Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…SNCA (also known as PARK1) was the first gene identified in a large Italian family (Contursi kindred) segregating a pathogenic missense mutation -A53T -causing dominantly inherited PD and LB pathology [38,39]. Since then, two groups of diseaseͲcausing mutations have been Predominantly localized to presynaptic nerve terminals, alphaͲsyn can also be found in other neuronal compartments like the cytosol, mitochondriaand nucleus.…”

Implications of gene copy-number variation in health and diseases

“…It is found to affect 1% of the population over 50 years of age. 12 A novel triplication in SNCA gene, located on 4q21 is found to be linked to autosomal dominant PD and showed the dosage effect. Further, the gene expression profiling reflected an approximately twofold increase of SNCA protein in blood, mRNA in the brain tissue and also the deposition of large aggregates of this protein in the brain tissue.…”

Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra

“…Parkinson's disease (PD) is the second most common neurodegenerative disorder of adult onset after Alzheimer's disease (AD), and affects between 1 and 2% of the population over the age of 65 [14,20,54]. The vast majority of clinical PD cases are sporadic.…”

“…The vast majority of clinical PD cases are sporadic. Studies of rare familial forms of PD have so far led to the identification of six genes in which mutations can cause PD [4,17,34,36,37,40,54,55,60,65,66,72]. The products of these genes are alpha-synuclein (SNCA), parkin (ubiquitin-conjugating enzyme; UBCH7; PARK2), ubiquitin Cterminal hydrolase L1 (UCHL1), PTEN-induced kinase 1 (PINK), DJ-1 and leucine-rich repeat kinase 2 (LRRK2).…”