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. 2004 Jan;74(1):11-9.
doi: 10.1086/380647. Epub 2003 Dec 19.

The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval

Alexander Zimprich  1 , Bertram Müller-Myhsok, Matthew Farrer, Petra Leitner, Manu Sharma, Mary Hulihan, Paul Lockhart, Audrey Strongosky, Jennifer Kachergus, Donald B Calne, Jon Stoessl, Ryan J Uitti, Ronald F Pfeiffer, Claudia Trenkwalder, Nikolaus Homann, Erwin Ott, Karoline Wenzel, Friedrich Asmus, John Hardy, Zbigniew Wszolek, Thomas Gasser
Affiliations

The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval

Alexander Zimprich et al. Am J Hum Genet. 2004 Jan.

Erratum in

  • Am J Hum Genet. 2004 Sep;75(3):534

Abstract

Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been identified in one large Japanese family. Linkage has been shown to a 16-cM centromeric region of chromosome 12, between markers D12S1631 and D12S339. We tested 21 white families with Parkinson disease and an inheritance pattern compatible with autosomal dominant transmission for linkage in this region. Criteria for inclusion were at least three affected individuals in more than one generation. A total of 29 markers were used to saturate the candidate region. One hundred sixty-seven family members were tested (84 affected and 83 unaffected). Under the assumption of heterogeneity and through use of an affecteds-only model, a maximum multipoint LOD score of 2.01 was achieved in the total sample, with an estimated proportion of families with linkage of 0.32. This LOD score is significant for linkage in a replication study and corresponds to a P value of.0047. Two families (family A [German Canadian] and family D [from western Nebraska]) reached significant linkage on their own, with a combined maximum multipoint LOD score of 3.33, calculated with an affecteds-only model (family A: LOD score 1.67, P=.0028; family D: LOD score 1.67, P=.0028). When a penetrance-dependent model was calculated, the combined multipoint LOD score achieved was 3.92 (family A: LOD score 1.68, P=.0027; family D: LOD score 2.24, P=.0007). On the basis of the multipoint analysis for the combined families A and D, the 1-LOD support interval suggests that the most likely disease location is between a CA repeat polymorphism on genomic clone AC025253 (44.5 Mb) and marker D12S1701 (47.7 Mb). Our data provide evidence that the PARK8 locus is responsible for the disease in a subset of families of white ancestry with autosomal dominant parkinsonism, suggesting that it could be a more common locus.

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Figures

Figure 1
Figure 1
Linkage analysis of all 21 pedigrees with autosomal dominant Parkinson disease. Affecteds-only multipoint LOD scores are summed across families.
Figure 2
Figure 2
Pedigree structure of families A and D. Blackened symbols denote affected family members, and asterisks (*) indicate individuals typed with polymorphic markers. For clarity, only part of each pedigree is shown. The complete pedigrees with detailed clinical descriptions are shown elsewhere (Wszolek and Markopoulou 1999).
Figure 3
Figure 3
Multipoint LOD score plots for families A and D. The X-axis represents location in centimorgans, and the Y-axis represents LOD scores. LOD scores are shown for family A, family D, and both families combined (A+D). a, Affected-only model. b, Penetrance-dependent model.
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References

Electronic-Database Information

    1. Genetic Location Database, http://cedar.genetics.soton.ac.uk/public_html/ldb.html
    1. MAP-O-MAT, http://compgen.rutgers.edu/mapomat/ (for marker information)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for parkinsonism, PARK1, FTDP-17, PARK2, PARK5, PARK7, and PARK8)
    1. UCSC Human Genome Browser, Human Genome Working Draft, http://genome.ucsc.edu/goldenPath/septTracks.html (for new polymorphic markers, developed by searching the database for CA repeats using in silico BAC sequence)

References

    1. Bonifati V, Rizzu P, Van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, Van Dongen JW, Vanacore N, Van Swieten JC, Brice A, Meco G, Van Duijn CM, Oostra BA, Heutink P (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256–25910.1126/science.1077209 - DOI - PubMed
    1. Bugiani O, Giaccone G, Piccardo P, Morbin M, Tagliavini F, Ghetti B (2000) Neuropathology of Gerstmann-Straussler-Scheinker disease. Microsc Res Tech 50:10–1510.1002/1097-0029(20000701)50:1<10::AID-JEMT3>3.3.CO;2-Y - DOI - PubMed
    1. Calne DB, Snow BJ, Lee C (1992) Criteria for diagnosing Parkinson’s disease. Ann Neurol Suppl 32:S125–S127 - PubMed
    1. Daniel SE, Lees AJ (1993) Parkinson’s Disease Society Brain Bank, London: overview and research. J Neural Transm Suppl 39:165–172 - PubMed
    1. de Rijk MC, Tzourio C, Breteler MM, Dartigues JF, Amaducci L, Lopez Pousa S, Manubens Bertran JM, Alperovitch A, Rocca WA (1997) Prevalence of parkinsonism and Parkinson’s disease in Europe. J Neurol Neurosurg Psychiatry 62:10–15 - PMC - PubMed

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