ISSN 1022-7954, Russian Journal of Genetics, 2006, Vol. 42, No. 8, pp. 858–871. © Pleiades Publishing, Inc., 2006.
Original Russian Text © Shadrina, Slominsky, 2006, published in Genetika, 2006, Vol. 42, No. 8, pp. 1045–1059.
Parkinson’s disease (idiopathic parkinsonism) is a
group of chronic progressive neurodegenerative dis-
eases, associated with defective functioning of basal
brain ganglia. This disease was ﬁrst described in 1817
by James Parkinson. Parkinson’s disease ranks second
in prevalence among neurodegenerative disorders after
Alzheimer’s disease. In most world populations, at
least 2–4% persons older than 65  and at least 1% of
persons older than 50 years of age  suffer from idio-
pathic parkinsonism. In recent years, an increase in the
number of people with Parkinson’s disease and a reduc-
tion in its age of onset have been observed .
The disease is steadily progressive and character-
ized by a classic tetrad of clinical symptoms: low-fre-
quency tremor at rest, rigidity of skeletal muscles of
hands and face (plastic hypertonus), low motor activity
(bradykinesia), and disturbance of movement coordina-
tion after sleep (postural instability). Neurodegenera-
tive changes are observed primarily in dopaminergic
neurons of the compact part of the substantia nigra,
basal nuclei, and tegmentum mesencephali. At later
stages of the disease, degeneration processes involve
also the cortex of the cerebral hemispheres .
Parkinson’s disease is characterized by the forma-
tion of the so-called Lewy bodies and Lewy neurites in
the bodies and branches of neurons. These eosinophilic,
ﬁlamentous intracellular inclusions consist of various
proteins, fatty acids, and polysaccharides. The basic
components of these inclusions are alpha-synuclein,
neuroﬁlament proteins, and ubiquitin [5, 6]. In addi-
tion, gliosis often is observed in the striatum and the
substantia nigra of Parkinson’s disease patients 
The familial form of Parkinson’s disease has been
ﬁrst described in the early 20th century. To date, 10–
15% of patients are thought to have positive family
anamnesis . However, in most patients the disease is
sporadic and determined by complex interaction
between genetic and environmental factors. The combi-
nation of a similar genetic background and life style
increases the risk of the disease in relatives of patients
by a factor of 2 to 7 .
OF PARKINSON’S DISEASE
State of the Art of Mapping of Genes
for Parkinson’s Disease
To date, 11 loci for monogenic forms of Parkinson’s
disease have been mapped in the human genome. Only
a few of them are responsible for the development of
the disease in a relatively high number (more than ten)
of families. The mapped loci and precisely identiﬁed
genes, whose mutations are related to the development
of familial parkinsonism, are listed in the table.
Based on analysis of these loci and genes, three
groups of metabolic processes were identiﬁed, distur-
bance of which may cause parkinsonism. These pro-
cesses are associated with ubiquitin-dependent protea-
somal degradation of proteins, differentiation of
dopaminergic neurons, and mitochondrial dysfunction.
Genes Associated with Ubiquitin-Dependent
Proteasomal Protein Degradation
Historically, the ﬁrst described locus of familial Par-
kinson’s disease was
mapped to chromosome
4q21. This locus was revealed in a family of the Italian
American origin with autosomal dominant Parkinson’s
disease characterized by an early onset and rapid pro-
gression of the condition . It was shown that the
development of the disease was determined by the mis-
in the alpha-synuclein gene.
The same mutation was found in a Greek family .
Molecular Genetics of Parkinson’s Disease
M. I. Shadrina and P. A. Slominsky
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182 Russia;
fax: (495) 196-02-21; e-mail: email@example.com
Received February 22, 2006
—The current views on the role of genetic factors in the pathogenesis of Parkinson’s disease are con-
sidered. The review is focused on monogenic forms of the disease, for which 11 loci are mapped and seven
genes whose mutations cause the disease are identiﬁed. In addition, a number of candidate genes for sporadic
Parkinson’s disease are described. The further development of studying genetic bases of Parkinson’s disease
will follow two main directions: in-depth analysis of genes related to the monogenic form of the disease and
more large-scale associative investigation of candidate genes for the sporadic form of Parkinson’s disease.