Significant Linkage of Parkinson Disease to Chromosome 2q36-37

Pankratz, Nathan; Nichols, William C.; Uniacke, Sean K.; Halter, Cheryl; Rudolph, Alice; Shults, Cliff; Conneally, P. Michael; Foroud, Tatiana; Golbe, Lawrence I.; Koller, William C.; Lyons, Kelly E.; Marder, Karen; Marshall, Frederick J.; Oakes, David; Shinaman, Aileen; Siemers, Eric; Wojcieszek, Joanne; Belden, Joann; Carter, Julie; Camicioli, Richard; Andrews, Pamela; Fernandez, Magali; Hubble, Jean; Reider, Carson; Rajput, Ali H.; Rajput, Alex; Shirley, Theresa; Panisset, Michel; Hall, Jean; Mendis, Tilak; Grimes, David A.; Gray, Peggy; Ramos, Carmen Serrano; Roque, Sandra; Reich, Stephen G.; Dunlop, Becky; Hauser, Robert A.; Sanchez‐Ramos, Juan; Zesiewicz, Theresa; Delgado, Holly; Friedman, Joseph H.; Fernández, Hubert H.; Lannon, Margaret C.; Seeberger, Lauren; O’Brien, Christopher J.; Judd, Deborah; Elmer, Lawrence; Davis, Kathy; Fontaine, Deborah; Pfeiffer, Ronald F.; Pfeiffer, Brenda; Aminoff, Michael J.; DiMinno, Mariann; Truong, Daniel; Pathak, Mayank; Tran, Anhoa; Rodnitzky, Robert L.; Dobson, Judith; Pahwa, Rajesh; Thomas, Stephanie; Jennings, Danna; Marek, Kenneth; Mendick, Susan; Harris, Juliette; Weiner, William J.; Kurlan, Roger; Berry, Debra; LeWitt, Peter A.; DeAngelis, Maryan; Tuite, Paul J.; Schacherer, Robyn; Martin, W. R. Wayne; Wieler, Marguerite; Manyam, Bala V.; Simpson, Patricia; Bertoni, John M.; Peterson, Carolyn; Gordon, Mark Forrest; Hamann, Joanna; Jankovic, Joseph; Hunter, Christine; Factor, Stewart A.; Evans, Sharon; Nieves, Anette; So, Julie; Stacy, Mark; Williamson, Kelli; Walker, Francis O.; Hunt, Victoria; Kang, Un Jung; Uy, Shirley; Blindauer, Karen; Petit, Jeannine; Simon, David K.; Scollins, Lisa; Pullman, Rachel Saunders; Boyar, Karyn; Gordon, Paul H.; Werner, Joan Stehle

doi:10.1086/374383

Cited by 147 publications

(69 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These mutations may account for PD in as many as 50% of familial cases of autosomal recessive juvenile parkinsonism [45,46]. Clinically, the disease usually begins when the patient is in his/her 20s, and is prominently associated with dystonia and diurnal fluctuations, progressing slowly while accompanied by early and severe levodopa-induced dyskinesis, but no dementia.…”

Section: Parkin Genementioning

confidence: 99%

Biomarkers of neurodegenerative disorders: How good are they?

Rachakonda

Pan

2004

Cell Res

View full text Add to dashboard Cite

Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies, biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differential between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance, are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated β-amyloid peptide for Alzheimer's disease (AD), α-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson's disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington's gene mutations in Huntington's disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.

show abstract

Section: Parkin Genementioning

confidence: 99%

Biomarkers of neurodegenerative disorders: How good are they?

Rachakonda

Pan

2004

Cell Res

View full text Add to dashboard Cite

show abstract

“…The products of these genes are alpha-synuclein (SNCA), parkin (ubiquitin-conjugating enzyme; UBCH7; PARK2), ubiquitin Cterminal hydrolase L1 (UCHL1), PTEN-induced kinase 1 (PINK), DJ-1 and leucine-rich repeat kinase 2 (LRRK2). Additional loci harbouring presumptive PD genes have been mapped including PARK3 [19], PARK10 [24] and PARK11 [51].…”

Section: Introductionmentioning

confidence: 99%

Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra

et al. 2007

View full text Add to dashboard Cite

The identification of mutations that cause familial Parkinson's disease (PD) provides a framework for studies into pathways that may be perturbed also in the far more common, non-familial form of the disorder. Following this hypothesis, we have examined the gene regulatory network that links alpha-synuclein and parkin pathways with dopamine metabolism in neuropathologically verified cases of sporadic PD. By means of an in silico approach using a database of eukaryotic molecular interactions and a whole genome transcriptome dataset validated by qRT-PCR and histological methods, we found parkin and functionally associated genes to be upregulated in the lateral substantia nigra (SN). In contrast, alpha-synuclein and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene expression levels were significantly reduced in both the lateral and medial SN in PD. Gene expression for Septin 4, a member of the GTP-binding protein family involved in alpha-synuclein metabolism was elevated in the lateral parkinsonian SN. Additionally, catalase and mitogen-activated protein kinase 8 and poly (ADP-ribose) polymerase family member 1 (PARP1) known to function in DNA repair and cell death induction, all members of the dopamine synthesis pathway, were up-regulated in the lateral SN. In contrast, two additional PD-linked genes, glucocerebrosidase and nuclear receptor subfamily 4, group A, member 2 (NR4A2) showed reduced expression. We show that in sporadic PD, parkin, alpha-synuclein and dopamine pathways are co-deregulated. Alpha-synuclein is a member of all three gene regulatory networks. Our analysis results support the view that alpha-synuclein has a central role in the familial as well as the non-familial form of the disease and provide steps towards a pathway definition of PD.

show abstract

“…17 An additional study was performed using a subset of the previous, but expanded sample, which included only pedigrees with a strong family history of PD: in an analysis of 65 families (77 sibling pairs) a maximum LOD score of 5.1 at the marker D2S206 on chromosome 2q36-37 was found using an autosomal dominant model of disease transmission. 18 Recently, Pankratz et al 19 confirmed their previous results using a further enlarged sample of 85 families (113 sibling pairs) with a strong family history of PD: they again reported a linkage to the 2q36 -37 region (LOD score 4.9).…”

Section: Introductionmentioning

confidence: 69%

“…The inclusion of the families with parkin mutations resulted in a higher LOD score, but the LOD score remained clearly significant in the sample without parkin mutations. 18,19 We repeated our linkage analysis excluding nine families, in which we could not rule out linkage to marker D6S305 in the parkin gene. Excluding these families did not change our overall results, indicating that there is no specific contribution of this subset of families to our results.…”

Section: Discussionmentioning

confidence: 99%

PARK11 is not linked with Parkinson's disease in European families

et al. 2004

View full text Add to dashboard Cite

Parkinson's disease (PD) is a genetically heterogeneous disease. Recently, significant linkage has been reported to a 39.5 cM region on the long arm of chromosome 2 (2q36-37; PARK11) in North American Parkinson families under an autosomal dominant model of inheritance. We have performed a replication study to confirm linkage to this region in a European population. Linkage analysis in 153 individuals from 45 European families with a strong family history of PD did not show any significant LOD score in this region. Therefore, PARK11 does not seem to play a major role for familial PD in the European population.

show abstract

Significant Linkage of Parkinson Disease to Chromosome 2q36-37

Cited by 147 publications

References 19 publications

Biomarkers of neurodegenerative disorders: How good are they?

Biomarkers of neurodegenerative disorders: How good are they?

Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra

PARK11 is not linked with Parkinson's disease in European families

Contact Info

Product

Resources

About