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Milestones in PD genetics
Author(s) -
Gasser Thomas,
Hardy John,
Mizuno Yoshikuni
Publication year - 2011
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.23637
Subject(s) - mendelian inheritance , disease , genetics , penetrance , positional cloning , glucocerebrosidase , biology , etiology , multifactorial inheritance , genetic linkage , genetic association , gene , bioinformatics , medicine , phenotype , genotype , pathology , single nucleotide polymorphism
Over the last 25 years, genetic findings have profoundly changed our views on the etiology of Parkinson's disease. Linkage studies and positional cloning strategies have identified mutations in a number of genes that cause several monogenic autosomal‐dominant or autosomal‐recessive forms of the disorder. Although most of these Mendelian forms of Parkinson's disease are rare, whole‐genome association studies have more recently provided convincing evidence that low‐penetrance variants in at least some of these, but also in several other genes, play a direct role in the etiology of the common sporadic disease as well. In addition, rare variants with intermediate‐effect strengths in genes such as Gaucher's disease–associated glucocerebrosidase A have been discovered as important risk factors. “Next‐generation” sequencing technologies are expected by some to identify many more of these variants. Thus, an increasingly complex network of genes contributing in different ways to disease risk and progression is emerging. These findings may provide the “genetic entry points” to identify molecular targets and readouts necessary to design rational disease‐modifying treatments. © 2011 Movement Disorder Society