Home LiteratureArticle Details
PMID: 12169225 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

The genetics of Parkinson's disease.

Current neurology and neuroscience reports ·Vol. 2 ·No. 5 ·2002-09-00 ·Pages 439-46

Lim KL, Dawson VL, Dawson TM

Abstract

The recent identification of several genes and gene loci linked to familial forms of Parkinson's disease (PD) has contributed significantly to our understanding of the genetic contribution in PD. Although the etiology of sporadic PD remains unknown, it is currently assumed that genetic susceptibilities may be involved. The advent of genome-wide scanning techniques has now made it possible to conduct complete genome screens for linkage in PD in multigenerational parkinsonian kindreds. Such studies undoubtedly will be instrumental in establishing the susceptibility genes involved in idiopathic PD. This article reviews the recent advances in the genetics of PD.

MeSH Terms
Endopeptidases/genetics Humans Ligases/genetics Mutation Nerve Tissue Proteins/genetics Parkinson Disease/genetics Synucleins Ubiquitin Thiolesterase Ubiquitin-Protein Ligases
Chemicals
Nerve Tissue Proteins Synucleins USP12 protein, human Ubiquitin-Protein Ligases parkin protein Endopeptidases Ubiquitin Thiolesterase Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lim Kah Leong
Department of Neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Carnegie 214, Baltimore, MD 21287, USA.
Dawson Valina L
Dawson Ted M
References (46)
46 references, click to expand
  1. The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease.
    Neurosci Lett. 2000 Oct 27;293(2):127-30 PMID: 11027850
  2. Identifying genetic factors in Parkinson disease.
    JAMA. 2002 Feb 13;287(6):715-6 PMID: 11851532
  3. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36.
    Am J Hum Genet. 2001 Sep;69(3):629-34 PMID: 11462174
  4. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase.
    Nat Genet. 2000 Jul;25(3):302-5 PMID: 10888878
  5. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease.
    Nat Med. 2001 Oct;7(10 ):1144-50 PMID: 11590439
  6. Case-control study of the ubiquitin carboxy-terminal hydrolase L1 gene in Parkinson's disease.
    Neurology. 1999 Nov 10;53(8):1858-60 PMID: 10563640
  7. Complete genomic screen in Parkinson disease: evidence for multiple genes.
    JAMA. 2001 Nov 14;286(18):2239-44 PMID: 11710888
  8. Lewy bodies and parkinsonism in families with parkin mutations.
    Ann Neurol. 2001 Sep;50(3):293-300 PMID: 11558785
  9. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.
    Nat Genet. 1998 Feb;18(2):106-8 PMID: 9462735
  10. Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27.
    Am J Hum Genet. 1997 Mar;60(3):588-96 PMID: 9042918
  11. A chromosome 4p haplotype segregating with Parkinson's disease and postural tremor.
    Hum Mol Genet. 1999 Jan;8(1):81-5 PMID: 9887334
  12. The AS/AGU rat: a spontaneous model of disruption and degeneration in the nigrostriatal dopaminergic system.
    J Anat. 2000 May;196 ( Pt 4):629-33 PMID: 10923993
  13. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
    Nature. 1998 Apr 9;392(6676):605-8 PMID: 9560156
  14. Paralysis agitans of early onset with marked diurnal fluctuation of symptoms.
    Neurology. 1973 Mar;23(3):239-44 PMID: 4735177
  15. alpha-Synuclein gene haplotypes are associated with Parkinson's disease.
    Hum Mol Genet. 2001 Aug 15;10(17):1847-51 PMID: 11532993
  16. Genome-wide scan for Parkinson's disease: the GenePD Study.
    Neurology. 2001 Sep 25;57(6):1124-6 PMID: 11571351
  17. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.
    Science. 1997 Jun 27;276(5321):2045-7 PMID: 9197268
  18. Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease.
    Neuroreport. 1999 Feb 5;10 (2):427-9 PMID: 10203348
  19. Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.
    JAMA. 2001 Nov 14;286(18):2245-50 PMID: 11710889
  20. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease.
    Science. 2001 Jul 13;293(5528):263-9 PMID: 11431533
  21. The aetiology of idiopathic Parkinson's disease.
    Mol Pathol. 2001 Dec;54(6):369-80 PMID: 11724911
  22. Clinical features of parkinsonian patients with the alpha-synuclein (G209A) mutation.
    Mov Disord. 2001 Nov;16(6):1007-13 PMID: 11748731
  23. Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients.
    Neuroreport. 2000 Jul 14;11(10 ):2079-82 PMID: 10923647
  24. Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1.
    Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13354-9 PMID: 11078524
  25. A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1.
    Ann Neurol. 2002 Mar;51(3):296-301 PMID: 11891824
  26. Dopamine neuron agenesis in Nurr1-deficient mice.
    Science. 1997 Apr 11;276(5310):248-50 PMID: 9092472
  27. alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies.
    Proc Natl Acad Sci U S A. 1998 May 26;95(11):6469-73 PMID: 9600990
  28. Genetics of Parkinsonism: a review.
    Ann Hum Genet. 2001 Mar;65(Pt 2):111-26 PMID: 11427172
  29. Association between a polymorphism of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene and sporadic Parkinson's disease.
    Parkinsonism Relat Disord. 2000 Oct 1;6(4):195-197 PMID: 10900392
  30. PARK6-linked parkinsonism occurs in several European families.
    Ann Neurol. 2002 Jan;51(1):14-8 PMID: 11782979
  31. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase.
    Science. 1989 Nov 3;246(4930):670-3 PMID: 2530630
  32. Mutation, sequence analysis, and association studies of alpha-synuclein in Parkinson's disease.
    Neurology. 1998 Dec;51(6):1757-9 PMID: 9855543
  33. Parkin deletions in a family with adult-onset, tremor-dominant parkinsonism: expanding the phenotype.
    Ann Neurol. 2000 Jul;48(1):65-71 PMID: 10894217
  34. The ubiquitin pathway in Parkinson's disease.
    Nature. 1998 Oct 1 ;395(6701):451-2 PMID: 9774100
  35. Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate genes.
    Eur J Hum Genet. 2001 Sep;9(9):659-66 PMID: 11571553
  36. Increased susceptibility to sporadic Parkinson's disease by a certain combined alpha-synuclein/apolipoprotein E genotype.
    Ann Neurol. 1999 May;45(5):611-7 PMID: 10319883
  37. Association between early-onset Parkinson's disease and mutations in the parkin gene.
    N Engl J Med. 2000 May 25;342(21):1560-7 PMID: 10824074
  38. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.
    Science. 1993 Aug 13;261(5123):921-3 PMID: 8346443
  39. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity.
    J Biol Chem. 2000 Nov 17;275(46):35661-4 PMID: 10973942
  40. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin.
    Cell. 2001 Jun 29;105(7):891-902 PMID: 11439185
  41. Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36.
    Am J Hum Genet. 2001 Apr;68(4):895-900 PMID: 11254447
  42. Evaluation of 50 probands with early-onset Parkinson's disease for Parkin mutations.
    Neurology. 2002 Apr 23;58(8):1239-46 PMID: 11971093
  43. A candidate gene for human neurodegenerative disorders: a rat PKC gamma mutation causes a Parkinsonian syndrome.
    Nat Neurosci. 2001 Nov;4(11):1061-2 PMID: 11600890
  44. Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson's disease.
    Neurology. 2002 Mar 26;58(6):881-4 PMID: 11914402
  45. Prevalence of Parkinson's disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.
    Neurology. 2000;54(11 Suppl 5):S21-3 PMID: 10854357
  46. A susceptibility locus for Parkinson's disease maps to chromosome 2p13.
    Nat Genet. 1998 Mar;18(3):262-5 PMID: 9500549
Article Info
Journal
Current neurology and neuroscience reports
Abbr.
Curr Neurol Neurosci Rep
ISSN
1528-4042
DOI
10.1007/s11910-002-0071-9
Published
2002-09-00
Pages
439-46
Language
English
Region
United States
NLM ID
100931790
Subset
IM
Grants
NINDS NIH HHS · NS38377 · United States
External Links
PubMed source DOI: 10.1007/s11910-002-0071-9 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2