J. Launer,Lindsay A. Farrer,Cornelia M. van Duijn,Christine Van Broeckhoven,Christine Van Broeckhoven,Valentina Moskvina,Sudha Seshadri,Julie Williams,Gerard D. Schellenberg,Philippe Amouyel,Philippe Amouyel,Philippe Amouyel +215 more
TL;DR: In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
Journal ArticleDOI
Alzheimer's Disease and Parkinson's Disease
TL;DR: The genetics of these familial forms of Alzheimer's and Parkinson's disease are examined to improve understanding of the pathobiology of the more common, sporadic forms of the diseases.
Journal ArticleDOI
Molecular pathophysiology of parkinson's disease
TL;DR: Increasing evidence indicates that deficits in mitochondrial function, oxidative and nitrosative stress, the accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system dysfunction may represent the principal molecular pathways or events that commonly underlie the pathogenesis of sporadic and familial forms of PD.
Journal Article
Analysis of human genetic linkage
M. Anne Spence,Susan E. Hodge +1 more
TL;DR: In this age of modern era, the use of internet must be maximized, as one of the benefits is to get the on-line analysis of human genetic linkage book, as the world window, as many people suggest.
Journal ArticleDOI
Epidemiology and etiology of Parkinson’s disease: a review of the evidence
Karin Wirdefeldt,Hans-Olov Adami,Hans-Olov Adami,Philip A. Cole,Dimitrios Trichopoulos,Jack S. Mandel +5 more
TL;DR: Studies that assessed possible shared etiological components between PD and other diseases show that REM sleep behavior disorder and mental illness increase PD risk and that PD patients have lower cancer risk, but methodological concerns exist.
References
More filters
Journal ArticleDOI
Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.
TL;DR: The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported, and these observations call into question current concepts of Parkinson's Disease as a single distinct morbid entity.
Journal ArticleDOI
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Journal ArticleDOI
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Tohru Kitada,Shuichi Asakawa,Nobutaka Hattori,Hiroto Matsumine,Yasuhiro Yamamura,Shinsei Minoshima,Masayuki Yokochi,Yoshikuni Mizuno,Nobuyoshi Shimizu +8 more
TL;DR: Mutations in the newly identified gene appear to be responsible for the pathogenesis of Autosomal recessive juvenile parkinsonism, and the protein product is named ‘Parkin’.
Journal ArticleDOI
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Mike Hutton,Corinne Lendon,Patrizia Rizzu,Matt Baker,Susanne Froelich,Susanne Froelich,Henry Houlden,Stuart Pickering-Brown,Sumitra Chakraverty,Adrian M. Isaacs,Andrew Grover,J. Hackett,Jennifer Adamson,Sarah Lincoln,Dennis W. Dickson,Peter Davies,Ronald C. Petersen,M. Stevens,E. De Graaff,E. Wauters,J. Van Baren,M. Hillebrand,Marijke Joosse,J. M. Kwon,Petra Nowotny,Lien Kuei Che,Joanne Norton,John C. Morris,L. A. Reed,John Q. Trojanowski,Hans Basun,Lars Lannfelt,M. Neystat,Stanley Fahn,Frances Dark,Tony Tannenberg,Peter R. Dodd,Nicholas K. Hayward,John B.J. Kwok,Peter R. Schofield,Athena Andreadis,Julie S. Snowden,David Craufurd,David Neary,F. Owen,Ben A. Oostra,John Hardy,Alison Goate,J. C. van Swieten,David M. A. Mann,Timothy Lynch,Peter Heutink +51 more
TL;DR: In this paper, the authors sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon in
Book
Analysis of Human Genetic Linkage
TL;DR: The first and still the only book of its kind, this volume offers a concise introduction to human genetic linkage analysis and gene mapping as discussed by the authors, as well as practical comments on available computer programs and websites.
Related Papers (5)
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism
Vincenzo Bonifati,Vincenzo Bonifati,Patrizia Rizzu,Marijke J. van Baren,Onno Schaap,Guido J. Breedveld,Elmar Krieger,Marieke C. J. Dekker,Ferdinando Squitieri,Pablo Ibanez,Marijke Joosse,Jeroen W.F. van Dongen,Nicola Vanacore,Nicola Vanacore,John C. van Swieten,Alexis Brice,Giuseppe Meco,Cornelia M. van Duijn,Ben A. Oostra,Peter Heutink +19 more