Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder with clinical features of bradykinesia, rigidity, resting tremor and postural instability resulting from the deficiency of dopamine in the nigrostriatal system. Previously we mapped a susceptibility gene for an autosomal dominant form of PD to a 10.6 cM region of chromosome 2p (PARK3; OMIM 602404). A common haplotype shared by two North American kindreds (Families B and C) genealogically traced to Southern Denmark and Northern Germany suggested a founder effect. Here we report progress in the refinement of the PARK3 locus and sequence analysis of candidate genes within the region. Members of families B and C were genotyped using polymorphic markers, reducing the minimum common haplotype to eight markers spanning a physical distance of 2.5 Mb. Analysis of 14 genes within the region did not reveal any potentially pathogenic mutations segregating with the disease, implying that none of these genes are likely candidates for PARK3.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Alcohol Oxidoreductases / genetics
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Amino Acid Transport Systems / genetics
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Chaperonins / genetics
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Chromosome Mapping
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Chromosomes, Human, Pair 2 / genetics*
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DNA / chemistry
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DNA / genetics
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DNA, Complementary / chemistry
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DNA, Complementary / genetics
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DNA-Binding Proteins / genetics
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Dynactin Complex
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Early Growth Response Transcription Factors
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Endosomal Sorting Complexes Required for Transport
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Family Health
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Female
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Genetic Predisposition to Disease / genetics*
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Genotype
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Haplotypes
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Humans
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Male
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Membrane Proteins / genetics
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Microsatellite Repeats
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Microtubule-Associated Proteins / genetics
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Nerve Tissue Proteins / genetics
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Nuclear Proteins / genetics
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Parkinson Disease / genetics*
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Pedigree
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Phosphoproteins / genetics
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Poly(A)-Binding Proteins
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Protein Tyrosine Phosphatases / genetics
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Proteins*
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RNA-Binding Proteins / genetics
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Receptors, Retinoic Acid / genetics
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Sequence Analysis, DNA
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T-Cell Intracellular Antigen-1
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Transcription Factors / genetics
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alpha-Glucosidases / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Amino Acid Transport Systems
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DNA, Complementary
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DNA-Binding Proteins
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DOK1 protein, human
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Dynactin Complex
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EGR4 protein, human
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Early Growth Response Transcription Factors
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Endosomal Sorting Complexes Required for Transport
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GAP-associated protein p62
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Membrane Proteins
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Phosphoproteins
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Poly(A)-Binding Proteins
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Proteins
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RNA-Binding Proteins
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Receptors, Retinoic Acid
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SEMA4F protein, human
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STAM protein, human
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T-Cell Intracellular Antigen-1
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TIA1 protein, human
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Transcription Factors
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DNA
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Alcohol Oxidoreductases
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sepiapterin reductase
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Protein Tyrosine Phosphatases
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glucosidase I
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alpha-Glucosidases
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Chaperonins