Genetics of Parkinson's disease

Area of Science:

• Neurogenetics
• Molecular Biology
• Neurology

Background:

• Familial aggregation and Mendelian inheritance patterns confirm a genetic basis for Parkinson's disease (PD).
• Specific gene loci and mutations, including alpha-synuclein and Parkin, have been identified in familial forms of PD.

Purpose of the Study:

• To review the established genetic contributions to Parkinson's disease etiology.
• To discuss identified genes and loci associated with familial Parkinsonian syndromes.
• To explore the potential of studying inherited PD to understand sporadic PD pathogenesis.

Main Methods:

• Review of case-control and twin studies demonstrating familial PD aggregation.
• Analysis of multigenerational families with Mendelian inheritance patterns.
• Genetic mapping and gene identification in familial Parkinsonian syndromes.

Main Results:

• A gene locus for autosomal dominant PD with Lewy bodies mapped to chromosome 4, linked to alpha-synuclein mutations.
• A gene for autosomal recessive juvenile parkinsonism (Parkin) mapped to chromosome 6, with distinct pathology.
• A third locus for dominant PD with Lewy bodies mapped to chromosome 2q13.

Conclusions:

• Current evidence does not directly link identified familial PD genes to the common sporadic form of PD.
• Elucidating molecular pathways in inherited PD is crucial for understanding the pathogenesis of sporadic neurodegenerative Parkinson's disease.