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Summary of "PARK" Loci and of linkage regions implied by Genome-wide linkage analysis
Back Search Methods Disclaimer Credits
Chromosome PARK-Locusa Initial Study
4q21-q23 PARK1a Polymeropoulos, 1996
6q25.2-q27 PARK2 Matsumine, 1997
2p13 PARK3 Gasser, 1998
4p14-16.3 PARK4a Farrer, 1999
4p14 PARK5 Leroy, 1998
1p35-p36 PARK6 Valente, 2001
1p36.33 - p36.12 PARK7 van Duijn, 2001
12p11.23-q13.11 PARK8 Funayama, 2002
1p36 PARK9 Hampshire, 2001
1p32 PARK10 Hicks, 2002
2q36-q37 PARK11 Pankratz, 2003
Xq21-q25 PARK12 Pankratz, 2003
2p12 PARK13 Strauss, 2005
18q11 PARK14 Gao, 2009
22q12-q13 PARK15 Shojaee, 2008
1q32 PARK16 Satake, 2009

Table 1. Overview of genetic (“PARK”) loci associated with a monogenetic form of PD or related disorders. The table summarizes the chromosomal locations of the “PARK” loci as defined in the OMIM (Online Mendelian Inheritance in Man) database. The approximate chromosomal intervals of these loci is indicated by a green line on the respective chromosome graphs throughout PDGene (example). Note that not all loci were necessarily implied by linkage analysis, and not all loci were identified using PD as phenotype.

aNote that PARK1 and PARK4 were initially assigned to different regions on chromosome 4, but were later ascribed to the same underlying locus.

Chromosome Location (cM) Previous Studies
1p35-32 58-87 Hicks (2002)
1p32-31 87-116 n.a.
2p13-q13 89-120 Martinez (2004)
2q13-22 120-149 n.a.
2q31-35 179-209 Pankratz (2002)
5q21-31 113-141 Hicks (2002)
5q23-35 132-198 Scott (2001), Martinez (2004)
8p23-22 0-28 Scott (2001)
9q31-34 112-169 DeStefano (2001)
14q32 110-138 n.a.

Table 2. Summary of the genetic loci showing evidence for linkage in the meta-analysis of whole-genome scans by Rosenberger et al. (2007). Linkage regions highlighted here are based on the results summarized in Table 2 of that paper. Meta-analysis (using the Genome Search Meta-Analysis [GSMA] method) was applied to data from a total of five whole-genome linkage scans published at the time across 862 families with 1384 affected subjects. Studies investigating Parkinsonian syndromes other than PD or analyzing overlapping samples were excluded. For the meta-analysis, DNA markers were allocated into bins of 30 cM and 60 cM. The approximate chromosomal intervals of the loci showing nominal significant linkage are indicated by a red line on the respective chromosome graphs throughout PDGene (example)."Previous studies" refers to the publication included in Rosenberger et al (2007) that previously reported a particular region to show evidence for genetic linkage ("n.a." indicates regions for which no individual study reported linkage prior to the meta-analysis). Please consult the paper by Rosenberger et al. (2007) for more details.

Note that studies published after 2004 were not included in the meta-analysis. Since then, additional whole genome linkage screens have been performed (e.g. Foltynie, 2005; Krygowska-Wajs, 2005; Gao, 2009) some of which replicated the putative PD linkage regions above (e.g. 1p31 and 5q23), or suggested new loci (e.g. 3q25; Gao, 2009) that require further replication and meta-analysis.

References

DeStefano AL, Golbe LI, et al. (2001).”Genome-wide scan for Parkinson's disease: the GenePD Study.” Neurology 57(6):1124-6.

Farrer, M, Gwinn-Hardy, et al. (1999). “A chromosome 4p haplotype segregating with Parkinson's disease and postural tremor.” Hum Molec Genet 8: 81-85.

Foltynie T, Hicks A, et al. (2005). “A genome wide linkage disequilibrium screen in Parkinson's disease.” J Neurol 252(5):597-602.

Funayama M, Hasegawa K, et al. (2002). “A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1.” Ann Neurol 51(3):296-301.

Gasser T, Muller-Myhsok B, et al. (1998). “A susceptibility locus for Parkinson's disease maps to chromosome 2p13.” Nat Genet 18(3):262-5.

Gao X, Martin ER, et al. (2009). ”Genome-wide linkage screen in familial Parkinson disease identifies loci on chromosomes 3 and 18.” Am J Hum Genet 84(4):499-504.

Hampshire DJ, Roberts E, et al. (2001). “Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36.” J Med Genet 38(10):680-2.

Hicks AA, Petursson H, et al.(2002)” A susceptibility gene for late-onset idiopathic Parkinson's disease.” Ann Neurol 52(5):549-55.

Krygowska-Wajs A, Kachergus JM, et al. (2005). “Clinical and genetic evaluation of 8 Polish families with levodopa-responsive parkinsonism.” J Neural Transm 112(11):1487-502.

Leroy E, Boyer R, et al. (1998). “The ubiquitin pathway in Parkinson's disease.” Nature 395(6701):451-2.

Martinez M, Brice A, et al. (2004). “Genome-wide scan linkage analysis for Parkinson's disease: the European genetic study of Parkinson's disease.” J Med Genet 41(12):900-7.

Matsumine H, Saito M, et al. (1997). “Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27.” Am J Hum Genet 60(3):588-96.

Pankratz N, Nichols WC, et al. (2002). “Genome screen to identify susceptibility genes for Parkinson disease in a sample without parkin mutations.” Am J Hum Genet 71(1):124-35.

Pankratz N, Nichols WC, et al. (2003). “Significant linkage of Parkinson disease to chromosome 2q36-37.” Am J Hum Genet 72(4):1053-7.

Pankratz N, Nichols WC, et al. (2003). “Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families.” Hum Mol Genet 12(20):2599-608.

Polymeropoulos MH, Higgins JJ, et al. (1996). “Mapping of a gene for Parkinson's disease to chromosome 4q21-q23.” Science 274(5290):1197-9.

Rosenberger A, Sharma M, et al. (2007). “Meta analysis of whole-genome linkage scans with data uncertainty: an application to Parkinson's disease.” BMC Genet 2;8:44.

Scott WK, Nance MA, et al. (2001). “Complete genomic screen in Parkinson disease: evidence for multiple genes.” JAMA 286(18):2239-44.

Shojaee S, Sina F, et al. (2008). “Genome-wide linkage analysis of a Parkinsonian-pyramidal syndrome pedigree by 500 K SNP arrays.” Am J Hum Genet 82(6):1375-84.

Strauss KM, Martins LM, et al. (2005). “Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease.” Hum Mol Genet 14(15):2099-111.

Valente EM, Bentivoglio AR, et al. (2001). “Localization of a novel locus for autosomal recessive early-onset Parkinsonism, PARK6, on human chromosome 1p35-p36.” Am J Hum Genet 68(4):895-900.

van Duijn CM, Dekker MC, et al. (2001). “Park7, a novel locus for autosomal recessive early-onset Parkinsonism, on chromosome 1p36.” Am J Hum Genet 69(3):629-34.

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