Identifying PD-causing genes and genetic susceptibility factors: current approaches and future prospects.
Over the last years, a plethora of genetic findings have completely changed our views on the aetiology of Parkinson's disease (PD). Linkage studies and positional cloning strategies have identified mutations in a growing number of genes which cause monogenic autosomal-dominant or autosomal-recessive forms of the disorder. While these Mendelian forms of PD are relatively rare, high-throughput genotyping and sequencing technologies have more recently provided evidence that low-penetrance variants in at least some of these genes also play a direct role in the aetiology of the common sporadic disease. In addition, rare variants in other genes, such as the Gaucher's disease-associated glucocerebrosidase A, have also been found to be important risk factors at least in subgroups of patients. Thus, an increasingly complex network of genes contributing in different ways to disease risk and progression is emerging. These findings provide the 'genetic entry points' to identify molecular targets and readouts necessary to design rational disease-modifying treatments.
Gasser
Thomas
T
Hertie Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, Tübingen, Germany. Thomas.gasser@uni-tuebingen.de
D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005962:Glucosylceramidase / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008969:Molecular Sequence Data; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D020734:Parkinsonian Disorders / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
D005962:Glucosylceramidase; D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D016875:tau Proteins; D000099202:PTEN-Induced Putative Kinase; C054369:MAPT protein, human; C497604:SNCA protein, human; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human