Genetic Analysis Of Parkinsonism And Parkinson's Disease

Hardy, John A.

Abstract

Although Parkinson's disease has been considered the archetypal non-genetic disorder, recent analysis has shown that it is, in fact, at least partly genetic in origin with variability in 3 genes (synuclein, parkin and ubiqutin hydrolase)known to be associated with the disease and 7 genetic linkages identified but not resolved. Our work, in collaboration with the Bob Nussbaum (NHGRI) and with Katrina Gwinn-Hardy (Fischbeck lab: NINDS). We are working on collecting families with Parkinson's disease and carrying out genetic analysis of known genes and will be carrying out linkage analysis and positional cloning to try and identify new loci for this prevalent disorder. One surprising feature of our work has been that we have found that spinocerebellar ataxias can masquerade as Parkinson's disease in African and Asian populations. Last year, we have made an extremely important finding: that some cases of Parkinson's disease are caused by a chromosomal abnormality which causes a triplication ofthe synuclein gene. Others have confirmed this. This finding implicates the synuclein protein in the cell death process of all cases of Parkinson's disease. This year, we showed that a consequence of that finding was that individuals with the mitation had double their blood synuclein levels.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Aging (NIA)
• Type: Intramural Research (Z01)
• Project #: 1Z01AG000952-04
• Application #: 7135611
• Study Section: (LNG)
• Support Year: 4
• Fiscal Year: 2005

Institution

• Name: Aging
• Country: United States

Publications

Hardy, John (2006) No definitive evidence for a role for the environment in the etiology of Parkinson's disease. Mov Disord 21:1790-1

Fidani, Liana; Kalinderi, Kallirhoe; Bostantjopoulou, Sevasti et al. (2006) Association of the Tau haplotype with Parkinson's disease in the Greek population. Mov Disord 21:1036-9

Fung, Hon-Chung; Chen, Chiung-Mei; Hardy, John et al. (2006) Lack of G2019S LRRK2 mutation in a cohort of Taiwanese with sporadic Parkinson's disease. Mov Disord 21:880-1

Clarimon, Jordi; Scholz, Sonja; Fung, Hon-Chung et al. (2006) Conflicting results regarding the semaphorin gene (SEMA5A) and the risk for Parkinson disease. Am J Hum Genet 78:1082-4; author reply 1092-4

Hernandez, Dena; Paisan Ruiz, Coro; Crawley, Anthony et al. (2005) The dardarin G 2019 S mutation is a common cause of Parkinson's disease but not other neurodegenerative diseases. Neurosci Lett 389:137-9

Hardy, John; Lees, Andrew J (2005) Parkinson's disease: a broken nosology. Mov Disord 20 Suppl 12:S2-4

Miller, David W; Crawley, Anthony; Gwinn-Hardy, Katrina et al. (2005) Unaltered alpha-synuclein blood levels in juvenile Parkinsonism with a parkin exon 4 deletion. Neurosci Lett 374:189-91

Martinez, Maria; Brice, Alexis; Vaughan, Jenny R et al. (2005) Apolipoprotein E4 is probably responsible for the chromosome 19 linkage peak for Parkinson's disease. Am J Med Genet B Neuropsychiatr Genet 136:72-4

Hardy, J (2005) Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: 'permissive templating' as a general mechanism underlying neurodegeneration. Biochem Soc Trans 33:578-81

McInerney-Leo, Aideen; Hadley, Donald W; Gwinn-Hardy, Katrina et al. (2005) Genetic testing in Parkinson's disease. Mov Disord 20:1-10